Cancer Epidemiology - Articles in Press

Comparison of breast density measured by dual energy X-ray absorptiometry with mammographic density among adult women in Hawaii - Uncorrected Proof

2010-07-26

Abstract: While use of mammography is limited, due to concerns related to radiation exposure, dual energy X-ray absorptiometry (DXA), commonly available in medical care settings, is characterized by low radiation exposure. In the current paper, we compared breast density measured by DXA with mammographic density in 101 adult women who had a screening mammogram during the last 2 years. DXA scans of both breasts were taken using a clinical DXA system calibrated to measure breast density. The total projected breast area was manually delineated on each image and percent fibroglandular volume density (%FGV), absolute fibroglandular volume, total breast area and volume were computed. After digitizing mammographic films, total breast area, dense area, and percent density (PD) were estimated using computer-assisted mammographic density assessment. Both DXA and mammographic measures showed high correlations between left and right breasts ranging from 0.85 to 0.98 (p<0.0001). Mean %FGV was 38.8±14.3%, and mean percent density was 31.9±18.2% for craniocaudal views and 28.3±16.2% for mediolateral views. The correlation between the two measures was 0.76 for both views (p<0.0001). Associations with common risk factors showed similar patterns for DXA and mammographic densities; in particular, the inverse associations with BMI and age at menarche were evident for both methods. Multilinear regression with stepwise selection indicated an explained variance of 0.56 for %FGV alone and of 0.58 for %FGV plus number of children. Despite some differences in methodology, the current comparison suggests that DXA may provide a low-radiation option in evaluating breast density.

Investigating reasons for socioeconomic inequalities in breast cancer survival in New Zealand - Uncorrected Proof

Fiona McKenzie, Lis Ellison-Loschmann, Mona Jeffreys — 2010-07-26

Abstract: Background: This study investigated the role that demographic and tumour factors play in explaining socioeconomic inequalities in breast cancer survival. Methods: Breast cancer cases notified to the New Zealand Cancer Registry (NZCR) from April 2005 to April 2007 were followed up to April 2009. The New Zealand area-based deprivation index (NZDep) was used as a measure of socioeconomic position. Relative survival rates were estimated using sex-, deprivation- and ethnic-specific life tables. Multiple imputation was used to impute missing data. Excess mortality modelling was used to estimate the contribution of demographic and tumour factors to inequalities in survival. Results: There were 2968 breast cancer cases included and 433 recorded deaths. Relative survival rates at 4 years varied across deprivation groups. Using NZDep deciles 1–4 (least deprived) as the reference group, the age- and ethnicity-adjusted hazard ratio (HR) for NZDep deciles 7–8 was 2.03 (CI 1.36–3.04) and for NZDep deciles 9–10 was 1.93 (CI 1.28–2.92). In the fully adjusted model there remained 50% excess mortality for the two most deprived groups compared to the most affluent. Variables which measured timely access to care (extent/size) accounted for more of the survival disparity than breast cancer subtype variables (ER/PR/HER2). Conclusion: Women from deprived areas in New Zealand who are diagnosed with breast cancer are less likely to survive as long as those from affluent areas. A substantial proportion of these socioeconomic disparities can be attributed to differential access to health care although other factors, currently unknown, are also likely to play an important role.

Intake of dietary fats and colorectal cancer risk: Prospective findings from the UK Dietary Cohort Consortium - Uncorrected Proof

2010-07-26

Abstract: Introduction: Epidemiologic evidence for an association between colorectal cancer (CRC) risk and total dietary fat, saturated fat (SF), monounsaturated fat (MUFA) and polyunsaturated fat (PUFA) is inconsistent. Previous studies have used food frequency questionnaires (FFQ) to assess diet, but data from food diaries may be less prone to severe measurement error than data from FFQ. Methods: We conducted a case–control study nested within seven prospective UK cohort studies, comprising 579 cases of incident CRC and 1996 matched controls. Standardized dietary data from 4- to 7-day food diaries and from FFQ were used to estimate odds ratios for CRC risk associated with intake of fat and subtypes of fat using conditional logistic regression. We also calculated multivariate measurement error corrected odds ratios for CRC using repeated food diary measurements. Results: We observed no associations between intakes of total dietary fat or types of fat and CRC risk, irrespective of whether dietary data were obtained using food diaries or FFQ. Conclusion: Our results do not support the hypothesis that intakes of total dietary fat, SF, MUFA or PUFA are linked to risk of CRC.

The role of the doctor and the medical system in the diagnostic delay in pediatric malignancies - Uncorrected Proof

Motti Haimi, Monique Perez-Nahum, Nili Stein, Myriam Weyl Ben Arush — 2010-07-26

Abstract: Aim: We evaluated the roles of the doctor and the medical system in Israel in the diagnostic delay of childhood malignancies. Methods: We investigated the factors affecting the delay in the diagnosis of childhood malignancies in 315 children with solid malignancies, diagnosed and treated in Rambam Medical Center (RMC), between 1993 and 2001. Those factors were divided into two groups: ‘Healthcare-system-related parameters’, (factors directly related to the medical system), and ‘Patient-related parameters’ (factors that are not part of the medical system, but directly affect medical judgment and decisions, including factors related to the tumor). We also took into consideration epidemiological, social, and medical issues. Results: The main ‘Healthcare-system-related parameters’, which were found to influence the delay in diagnosis, were the type of medical authority that was initially consulted; the specialty of the first doctor; the number of additional doctors whom the child had visited, and the number of times the child had visited the first doctor. The main ‘Patient-related parameters’ found to have an impact on the delay in diagnosis were the age of the child, the tumor type, and the presenting symptom. Conclusions: The education and awareness of doctors at the primary healthcare clinics must be improved. We suggest ways of improving the approach of doctors and managing a child with a suspected malignancy.

The impact of menopausal hormone therapy on the incidence of different breast cancer types––Data from the Cancer Registry Hamburg 1991–2006 - Uncorrected Proof

2010-07-26

Abstract: The publication of the Women's Health Initiative Study in 2002 and the Million Women Study in 2003 on the association of menopausal hormone therapy (HT) and breast cancer were followed by a decrease in the prescription of HT to menopausal women in western countries. In the following years several papers from different countries reported declines in breast cancer incidence and discuss whether this decline is related to the decreased use of menopausal hormone therapy. We contribute further data by analysing breast cancer incidence rates from the Hamburg Cancer Registry, Germany, for the time period 1991–2006 and HT use data from a large case–control study conducted in the Hamburg region. At first we determined whether there is a decline in breast cancer incidence in 2002/2003. To find supporting evidence for a causal relationship between breast cancer incidence and use of menopausal hormones we addressed the following issues: The decline in incidence should be more pronounced in the age groups, in which HT is used predominantly, i.e. age group 50–69. The decline in incidence should be most pronounced for breast cancer types more strongly associated with HT, i.e. invasive lobular cancer. We observed a statistical significant decline in incidence of all invasive breast cancer in 2002/2003 in Hamburg. The increase in breast cancer incidence as well as the decline was most pronounced in the age group 50–69. Regarding the histological types of tumours in this age group the decline was only pronounced for invasive lobular cancer. The estimated prevalence of HT indicates a decreasing hormone use starting in 2001/2002. We found a strong decrease in prescriptions for menopausal hormone therapy between 2002 and 2005. In summary, our data add to the evidence of a relation between breast cancer incidence and menopausal hormone use.

Maternal body mass index and risk of testicular cancer in male offspring: A systematic review and meta-analysis - Uncorrected Proof

Shama Alam, Marie Cantwell, Chris Cardwell, Michael Cook, Liam Murray — 2010-07-23

Abstract: Objectives: To date a number of studies have examined the association between maternal weight and testicular cancer risk although results have been largely inconsistent. This systematic review and meta-analysis investigated the nature of this association. Methods: Search strategies were conducted in Ovid Medline (1950–2009), Embase (1980–2009), Web of Science (1970–2009), and CINAHL (1937–2009) using keywords for maternal weight (BMI) and testicular cancer. Results: The literature search produced 1689 hits from which 63 papers were extracted. Only 7 studies met the pre-defined criteria. Random effects meta-analyses were conducted. The combined unadjusted OR (95% CI) of testicular cancer in the highest reported category of maternal BMI compared with the moderate maternal BMI was 0.82 (0.65–1.02). The Cochran's Q P value was 0.82 and the corresponding I2 was 0%, both indicating very little variability among studies. The combined unadjusted OR (95% CI) for testicular cancer risk in the lowest reported category of maternal BMI compared to a moderate maternal BMI category was 0.88 (0.65–1.20). The Cochran's Q P value was 0.05 and the corresponding I2 was 54%, indicating evidence of statistical heterogeneity. The combined unadjusted OR (95% CI) of testicular cancer risk per unit increase in maternal BMI was 1.01 (0.97–1.06). The Cochran's Q test had a P value of 0.05 and the corresponding I2 was 55% indicating evidence of statistical heterogeneity. Conclusion: This meta-analysis, which included a small number of studies, showed that a higher maternal weight does not increase the risk of testicular cancer in male offspring. Though an inverse association between high maternal BMI and testicular cancer risk was detected, it was not statistically significant. Further primary studies with adjustment for appropriate confounders are required.

Cancer related factors do not explain the quality of life scores for childhood cancer survivors analysed with two different generic HRQL instruments - Uncorrected Proof

2010-07-22

Abstract: The aims: The aims of this Finnish total cohort survey were to compare the health related quality of life (HRQL) of childhood cancer survivors with for age, gender and place of residence matched controls, to analyse whether the disease-related factors do explain the survivors scores, and to evaluate the similarity of HRQL scores gained with two different generic instruments. Methods: Questionnaires (SF-36 version 2 and the 15D) were mailed to 468 survivors and their controls. Results: A total of 271 survivors and 329 controls replied. The survivors rated with both instruments their HRQL in most areas as high or higher than their controls. Mobility score was, however, significantly lower for survivors than controls. Females rated their HRQL lower than respective males. Self-rated happiness had the highest effect in explaining the variation of 15D and mental component summary (MCS) scores. Survivors treated for osteosarcoma or with stem cell transplantation (SCT) rated their physical HRQL significantly lower than the others. SCT treatment indicated significantly lower MCS scores than the reference treatment. Correlation between the physical component summary (PCS) scores and 15D total scores was low (R=0.20–0.28). MCS and 15D total scores correlated (R=0.48–0.60) better with each other, but the gained correlation coefficients still differed significantly from each other (p=0.04) and showed better correlation in the controls. Conclusions: Our findings suggest, that the diagnosis of osteosarcoma, and SCT treatment are substantial risks for adverse HRQL. However, disease related factors did not remarkably explain the variation of HRQL scores gained with generic HRQL instruments. Our findings suggest, that the diagnosis of osteosarcoma, and SCT treatment are substantial risks for adverse HRQL. More evaluation is needed in order to decide whether any of the available generic instruments are feasible for studying HRQL for this special population.

Genetic polymorphisms of glutathione S-transferase genes and susceptibility to colorectal cancer: A case–control study in an Indian population - Uncorrected Proof

2010-07-21

Abstract: Background: Susceptibility to sporadic colorectal cancer is multifactorial and arises from interactive combinations of allelic variants in low-penetrance genes and relevant environmental risk factors. Genetic polymorphisms in metabolic enzymes as gene susceptibility factors may modify colorectal cancer risk. We evaluated the risk of colorectal cancer associated with respective or combined glutathione S-transferase (GST) polymorphisms and assessed the interactions between genes and environmental factors in a case–control study in an Indian population. Methods: The study included 59 colon and 243 rectal cancer cases, and 291 cancer-free healthy controls. GST genotypes were detected by multiplex PCR-based and PCR-RFLP methods. The risk of cancer associated with GST polymorphisms was estimated by calculation of odds ratios (ORs) and confidence intervals (95% CIs) using unconditional logistic regression. Results: The GSTM1 null genotype was found to be associated with a significantly increased rectal cancer risk (OR=1.55; 95% CI, 1.05–2.30), while the GSTT1 null genotype with a greater risk of colon cancer (OR=2.15; 95% CI, 1.04–4.32). A substantial increase of both colon (OR=10.81; 95% CI, 1.11–107.22) and rectal (OR=4.80; 95% CI, 0.94–35.91) cancer risk was shown for the combination of GSTM1 null, GSTT1 null and GSTP1 105Val allele. The combined GSTM1 null and GSTP1 114Val allele also revealed an increased risk for either colon cancer (OR=4.69; 95% CI, 0.84–23.87) or rectal cancer (OR=5.68; 95% CI, 1.79–22.16). Furthermore, the combination of GSTM1 null, GSTT1 null and GSTP1 114Val allele was found in 2 rectal cancer cases. Conclusion: Our results suggest that co-exist of GSTM1 null, GSTT1 null and the variant GSTP1 105Val or 114Val allele may be predisposing risk factors for colorectal cancer in Indian population.

Determinants of adequate follow-up of an abnormal Papanicolaou result among Jamaican women in Portland, Jamaica - Uncorrected Proof

Su Jin Jeong, Ekta Saroha, Jeremy Knight, Michele Roofe, Pauline E. Jolly — 2010-07-21

Abstract: Background: Among Jamaican women, cervical cancer is the second leading cause of cancer mortality but factors that facilitate follow-up of women receiving abnormal Pap smear results are not known. We examined whether socio-demographic factors, factors reported by the women, and assistance received for follow-up facilitate adequate follow-up of abnormal Pap smears. Methods: One hundred and twenty-one women who had abnormal Pap results during June 1998–September 2005 in Portland, Jamaica were interviewed to identify determinants of adequate follow-up. Chi-square, t-test and multivariable logistic regression analysis were used to identify determinants. Results: Only half of the women in this sample sought adequate follow-up. These women had a lower number of surviving children, higher monthly income, and perceived the cost of services to be inexpensive. Advice about the timing of the follow-up activity and the next step to take by the healthcare workers were significant determinants of adequate follow-up. Women who received advice on the timing of follow-up were almost six times (adjusted OR: 5.99, 95% CI: 1.17, 30.66, p<0.05) more likely to seek adequate follow-up after adjusting for other factors. Conclusions: Perceived low cost of services as well as assistance provided by healthcare workers regarding follow-up action helps to facilitate adequate follow-up of abnormal Pap smear results.

Primary exploration of CDR3 spectratyping and molecular features of TCR β chain in the peripheral blood and tissue of patients with colorectal carcinoma - Uncorrected Proof

2010-07-20

Abstract: Background: The immunoscope spectratyping to TRBV CDR3 had been applied in infectious diseases, tumors, autoimmune diseases and so on, this study aimed to primarily explore CDR3 spectratyping and molecular features of TCR β chain in the peripheral blood and tissue of patients with colorectal carcinoma. Methods: Blood and tissue samples were collected from seven patients with colorectal carcinoma (CRC), while blood samples were also collected from two healthy controls as control. Using the real-time fluorescence quantitative reverse transcription polymerase chain reaction (RQ-PCR) and DNA melting curve analysis techniques, the features of T-cell receptor beta chain variable region (TRBV) were determined. Results: The gene melting spectral pattern (GMSP) of 24 TRBV gene families exhibited a highly diverse multimodal shape for most of the TRBV gene families, compared to healthy controls, the more GMSP of patients with CRC showed either a single peak, or several prominent melting peaks (skewed) for certain TRBV gene families. Different patients have different skewed patterns. In the analysis results of sequence, some TRBV CDR3 gene families showed sharing the same motif, such as, TRBV6 of P5, TRBV13.1 of P6 and TRBV21 of P7 (tissue sample) shared the same motif ‘GT’; TRBV1 of P1 and TRBV21 of P7 shared the same motif ‘AGG’, TRBV11 of P1, TRBV21 of P5 and TRBV21 of P7 (tissue sample) shared the same motif ‘TDTQY’, and even TRBV21 of P5 and P7 (tissue sample) shared the large motif ‘SGTDTQY’. As a whole, most of TRBV gene families have the similar motifs ‘X-Q’, the nucleotide ‘X’ mainly was ‘E’, it also was possible be ‘T’, ‘G’ or ‘K’ in some CDR3 gene families of patients with CRC. Conclusions: There were different GMSPs in different patients with CRC, CDR3 spectratyping and the molecular features of TCR β chain in the peripheral blood and tissue of patients with CRC were not same or similar, this information would provide ideas for individualized therapy to CRC.

A higher prediagnostic insulin level is a prospective risk factor for incident prostate cancer - Uncorrected Proof

J. Hammarsten, J.-E. Damber, R. Peeker, D. Mellström, B. Högstedt — 2010-07-20

Abstract: A higher insulin level has been linked to the risk of prostate cancer promotion. However, several reports claim that there is no association between a higher insulin level and the risk of incident prostate cancer. In the present report, the insulin hypothesis was tested once more prospectively in men with a benign prostatic disorder. Three hundred and eighty-nine consecutive patients referred with lower urinary tract symptoms without clinical prostate cancer were included during 1994–2002. Follow-up was performed in 2006. Data were obtained from the Swedish National Cancer Register and the Regional Cancer Register, Oncological Centre, Göteborg, Sweden. At this follow-up, 44 of the patients included had developed prostate cancer. Men with prostate cancer diagnosis had a higher systolic (P<0.001) and diastolic blood pressure (P<0.000), were more obese as measured by BMI (P=0.010), waist (P=0.007) and hip measurements (P=0.041) than men who did not have prostate cancer diagnosis at follow-up. These men also had a higher uric acid level (P=0.040), and a higher fasting serum insulin level (P=0.023) than men who did not have prostate cancer diagnosis at follow-up. Following exclusion of T1a/b prostate cancer cases, the difference of the fasting serum insulin level between the groups was still significant (P=0.038). Our data support the hypothesis that a higher insulin level is a promoter of prostate cancer. Moreover, our data suggest that the insulin level could be used as a marker of the risk of developing prostate cancer. The present findings also seem to confirm that prostate cancer is a component of the metabolic syndrome. Finally, our data generate the hypothesis that the metabolic syndrome conceals early prostate cancer.

Local cluster of germ cell cancer in a cohort of male automotive workers in Germany not explained by previous or concurrent activities and exposures in farming and forestry - Uncorrected Proof

N. Schmeisser, I. Langner, B. Mester, A. Gottlieb, T. Behrens, W. Ahrens — 2010-07-20

Abstract: Objective: To examine whether exposures or activities in farming, forestry and related occupations explain the excess incidence of germ cell cancer observed among male employees in one of the six car-manufacturing plants that is located in a geographic area where farming is frequent. Methods: A cohort based case–control study was conducted among workers in six car-manufacturing plants located in areas with different industrial structure. The study involved 188 cases of germ cell cancer identified through active retrieval in 38 hospitals and 1000 controls, drawn from administrative accounting files, individually matched by year of birth (±2 years). Information regarding tasks and exposures and potential confounding variables were obtained by face-to-face or telephone interviews. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using a conditional logistic regression model adjusted for cryptorchidism and other potential confounders. Results: In this case–control study 5.3% of cases and 6.3% of controls ever worked in agriculture or livestock farming. No increased risks were observed working in agriculture (OR=0.8 95% CI: 0.4–1.6), livestock farming (OR=0.8 95% CI: 0.4–1.6) or for exposure to pesticides (OR=0.7 95% CI: 0.3–1.7), fertilizers (OR=0.8 95% CI: 0.4–1.8) and disinfectants (OR=1.0 95% CI: 0.3–2.8). There were no statistically significant increases in risk associated with ever exposure to salt based wood protection agents (OR=2.3 95% CI: 0.6–9.1), working with plywood (OR=1.4 95% CI: 0.6–3.2), coated wood (OR=1.4 95% CI: 0.5–3.9) or working in forestry (OR=1.7 95% CI: 0.5–6.4). Lagging of exposures did not alter the results. Conclusions: The observed excess incidence in the cohort of automotive workers can be hardly explained by previous or concurrent work in farming or forestry. Because of the small numbers of subjects ever employed in farming the statistical power in assessing associations between agricultural work and agricultural exposures was limited and does not allow final conclusions about the association of farming related exposures and GCC risk.

Characteristics and survival associated with ovarian cancer diagnosed as first cancer and ovarian cancer diagnosed subsequent to a previous cancer - Uncorrected Proof

Zahava Berkowitz, Sun Hee Rim, Lucy A. Peipins — 2010-07-20

Abstract: Objective: To examine the risk of subsequent primary ovarian cancer among women diagnosed previously with cancer (subsequent cohort) and to compare demographic and tumor characteristics affecting overall survival of these women and women diagnosed with first primary ovarian cancer (index cohort). Methods: We identified the two cohorts of women using the 1973–2005 surveillance, epidemiology, and end result data. We calculated relative risk of subsequent primary ovarian cancer and estimated 5-year risks of dying (hazard-ratios) after diagnosis of the first or subsequent primary ovarian cancer in the two cohorts, respectively using Cox modeling. Results: Women diagnosed with index cancers of the corpus uteri, colon, cervix, and melanoma at age younger than 50 had increased risk of ovarian cancer within 5 years after diagnosis (p<0.05); young breast cancer survivors had continued risk beyond 20 years. In 5-year follow-up survival analysis, the factors associated with a better survival (p<0.05) were similar in both cohorts and included more recent diagnosis; localized or regional disease; age <50 years at diagnosis; and being white versus black. A lower risk of dying from mucinous, endometrioid, or non-epithelial tumors than from serous was seen after 15 months (p<0.01), or after 32 months from diagnosis of the index and subsequent cohorts, respectively. Conclusions: Age, stage, and histology affect ovarian cancer survival. The increased risk of ovarian cancer over time, especially among breast and colon cancer survivors who are less than 50 years of age, suggests common etiologies and necessitates careful surveillance by health care providers and increased survivors awareness through educational efforts.

Incidence of cancer in kidney-transplant recipients: A long-term cohort study in a single center - Uncorrected Proof

2010-07-20

Abstract: In a long-term cohort study, we calculated cancer incidences and survival rates after the development of these cancers in kidney-transplant recipients. The cancer incidences were compared with those in the general population. The occurrence of cancer was recorded in all patients who received kidney transplantation between 1966 and 2006. The median follow-up time was more than 9 years with a maximum of almost 40 years. Altogether 327 (17%) of 1906 patients developed cancer after transplantation: 142 (7%) had non-cutaneous malignancies; 178 (9%) cutaneous squamous-cell carcinomas and 138 (7%) basal-cell carcinomas. The cumulative incidence of any cancer was 13%, 33% and 47% after 10, 20 and 30 years, respectively. The incidences of cancers of the oral cavity, stomach, female genital organs, kidney, thyroid gland, leukemias and lymphomas, and cutaneous squamous-cell carcinoma were significantly increased with a highest standardized morbidity ratio of 40 for cutaneous squamous-cell carcinomas. Survival rates after non-cutaneous malignancies were 57%, 43% and 36% and after non-melanocytic skin cancer 99%, 90% and 77% after 1, 3 and 5 years, respectively. The increased incidence of non-cutaneous malignancies after kidney transplantation is associated with a high mortality. Prevention of cancer after kidney transplantation should be a major focus of future research.

Childhood cancer survival: A report from the United Kingdom Childhood Cancer Study - Uncorrected Proof

W. Thomas Johnston, Tracy J. Lightfoot, Jill Simpson, Eve Roman — 2010-07-20

Abstract: Background: Improvements in diagnostic approaches and refinements to treatment protocols have resulted in 5-year survival levels above 70% for children diagnosed with cancer in economically developed parts of the world. For some cancers, including leukaemia and tumours of the central nervous system, age and sex have been identified as important prognostic indicators. Methods: We examined long-term survival, and affects of age and sex, in a population-based case–control study. Children (0–14 years) newly diagnosed with cancer were ascertained between 1991 and 1996 (n=4433). Follow-up information was obtained from the National Health Service (NHS) Information Centre for Health and Social Care which records all exits from the NHS including deaths. Results: For all cancer diagnoses combined, 5-year survival was 72.7% dropping to 67.9% at 15 years. As expected, survival differed between diagnostic subtypes ranging from 38.1% for intracranial embryonal tumours to 96.2% for Hodgkin lymphoma. Compared to girls, boys diagnosed with acute lymphoblastic leukaemia were at a higher risk of dying (RR=1.26, 95% CI 1.03–1.53), whereas boys diagnosed with an intracranial embryonal tumour were at a lower risk of death (RR=0.63, 95% CI 0.43–0.91). Conclusion: Our initial findings are consistent with previous reports, and highlight the importance of considering differences by age and sex. The completeness and population-based nature of the original case–control study is an important feature which will provide the basis for future more detailed investigations linking disease determinants to outcome.

Trends in mortality and mean age at death from lung cancer in Austria (1975–2007) - Uncorrected Proof

Livia Borsoi, Ursula Kunze, Michael Kunze, Ernest Groman, Michael Kundi — 2010-07-14

Abstract: Objective: To investigate trends in mortality and mean age at death from lung cancer (MADLC) compared to mean age at death from all causes (MAD) over the period 1975 - 2007 in Austria. Results are assessed with respect to secular trends in smoking habits. Methods: MAD and MADLC were computed by year and gender as the expected value of a fitted Weibull distribution. Age-period-cohort effects on lung cancer death rates were estimated by hierarchical Poisson models. Results: In females MADLC was on average about 2 years higher than in males and tended to decrease since the mid 1980s, while after the mid 1990s MADLC in males increased such that the difference between men and women shrank to about half a year in 2007. Females dying from lung cancer lost about 6 years of life during the late 1970s but more than 10 years after 2000, while males lost 2 years in the 1970s and 5 years after 2000. Males demonstrated a decreasing risk with increasing year of birth, with the exception of cohorts born during or immediately after the World Wars that showed peak relative risks (RR). Females did not show pronounced birth cohort effect except for a peak RR for cohorts born during and after World War II. Conclusions: MADLC provides additional information about secular trends in addition to incidence data. The declining trend of MADLC in females and in males up to the mid 1990s points to a change of smoking habits with an earlier onset of smoking in both genders. The subsequent increase in males during the last decade may be attributed to an increasing proportion of quitters because smoking cessation delays onset of lung cancer.

Cancer screening behaviors among smokers and non-smokers - Uncorrected Proof

2010-07-09

Abstract: Objective: We explored whether smoking is associated with cancer screening behaviors. Methods: We used data from the 2007 Florida Behavioral Risk Factor Surveillance System and the Florida Tobacco Callback Survey to examine screening behaviors related to four cancer types (breast, cervical, prostate, and colorectal). Using multiple logistic regression analyses, we examined the association between smoking status and health screening behaviors. Results: For 10 of the 11 cancer screening variables, being a current smoker was significantly associated with being less likely to ever have been screened and also less likely to be compliant with screening guidelines. For breast and cervical cancer, level of nicotine dependence was also significantly related to compliance with screening recommendations; women with higher levels of dependence were less likely to be compliant. Conclusions: Our results support the notion that individuals’ actions related to their health are consistent across different types of behaviors. We found that smokers were less likely to engage in cancer screening behaviors. In addition, among smokers, individuals with greater nicotine dependence had lower compliance with some screening tests. Physicians should ensure that their patients who smoke are receiving appropriate and adequate screening for cancer.

Measuring the effect of including multiple cancers in survival analyses using data from the Canadian Cancer Registry - Uncorrected Proof

Larry F. Ellison — 2010-07-07

Abstract: Background: In survival analyses using cancer registry data, second and subsequent primary cancers diagnosed in individuals are typically excluded. However, this approach may lead to biased comparisons of survival between cancer registries, or over time within a single registry. Purpose: To examine the impact of including multiple primary cancers in the derivation of survival estimates using data from a population-based national cancer registry. Methods: Five-year relative survival estimates for persons aged 15–99 years at diagnosis were derived using all eligible primary cases from the Canadian Cancer Registry (CCR)—a population-based registry containing information on cases diagnosed from 1992 onward—and then again using first primary cases only. Any pre-1992 cancer history of persons on the CCR was obtained by using auxiliary information. Results: The inclusion of multiple cancers resulted in lower estimates of 5-year relative survival for virtually all cancers studied. The effect was somewhat attenuated by age-standardization (e.g., from 1.3% to 1.0% for all cancers combined), and was greatest for bladder cancer (−2.4%) followed by oral cancer (−1.9%)—cancers that had the first and third lowest proportions of first cancers, respectively. For the majority of cancers the difference was less than 1.0%. Cancers for which there was virtually no difference (e.g., lung, pancreatic, ovarian and liver) tended to be those with a poor prognosis. Conclusion: Inclusion of second and subsequent primary cancers in the analysis tended to lower estimates of relative survival, the extent of which varied by cancer and age and depended in part on the proportion of first primary cancers.

Evaluation of cancer surveillance completeness among the Italian army personnel, by capture–recapture methodology - Uncorrected Proof

2010-07-07

Abstract: Objective: This study provides an assessment of completeness of cancer surveillance and incidence estimates for all malignancies, Hodgkin's lymphoma and thyroid cancer in the Italian army, for the years 2001–2007. Methods: The two-source capture–recapture method was employed, using both Chapman's and Chao's formulae, on the basis of cancer notifications from military hospitals and unit infirmaries. The estimated incident cases were then confronted with the corresponding expected cases; the standardized incidence ratios and 95% confidence intervals (SIR [95% CI]) were then calculated. Results: A total of 442 cancer notifications, concerning 371 cases, were reported (311 from army hospitals and 131 from unit infirmaries; of these, 71 were overlapping). The estimated total number of cases, by Chapman's and Chao's formulae, was 571 and 688, respectively. Overall, sensitivity of the surveillance system was 65% by Chapman's and 54% by Chao's estimators. Completeness of notification was significantly higher in younger patients, in those previously deployed in Bosnia or Kosovo, and for cases of Hodgkin's lymphoma. Estimated SIRs, using both formulae, were not significant for all malignancies and Hodgkin's lymphoma, but significant for thyroid cancer (SIR: 2.25 [1.61–2.89] by Chapman's formula, and 3.12 [1.81–4.43] by Chao's estimator). Conclusion: Completeness of cancer registry of the Italian military is low, and methods to improve its sensitivity are discussed. Overall, the estimated number of incident cancer cases, including Hodgkin's lymphoma, is not significantly higher than expected, except thyroid cancer. The increased incidence of this malignancy requires further investigation; however, in the military, as well as in the general population, this may be partly due to the growing availability of diagnostic opportunities in the last decades. Moreover, detection of thyroid cancer may be further facilitated by a selection bias generated by the annual and pre-/post-deployment medical examinations and blood tests routinely performed on all military personnel.

Risk factors associated with the occurrence of breast cancer after bilateral salpingo-oophorectomy in high-risk women - Uncorrected Proof

2010-07-05

Abstract: Introduction: Bilateral salpingo-oophorectomy (BSO) is a common procedure for preventing breast and ovarian cancer in high-risk women. The goal of this study was to determine the incidence of subsequent breast cancer (BC) in a high-risk population and to identify clinical and epidemiological predictors of BC following BSO. Materials and methods: One hundred and thirty-three consecutive high-risk women, tested for BRCA1 and BRCA2 mutations due to family history, underwent preventive or therapeutic BSO at one of the study hospitals. One hundred and three patients had breast tissue at risk and were considered evaluable for the event-free survival analysis. Twenty-five women harbored a deleterious mutation in BRCA1 and 25 in BRCA2 genes. Results: Fifteen cases of invasive BC were diagnosed with a median interval of 49 months after BSO. Multivariate analysis showed that a prior BC after 50 years of age (p=0.004), age over 50 years at the time of BSO (p=0.005), and prior replacement or contraceptive hormonal treatment (p=0.007) were significantly associated with a shorter event-free survival. Conclusion: In conclusion, age at prior diagnosis of cancer, age at BSO and prior hormonal treatment may be predictors of breast cancer after BSO.

CHEK2 gene alterations in the forkhead-associated domain, 1100delC and del5395 do not modify the risk of sporadic pancreatic cancer - Uncorrected Proof

2010-07-05

Abstract: Checkpoint kinase 2 gene (CHEK2) alterations increase risk of several cancer types. We analyzed selected CHEK2 alterations in 270 Czech pancreatic cancer patients and in 683 healthy controls. The pancreatic cancer risk was higher in individuals who inherited rare alterations in CHEK2 region involving forkhead-associated domain other than I157T (OR=5.14; 95% CI=0.94–28.23) but the observed association was non-significant (p=0.057). The most frequent I157T mutation did not alter the pancreatic cancer risk and neither the followed deletion of 5395bp nor c.1100delC were found in any of pancreatic cases. We conclude that the I157T, other alterations in its proximity, del5395 and c.1100delC in CHEK2 do not predispose to pancreatic cancer risk in the Czech population.

Socioeconomic status and non-melanoma skin cancer: A nationwide cohort study of incidence and survival in Denmark - Uncorrected Proof

2010-07-05

Abstract: Background: The two main types of non-melanoma skin cancer differ with the pattern of exposure to ultraviolet radiation (UVR): basal cell carcinoma (BCC) appears to be more closely related to intermittent solar exposure and sunburn, while the risk for squamous cell carcinoma (SCC) is a result of lifetime cumulated exposure to UVR. As these exposures may differ by social position, we investigated its role in the risk for and survival after BCC and SCC diagnosed in Denmark in 1994–2006 with follow-up through 2006. Methods: The analyses were based on 52,166 cases of BCC and 5033 cases of SCC in a cohort of 3.7 million people born between 1925 and 1976 and residing in Denmark in 1992–2006. Information on cancer cases and socioeconomic indicators were obtained from population-based registries. We used log-linear Poisson regression models to estimate incidence rate ratios and cumulative relative survival to estimate survival up to 10 years after the first incident cases of BCC and SCC. Results: High socioeconomic status, measured by both education and disposable income, was strongly associated with a higher risk for BCC, whereas there was no association between SCC and educational level and only a weak association with income. In general, relative survival after BCC was better than after SCC; the pattern of survival was not affected by socioeconomic indicators. Conclusions: The observed pattern of social status and risk for non-melanoma skin cancer differed substantially for the two cancer types, supporting the hypothesis that they may have different aetiologies.

Nrf2–ARE signaling pathway and natural products for cancer chemoprevention - Uncorrected Proof

Cui Rong Zhao, Zu Hua Gao, Xian Jun Qu — 2010-07-05

Abstract: One of the potential strategies for preventing cancers is using food-based natural products to induce cytoprotective enzymes including phase II and antioxidative enzymes that act in concert to detoxify and eliminate harmful reactive intermediates formed from carcinogens. The antioxidant response element (ARE), which is activated upon binding of the nuclear factor E2-related protein 2 (Nrf2) transcription factor protein, has been identified in the regulatory regions of numerous genes encoding cytoprotective enzymes. Under basal condition, Nrf2 is at low level, sequestered in the cytoplasm by being tethered to an actin binding Kelch-like ECH associating protein 1 (Keap1). Pharmacological and putative chemopreventive agents trigger the release of Nrf2 from Keap1, allowing it to translocate into the nucleus and drive the gene expression of detoxifying enzymes to perform cancer chemoproventive effect. Via reviewing Pubmed, we summarized the current progress in the molecular mechanisms of Nrf2 regulation as well as highlighted the Nrf2/ARE activators from natural products, which will potentially be used as chemopreventive agents for cancer patients.

Distribution of TYMS, MTHFR, p53 and MDR1 gene polymorphisms in patients with breast cancer treated with neoadjuvant chemotherapy - Uncorrected Proof

2010-07-05

Abstract: Purpose To investigate the role of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms in breast cancer patients treated with 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy. Results Observed allelic frequencies were: TSER, (2) 0.54 and (3) 0.46; MTHFR C677T, (C) 0.59 and (T) 0.41; p53 Arg72Pro, (Arg) 0.73 and (Pro) 0.27; MDR1 C3435T, (C) 0.52 and (T) 0.48. MTHFR allele T and p53 allele Pro were strongly associated with toxicity due to chemotherapy (odds ratio, 7.1 (95% confidence interval, 1.4–36.1; p=0.018) and 7.0 (95% confidence interval, 1.2–40.5; p=0.029), respectively). Conclusion We introduced new data related to the contribution of p53 codon 72 to toxicity due to 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy in patients with breast cancer.

The c.469+46_56del mutation in the homeobox MSX1 gene—A novel risk factor in breast cancer? - Uncorrected Proof

2010-06-28

Abstract: Purpose: The aim of this study was to investigate the association of a 11 nucleotide deletion, the c.469+46_56del mutation, in the intron of the homeobox MSX1 gene and breast cancer occurrence and characteristics. Methods: The mutation was genotyped in peripheral blood lymphocytes of 200 breast cancer patients and 203 controls by single-strand conformational PCR and DNA sequencing. Results: The del/del variant of the c.469+46_56del mutation increased the risk of breast cancer occurrence (OR 2.20; 95% CI 1.41–3.44, p<0.05). We did not observe any association between genotypes of this mutation and lymph node status, Bloom–Richardson grading, estrogen and progesterone receptors and HER2 expression. Conclusions: The del/del genotype of the c.469+46_56del mutation in the MSX1 gene may be associated with the increased risk of breast cancer in Polish population and may be considered as an early marker in this disease.

Combined effects of serum trace metals and polymorphisms of CYP1A1 or GSTM1 on non-small cell lung cancer: A hospital based case–control study in China - Uncorrected Proof

2010-06-28

Abstract: Introduction: The limited information for effects of serum trace elements and genetic polymorphisms on lung cancer is available. Based on a hospital based case–control study, the epidemiological questionnaires were completed by face to face interview, and the gene polymorphisms were tested by RFLP–PCR, and serum trace metals were measured by atomic absorption spectrophotometer, and the data was analyzed by the logistic regressive models. Results: The high serum copper level (>1500ng/ml) or serum copper/zinc ratio (>1) was the risk factors of NSCLC (OR=3.10, 11.03, respectively), but the ORs of the higher serum Zn (>1200ng/ml), Se (>50ng/ml) or Cr3+ (>600ng/ml) for NSCLC were all significantly less than 0.20 (all p<0.01) indicating strong protection against NSCLC. While the OR of CYP 1A1 variants carriers with a higher serum Cu or Cu/Zn ratio level was around 3.38 and 12.59, respectively, the risk of CYP1A1 variants carriers with a higher serum Zn is 0.18, Se 0.04 or Cr3+ 0.28. Similarly, compared with the carriers of GSTM1 power with a lower serum Zn, Se or Cr3+, the OR of the carriers of GSTM1 null with a higher serum Zn, Se and Cr3+ was separately 0.16, 0.07 and 0.26, highlighting the protection against NSCLC. Conclusions: Our findings suggested that CYP1A1 or GSTM1 variants may significantly modify the associations between level of serum trace metals (Cu, Zn, Se or Cr) and NSCLC, indicating the intriguing pathogenesis of lung cancer.

Intake of fruits and vegetables, and risk of endometrial cancer in the National Institutes of Health-American Association of Retired Persons Diet and Health Study - Uncorrected Proof

2010-06-28

Abstract: Background: Fruits and vegetables contain a wide variety of phytochemicals which may have anti-carcinogenic effects. Although the results of case–control studies have suggested a possible protective effect of fruit and vegetable intake on the risk of endometrial carcinoma, few cohort studies have examined this association. Materials and methods: We used data from the NIH-AARP Diet and Health Study to assess the association of fruit and vegetable consumption, as well as intake of specific botanical groupings of fruits and vegetables, with endometrial cancer risk among 112,088 women who completed a food-frequency questionnaire at baseline, in 1995–1996. During 8 years of follow-up 1142 incident cases of endometrial cancer were ascertained. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Results: After adjustment for covariates, HRs for the highest compared to the lowest quintile of total fruit and total vegetable intake were 1.30 (95% CI 1.04–1.61, P for trend 0.05) and 1.09 (95% CI 0.90–1.33, P for trend 0.55), respectively. No inverse associations were observed for intake of any of 13 botanical groupings of fruits and vegetables. Conclusions: Results from this large prospective study do not support a protective role of a high intake of fruits or vegetables on the risk of endometrial cancer in older women.

Health-related quality of life outcomes among cervical cancer survivors: Examining ethnic and linguistic differences - Uncorrected Proof

Kimlin T. Ashing-Giwa, Jung-Won Lim — 2010-06-28

Abstract: Background: This study aims to investigate the utility of an explanatory health-related quality of life (HRQOL) model for cervical cancer survivors. Specifically, this study focuses on the different patterns in the structural model of HRQOL by ethnic and language groups. Methods: Secondary data derived from 560 European- and Latina-American cervical cancer survivors was used. The study methodology was guided by the Contextual Model of health-related quality of life. Results: Structural equation modeling demonstrated significant differences in the overall structural models for HRQOL by ethnicity. For example, European-Americans showed significant association between radiation therapy and HRQOL, while life burden was related to sexual impact for Latina-Americans only. The results showed the significant mediating effects of general health status and psychological well-being between patient–doctor relationship and HRQOL, and between life burden and HRQOL, respectively, for all ethnic and language groups. While language group differences (limited English vs. English proficient) among Latina-Americans emerged in bivariate analyses; these distinctions were not upheld in the overall structural models. Conclusion: The unique contribution of the individual- and systemic-level components in predicting overall HRQOL outcome seems to vary by ethnic group membership. Our findings advance our understanding of the predictors and the association among the predictors of HRQOL. This study may contribute to the evolution of culturally and linguistically responsive HRQOL conceptual frameworks and instrumentation for vulnerable populations.

Diabetes, physical activity and breast cancer among Hispanic women - Uncorrected Proof

2010-06-18

Abstract: Purpose: We assessed the association between diabetes and breast cancer and whether physical activity modified the effect of diabetes on breast cancer in Hispanic women. Methods: We used data from a case-control study of breast cancer among Hispanic women aged 30–79 conducted between 2003 and 2008 on the Texas–Mexico border. In-person interviews were completed with 190 incident breast cancer cases ascertained through surgeons and oncologists, and 979 controls who were designated as both high-risk (n=511) and low-risk (N=468) for breast cancer (with respective response rates of 97%, 83% and 74%). Results: After adjustment for menopausal status and mammography screening, there was no effect of diabetes on breast cancer risk (high-risk control group odds ratio [OR] 1.02, 95% confidence interval [CI] 0.71–1.48; low-risk control group OR 0.87, 0.58–1.30). Women who had a diabetes history and did not exercise were at no risk of breast cancer (OR 0.96, 95% CI 0.63–1.48) or a slightly reduced breast cancer risk (low-risk control group OR 0.72, 95% CI 0.46–1.15) depending on the control group used, while women with diabetes who did exercise had significantly reduced breast cancer risk (OR 0.41, 95% CI 0.21–0.83) regardless of the control group used (high-risk control group p-value for interaction=0.013, low-risk control group p-value for interaction 0.183). Conclusions: Should other studies confirm our results, physical activity should be explored as a means of reducing breast cancer risk in diabetic women.

Polymorphisms of glutathione-S-transferase M1 and T1 and prostate cancer risk in a Tunisian population - Uncorrected Proof

Yousra Souiden, Manel Mahdouani, Kamel Chaieb, Rafick Elkamel, Kacem Mahdouani — 2010-06-17

Abstract: Several genes involved in the metabolism of carcinogenesis have been found to be polymorphic in the human population, and specific alleles are associated with increase risk of cancer of various sites. This study is focused on the polymorphic enzymes glutathione-S-transferase M1 (GSTM1) and T1 (GSTT1) that involved in the detoxification of many xenobiotics involved in the etiology of prostate cancer. Objective. To evaluate whether GSTM1 and/or GSTT1 contribute to prostate cancer (CaP) etiology, we studied 110 incident CaP cases and 122 controls. Results. The probability of having CaP was increased in men who had homozygous deleted (non-functional) genotypes at GSTT1 (OR=2.17; 95% CI=1–3.79) but not GSTM1 (OR=0.89; 95% CI=0.66–1.88). Hence, individuals lacking the GSTT1 gene are at approximately twofold higher risk of developing prostate cancer in comparison with individuals with at least one active allele in the GSTT1 locus. Conclusion. These results suggest that GSTT1 is associated with CaP risk. The effect of smoking associated with the GSTT10/0 genotype was not found to affect the risk of prostate cancer.

Hospitalization for osteoarthritis and prostate cancer specific mortality among Swedish men with prostate cancer - Uncorrected Proof

2010-06-10

Abstract: Purpose: To examine the potential role of nonsteroidal anti-inflammatory drugs (NSAIDs) use on prostate cancer (PCa) specific mortality after diagnosis. Methods: We studied the association between hospitalization for osteoarthritis prior to PCa diagnosis, as a surrogate for heavy use of NSAIDs, and PCa specific mortality in a large population of PCa patients in Sweden in 1980–2004. Results: Hospitalization for osteoarthritis before PCa diagnosis was associated to a lower PCa specific mortality (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.88–0.96), but not to the risk of death from other causes (HR, 1.03; 95% CI, 0.99–1.08). The association was stronger among younger patients and patients diagnosed in earlier calendar years. Conclusions: Our data demonstrate a modestly decreased PCa specific mortality among PCa patients with hospitalization for osteoarthritis prior to PCa diagnosis, compared to those without such experience. This finding lends support to the hypothesis that NSAIDs use may influence PCa progression.

Occupational exposure to gasoline and the risk of non-Hodgkin lymphoma: A review and meta-analysis of the literature - Uncorrected Proof

Eleanor V. Kane, Rob Newton — 2010-06-09

Abstract: Gasoline comprises over 500 chemicals, including the known or suspected carcinogens benzene, 1,3-butadiene, ethylbenzene and methyl tert-butyl ether (MTBE). To assess whether work in the production, distribution and use of gasoline is associated with non-Hodgkin lymphoma (NHL), we reviewed the published literature on this topic. English-language peer-reviewed articles were identified by keyword searches of bibliographic databases. Twenty-two cohorts and thirteen case–control studies examined the risk of NHL among persons employed in the downstream petroleum industry. No positive associations were found with the exception of one study. The pooled risk estimate from a random-effects meta-analysis was 1.02 (95% confidence interval (CI) 0.94–1.12). Although there were no estimates available, exposure is likely to have varied by occupation, location and time period; there was no evidence however that risk estimates varied by any of these factors. NHL is a heterogeneous disease, yet no data were reported for NHL subtypes. In conclusion, there is no suggestion across an extensive literature that exposure to gasoline at the levels workers’ experience in an occupational setting increases the risk of NHL.

Knowledge, perception and practices of colorectal cancer screening in an ethnically diverse population - Uncorrected Proof

2010-06-09

Abstract: Background: Colorectal cancer (CRC) screening improves survival and its success depends on the participation of the at-risk population. Few studies have adequately assessed screening knowledge, perception and participation according to birthplace. This study assesses the knowledge and perception of CRC in an ethnically diverse population, and evaluates the association with screening participation and intention. Identification of specific predictors of screening may aid the development of interventions to improve overall CRC screening. Methods: An interview-based survey, conducted on subjects aged 30–70 years, assessed knowledge and perception towards CRC and screening tests. Primary endpoints were screening participation and intent. Statistical methods used were Chi-square, Mann–Whitney U and logistic regression. Results: A total of 543 subjects (43% males, 53% Australian-born (AB), 63% aged 50 years and above) were recruited. Compared with AB, non-Australian-born (NAB) respondents had poorer knowledge, and NAB background predicted for poorer knowledge independent of sex, education, media and familiarity with CRC patient. Compared with AB respondents aged 50 years and above, NAB respondents had lower screening participation (17.4% vs. 31.8%; P=0.01), lesser intention (75.8% vs. 90.5%; P<0.001), and had received fewer doctors’ screening recommendations (16.5% vs. 27.1%; P=0.04). In multivariate analysis, doctors’ recommendation, media and improved perception independently predicted screening participation; knowledge and media exposure predicted intent. Conclusions: The knowledge of CRC and screening is significantly poorer in the immigrant population. Knowledge predicts for greater screening intent. Therefore, implementing language- and culture-specific educational programs involving medical practitioners and media are necessary to improve CRC screening participation rates.

Do adipokines underlie the association between known risk factors and breast cancer among a cohort of United States women? - Uncorrected Proof

2010-06-09

Abstract: Obesity is a well-established risk factor for postmenopausal breast cancer, but mechanisms underlying the association are unclear. Adipocyte-derived, cytokine-like adipokines have been suggested as contributory factors. To evaluate their association with breast cancer risk factors and breast cancer risk, we conducted a nested case-control study of 234 postmenopausal breast cancer cases and 234 controls in a cohort of U.S. women with prospectively-collected serum samples obtained in the mid 1970s and followed for up to 25 years. Adiponectin, absolute plasminogen activator inhibitor-1 (aPAI-1), and resistin were measured by a multiplex immunoassay. Sex hormones were available for 67 cases and 67 controls. Among controls, we found that lower levels of adiponectin and higher levels of aPAI-1 were correlated with increasing levels of estradiol (Spearman r=−0.26, p-value=0.033; r=0.42, p=0.0003), decreasing levels of sex hormone binding globulin (r=0.38, p=0.0013; r=−0.32, p=0.0076), and increasing body mass index (BMI) (r=−0.31, p=<0.0001; r=0.39, p=<0.0001). Hormones were not associated with resistin. Among the relatively small percentage of women using postmenopausal hormones at the time of blood collection (13.7%), aPAI-1 levels were higher than in non-users (p=0.0054). Breast cancer risk was not associated with circulating levels of adiponectin (age-adjusted p for linear trend=0.43), aPAI-1 (p=0.78), or resistin (p=0.91). The association was not confounded by BMI, parity, age at first full-term birth, age at menopause, current postmenopausal hormone use, and circulating sex steroid hormones. Furthermore, adipokine associations were not modified by BMI (p>0.05). The lack of association with risk may be due to measurement error of the laboratory assays. In conclusion, lower levels of adiponectin and higher levels of aPAI-1 measured in prospectively-collected serum from postmenopausal women were associated with increasing BMI but not breast cancer risk.

Physical activity reduces the risk of breast cancer: A case–control study in Tunisian population - Uncorrected Proof

2010-06-03

Abstract: Purpose: The relation between breast cancer and lifetime history of physical activity was studied to determine whether exercise may reduce this disease development. Methods: The case–control study was conducted on 400 women with histological confirmed breast cancer operated during the 2006–2009 period at Farhat Hached University Hospital, Sousse, Tunisia, and 400 cancer-free controls, aged 25–75 years. The Physical activity was assessed using a structured questionnaire on each activity: type, duration, frequency, and intensity. Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CI) and a full confounding assessment was included in this analysis. Results: These cases had lower lifetime averages for total physical activity for both forms of activity measurements (hours/week/year and MET-hours/week/year) and (Ptrend<0.001 and Ptrend=0.002, respectively). Significant risk reductions were found in total physical activity for both forms of activity measurements (OR=0.27, 95% CI: 0.18–0.52, OR=0.42, 95% CI: 0.26–0.73, respectively) for the highest versus the lowest level of activity (Ptrend=0.001 and 0.004, respectively). The stratification by menopausal status showed a significant 56% reduction in breast cancer risk for post-menopausal women (Ptrend=0.001, adjusted for age). The risk was further reduced to 68% (Ptrend=0.002, multivariate adjusted). Among pre-menopausal women, the total physical activity was not significantly associated with reduced risk, ORs were 0.88 (95% CI: 0.40–1.99, age adjusted) and 0.43 (95% CI: 0.12–1.38, multivariate adjusted). Conclusion: These data are in concordance with the majority of previous reports which involved physical inactivity as an important risk factor for breast cancer.

Smoking related risk involved in individuals carrying genetic variants of CYP1A1 gene in head and neck cancer - Uncorrected Proof

K. Sabitha, M. Vishnuvardhan Reddy, Kaiser Jamil — 2010-05-31

Abstract: Background: CYP1A1 is one of the commonest genes which had been widely investigated to find the risk of various malignancies in different ethnic groups. The polymorphism in these genes with a combination of environmental exposure has been hypothesized to confer a differential risk of cancer for individuals carrying these genetic variants. Based on this model, individuals with higher CYP1A1 activity would be at increased risk of cancer when exposed to high levels of smoke components. The proposed mechanism involves cytochrome P450 1A1 (CYP1A1), a gene that is inducible by xenobiotics to produce genetic susceptibility for malignancies. Patients and procedures: We performed a case–control study in 205 cases with histopathologically confirmed squamous cell carcinoma of head and neck and reported habits of bidi or cigarettes smoking and 245 similar controls to investigate the role of CYP1A1 polymorphisms in the risk of head and neck cancers especially among smokers of Hyderabad Indian population. Venous blood samples (5ml) were collected from patients and control groups; genomic DNA was extracted and used for polymerase chain reaction (PCR) to determine the genotypes. RFLP assays were designed to detect each of the variant CYP1A1 alleles. Results and discussion: CYP1A1m1/m1 genotype (OR=8.12, 95% CI: 3.27–21.30) and CYP1A1w1/m1 showed elevated risk when compared with CYP1A1w1/w1. Similarly CYP1A1w2/m2 (OR=1.58, 95% CI: 0.94–2.67) and CYP1A1m2/m2 (OR=6.31, 95% CI: 2.74–18.69) genotypes also showed elevated risk when compared with CYP1A1w2/w2 genotype. This data demonstrated that smoking was a risk factor for head and neck cancers. The m2 mutations were in close linkage disequilibrium with the m1 mutations; 53% m1 mutants had the mutation in the m2 site. Conclusion: Those individuals carrying at least one CYP1A1 m1 or m2 variant allele were at a 2-fold elevated risk for head and neck cancer. Our data clearly demonstrates that CYP1A1 is an important determinant in susceptibility to tobacco-induced head neck carcinogens and there is an association between genetic polymorphism in the CYP1A1 locus and elevated risk of the type of smoking among Indians. This appears to be a new and important prognostic and diagnostic marker for determining the risk of head and neck cancers genetically.

Detection of gastric carcinoma-associated antigen MG7-Ag in human sera using surface plasmon resonance sensor - Uncorrected Proof

Xiangyi Fang, Jun Tie, Yonghong Xie, Quanjiang Li, Qingchuan Zhao, Daiming Fan — 2010-05-31

Abstract: MG7-Ag is a kind of gastric cancer-specific tumor-associated antigen and has been investigated to serve as a marker of gastric cancer for early diagnosis. Surface plasmon resonance (SPR) sensor was used for the detection of MG7-Ag in the sera of gastric cancer patients to develop an innovative, simple and rapid assay method for early diagnosis. The specific monoclonal MG7 antibodies were used as capture and detection receptors which were immobilized on the surface of SPR sensor chips for MG7-Ag identification in the human sera. The measurements include 9 cases of gastric cancer patients and 2 cases of healthy blood donors and a MKN45 cancer cell lysate solution sample for positive control. The binding of MG7-Ag onto the sensor surface was observed from SPR spectra. The sera of most gastric cancer patients revealed much higher expression level of MG7-Ag than healthy human sera did in SPR measurement. The initial results demonstrate that the SPR biosensor has the potential for its application in the early diagnosis of gastric cancer. However, more tests need to be done to confirm the detection limitation and the criterion for cancer risk evaluation in early diagnosis.

Gastric adenocarcinoma and Helicobacter pylori: Correlation with p53 mutation and p27 immunoexpression - Uncorrected Proof

2010-05-31

Abstract: Introduction: Helicobacter pylori infection is an established risk factor for gastric cancer development, but the exact underlying mechanism still remains obscure. The inactivation of tumor suppressor genes such as p53 and p27KIP1 is a hypothesized mechanism, although there is no consensus regarding the influence of H. pylori cagA(+) in the development of these genetic alterations. Goals: To verify the relationship among H. pylori infection, p53 mutations and p27Kip1 Protein (p27) expression in gastric adenocarcinomas (GA) seventy-four tissues were assayed by PCR for H. pylori and cagA presence. Mutational analysis of p53 gene was performed by single-strand conformation polymorphism (SSCP). Seventy tissues were analyzed by an immunohistochemical method for p27 expression. Results: From the samples examined, 95% (70/74) were H. pylori positive, 63% cagA(+). Altered p53 electrophoretic mobility was found in 72% of cases and significantly more frequent in the presence of cagA. Considerable reduction in p27 expression (19%) was found with a tendency for association between cagA(+) and p27(−), although the results were not statistically significant. Concomitant alterations of both suppressor genes were detected in 60% of cases. In the cases cagA(+), 66.7% of them had these concomitant alterations. Conclusions: The data suggest that H. pylori cagA(+) contributes to p53 alteration and indicate that concomitant gene inactivation, with reduced p27 expression, may be a mechanism in which H. pylori can promote the development and progression of gastric cancer.

DNA methylation in pre-diagnostic serum samples of breast cancer cases: Results of a nested case–control study - Uncorrected Proof

2010-05-31

Abstract: Promoter methylation of tumor suppressor genes is a frequent and early event in breast carcinogenesis. Paired tumor tissue and serum samples from women with breast cancer show that promoter methylation is detectable in both sample types, with good concordance. This suggests the potential for these serum markers to be used for breast cancer detection.The current study was a case–control study nested within the prospective New York University Women's Health Study cohort aimed to assess the ability of promoter methylation in serum to detect pre-clinical disease. Cases were women with blood samples collected within the 6 months preceding breast cancer diagnosis (n=50). Each case was matched to 2 healthy cancer-free controls and 1 cancer-free control with a history of benign breast disease (BBD).Promoter methylation analysis of four cancer-related genes: — RASSF1A, GSTP1, APC and RARβ2, — was conducted using quantitative methylation-specific PCR. Results showed that the frequency of methylation was lower than expected among cases and higher than expected among controls. Methylation was detected in the promoter region of: RASSF1A in 22.0%, 22.9% and 17.2% of cases, BBD controls and healthy controls respectively; GSTP1 in 4%, 10.4% and 7.1% respectively; APC in 2.0%, 4.4% and 4.2% respectively and RARβ2 in 6.7%, 2.3% and 1.1% respectively.Methylation status of the four genes included in this study was unable to distinguish between cases and either control group. This study highlights some methodological issues to be addressed in planning prospective studies to evaluate methylation markers as diagnostic biomarkers.

Gene–gene interactions of drug metabolizing enzymes and transporter protein in the risk of upper aerodigestive tract cancers among Indians - Uncorrected Proof

2010-05-31

Abstract: Introduction: The combined genetic effects of single nucleotide polymorphisms may additively or synergistically contribute to the increased cancer risk. The interactions associated with xenobiotic metabolizing enzymes and transporter protein involved in the biotransformation and transport of xenobiotics could determine the functional outcomes over the independent effects of a single susceptibility gene in the risk of upper aerodigestive tract cancers. Methods: The hospital-based case–control study evaluated CYP1A1 (*2A and *2C), CYP2E1 (*1B, *5B, and *6), GST (M1, T1, and P1) and ABCB1 3435C>T polymorphisms among 408 histopathologically confirmed cases and 220 controls using polymerase chain reaction based methods in an Indian population. Results: The multivariate logistic regression analyses demonstrated potentially high risk gene–gene interactions with the concurrent deletions of the GSTT1 and GSTM1 genes and GSTP1 variant genotypes (OR 5.81; 95% CI 1.01–40.28), the deletions of GSTT1 and GSTM1 genotypes with variant genotypes of CYP1A1*2A (OR 8.21; 95% CI 1.91–49.48), GSTT1 and GSTM1 deficient genotypes along with CYP2E1*1B variant genotypes (OR 6.73; 95% CI 1.32–22.81), the polymorphic genotypes of ABCB1 and deficient GSTT1 (OR 6.08; 95% CI 2.21–16.76) and an enhanced risk with the combined variant genotypes of CYP1A1*2A, GSTT1 and ABCB1 (OR 11.14; 95% CI 2.70–46.02). Conclusion: The findings indicate that the interactions associated with various drug metabolizing enzymes and transporter protein exhibit high risk for UADT cancers than that ascribed to a single susceptible gene. This was particularly established among the polymorphic carriers of CYP1A1*2A, GSTT1 and ABCB1 genes in the population investigated.

Glutathione S-transferase T1 gene deletion polymorphism and lung cancer risk in Chinese population: A meta-analysis - Uncorrected Proof

Yadong Wang, Haiyan Yang, Li Li, Haiyu Wang — 2010-05-31

Abstract: Genetic variations in metabolic genes are considered to modulate metabolic process of carcinogens and are suggested to be related to cancer risk. However, epidemiological results are not always consistent. In this meta-analysis, we evaluated reported studies of association between polymorphism of glutathione S-transferase T1 gene (GSTT1) and the risk of lung cancer in Chinese population. We found an increased lung cancer risk among subjects carrying GSTT1 null genotype [odds ratio (OR)=1.36, 95 percent confidence interval (95% CI): 1.09–1.69], using 1625 cases and 2188 controls from 11 studies. We also observed an increased risk of lung cancer among null genotype carriers in squamous cell carcinoma and andenocarcinoma, and on the basis of population control in stratified analyses. The meta-analysis suggests that GSTT1 deletion polymorphisms may have an effect on the susceptibility of lung cancer in Chinese population, and a study with the larger sample size is needed to further evaluate gene–gene and gene–environment interaction on GSTT1 deletion polymorphisms and lung cancer risk in Chinese population.

Explaining the effects of socio-economic deprivation on survival in a national prospective cohort study of 1909 patients with head and neck cancers - Uncorrected Proof

2010-05-31

Abstract: Background: Socio-economic differences in survival from head and neck cancers are among the largest of any malignancies. Population-based data have been unable to explain these differences. Aims: To describe survival from head and neck cancers in a large cohort of patients for whom a range of socio-economic, demographic, behavioural and casemix data was available. Methods: Prospective cohort study using data from the Scottish Head and Neck Audit on all patients diagnosed with a head and neck cancer in Scotland between 1st September 1999 and 31st August 2001 linked to General Register Office for Scotland death records to 30th June 2006. Cox proportional hazards models were produced to describe adjusted hazards of death according to socio-economic circumstances, using validated area-based DEPCAT scores. Results: Data on 1909 patients were analysed. 71.0% were male and mean age was 64.3 (SD 12.2) years. Overall 5-year survival was 45.6% (95% CI: 43.4–47.8%). In order of strength of association in univariate regression, World Health Organisation Performance Status, disease stage, patient age, tumour site, smoking status, alcohol use, tumour differentiation, and deprivation were significant predictors of all-cause mortality but after multiple adjustment, deprivation was no longer an independent predictor of survival. Conclusions: Socio-economic differentials in survival from head and neck cancers are determined by a mixture of risk factors, some of which may be amenable to targeted earlier detection methods and lifestyle interventions. However, further research is needed to understand the impacts of performance status in more deprived patients.

FGFR3 mutational status and protein expression in patients with bladder cancer in a Jordanian population - Uncorrected Proof

2010-05-26

Abstract: Bladder cancer accounts for nearly 5% of all newly diagnosed cancers in Jordan, with a much higher frequency in males. Recent studies have shown that activating mutations in FGFR3 are the most common findings in non-invasive low grade bladder tumors. In this study, we, retrospectively, investigated a cohort of 121 bladder cancer patients with various grades and stages of the tumor for molecular changes in FGFR3. Overexpression of FGFR3 was observed in 49%, 34%, 15%, and 2% of pTa, pT1, pT2, and pT3 cases, respectively. Further, FGFR3 expression was positive in 45%, 26%, and 30% of G1, G2 and G3 cases, respectively. Mutational analysis of exons 7, 10 and 15 of FGFR3 identified four previously reported mutations, namely R248C (n=4; 10%), S249C (n=23; 59%), Y375C (n=7; 18%), G382R (n=4; 10%), and one novel mutation, G382E (n=1; 3%). Our results indicate that both mutations and overexpression of FGFR3 are correlated together, and are more prevalent in early stage (pTa and pT1) and low grade (G1 and G2) bladder tumors. Survival analysis showed no contribution of changes in FGFR3 on the patient's survival. Multivariate Cox proportional hazards model analysis of overall survival for the following variables: age, gender, stage and grade of tumor, and FGFR3 (expression and mutation) revealed that age, stage and grade of tumor are independent predictors of OS in patients with bladder cancer. Our work is the first to address the molecular status of FGFR3 in Jordanian patients with bladder cancer, and provides further support for FGFR3 as a key player in the initiation of bladder tumors.

Forecasting age-related changes in breast cancer mortality among white and black US women: A functional data approach - Uncorrected Proof

Farah Yasmeen, Rob J. Hyndman, Bircan Erbas — 2010-05-24

Abstract: The disparity in breast cancer mortality rates among white and black US women is widening, with higher mortality rates among black women. We apply functional time series models on age-specific breast cancer mortality rates for each group of women, and forecast their mortality curves using exponential smoothing state-space models with damping. The data were obtained from the Surveillance, Epidemiology and End Results (SEER) program of the US . Mortality data were obtained from the National Centre for Health Statistics (NCHS) available on the SEER*Stat database. We use annual unadjusted breast cancer mortality rates from 1969 to 2004 in 5-year age groups (45–49, 50–54, 55–59, 60–64, 65–69, 70–74, 75–79, 80–84). Age-specific mortality curves were obtained using nonparametric smoothing methods. The curves are then decomposed using functional principal components and we fit functional time series models with four basis functions for each population separately. The curves from each population are forecast and prediction intervals are calculated. Twenty-year forecasts indicate an overall decline in future breast cancer mortality rates for both groups of women. This decline appears to be steeper among white women aged 55–73 and black women aged 60–84. For black women under 55 years of age, the forecast rates are relatively stable indicating there is no significant change in future breast cancer mortality rates among young black women in the next 20 years.

10-Year risk of colorectal cancer: Development and validation of a prediction model in middle-aged Japanese men - Uncorrected Proof

2010-05-18

Abstract: Background: To estimate an individual's probability of developing colorectal cancer (CRC) may aid health professionals and individuals in improving lifestyle behaviors or deciding the screening regimens. As fewer studies on cancer risk prediction were seen so far, we initially developed an assessment tool with synthesizing key information from a variety of CRC risk factors through a large population-based cohort study. Method: The prediction model was derived from 28,115 men in the Japan Public Health Center-based (JPHC) Prospective Study Cohort II (follow-up: 1993–2005), with risk factors selected by Cox proportion hazard regression. 18,256 men in the JPHC Study Cohort I (follow-up: 1995–2005) were used to evaluate the model's performance. Results: 543 and 398 CRCs were diagnosed during the follow-up period in Cohorts II and I, respectively. The prediction model, including age, BMI, alcohol consumption, smoking status, and the daily physical activity level, showed modest discrimination ability for CRC (C=0.70; 95% confidential interval, 0.68–0.72) in Cohort II and well calibrated in Cohort I (Hosmer–Lemeshow χ2=14.2, P=0.08). Conclusion: The 10-year CRC risk prediction model may be used to estimate CRC risk in Japanese men. It may also play a role in the promotion of CRC prevention strategies.

Cancer survival as a function of age at diagnosis: A study of the Surveillance, Epidemiology and End Results database - Uncorrected Proof

Mena N. Bassily, Richard Wilson, Francesco Pompei, Dimitriy Burmistrov — 2010-04-30

Abstract: Background: Recent research suggested that cancer survival has improved in recent cohorts. Improvement in cancer survival is considered a valid indicator of the quality of care introduced to the patients. The aim of this study is to investigate the changes in the survival profile over age for patients with the most incident cancers. Methods: Survival data of 3.94 million patients diagnosed with 23 primary-site cancers within the periods of 1979–1983, 1989–1993, and 1999–2003 were adopted from the Surveillance, Epidemiology and End Results database. Gender and cause-specific survival probabilities were estimated at one, three, and five years after diagnosis using the Kaplan–Meier survival estimate. Survival was presented for each of the studied cancers, cohorts, and sexes in the form of line graphs as a function of age at diagnosis. Error bars demonstrated the probability of error at 95% confidence level. Results: The graphs demonstrated that cancer survival was improved over the successive cohorts for most cancers, with several exceptions such as brain and lung cancers. The relation between survival and the age at diagnosis was generally described in the form of a gradual decline phase and a rapid fall-off phase at 70–80 years of age, with few exceptions as in leukemia and Hodgkin lymphoma. Patients who survived for three years were more likely to live for five years after diagnosis, but this prediction could not be extrapolated to the one-year survivors. Conclusion: Further studies on tumor-specific characteristics and treatment modalities of these patients are suggested for clarification of the possible causes of variations in patient's survival profile over age.

Fibrous pseudotumors of tunica albuginea, tunica vaginalis and epididymis: Report of two cases - Uncorrected Proof

Serdar Ugras, Cemile Yesil — 2009-11-05

Abstract: We describe two rare cases of fibrous pseudotumor of the paratesticular region. In the first case, five nodules arising from the tunica albuginea of right testicle causing scrotal, enlargement raising after urinary tract infection were seen. In the second case, multiple nodules arising tunica albuginea, tunica vaginalis and epididymis raising after left varicocelectomy operation were observed. The histology showed a paucicellular fibroblastic proliferation of cells within a hyalinized collagenous fibrous stroma containing numerous thin-walled blood vessels accompanied by lymphocytes and plasma cells in tumor tissues in both cases. Tumors in both cases were successfully resected. After operation, both patients had an uneventful recovery without any complications.

African American-preponderant single nucleotide polymorphisms (SNPs) and risk of breast cancer - Uncorrected Proof

Ikuko Kato, Michelle Cichon, Cecilia L. Yee, Susan Land, Jeannette F. Korczak — 2009-11-05

Abstract: Background: African American women more often present with more aggressive types of breast cancer than Caucasian women, but little is known whether genetic polymorphisms specific to or disproportionate in African Americans are associated with their risk of breast cancer. Methods: A population-based case-control study was conducted including 194 cases identified through the Metropolitan Detroit Cancer Surveillance System and 189 controls recruited through random digit dialing to examine polymorphisms in genes involved in estrogen metabolism and action. Results: The African American-specific CYP1A1 5639C allele was associated with an increased risk of breast cancer (odds ratio (OR)=2.34, 95% confidence interval (CI) 1.23–4.44) and this association with the CYP1A1 5639 locus was dependent on another polymorphism in the CYP3A4 gene (P=0.043 for the interaction). In addition, African American-predominant CYP1B1 432 Val allele was significantly more often found in the cases than in the controls overall and the HSD17B1 312 Gly allele was specifically associated with premenopausal breast cancer risk (OR=3.00, 95%CI 1.29–6.99). Conclusion: These observations need to be confirmed in larger studies due to the limited statistical power of the study based on a small number of cases.

Antioxidant activity in essential oils of Cnidium officinale makino and Ligusticum chuanxiong hort and their inhibitory effects on DNA damage and apoptosis induced by ultraviolet B in mammalian cell - Uncorrected Proof

2009-11-05

Abstract: Owing to their high volatile aroma, the dried rhizomes of Cnidium officinale (C. officinale) and Ligusticum chuanxiong (L. chuanxiong) are used as herbal drugs to treat blood pressure depressant, a deficiency disease of antivitamin, inhibition of small intestine sympathetic nerve and as cosmetics for skin care. However, little has been known about the protective effect of their essential oils against ultraviolet B (UVB)-induced DNA damage. In this study, we report antioxidant activity of their essential oils using DPPH and ABTS scavenging assay. In addition, the composition of essential oils was measured by GC/MS. We also investigated whether these essential oils could inhibit UVB-induced DNA damage and apoptosis in the mammalian cell using intracellular DNA migration and expression level of phospho-H2A.X. Twenty constituents in the essential oil were identified and they showed good antioxidant properties, in that IC50 value in DPPH and ABTS showed 6.79 and 7.33μg/ml and 1.58 and 1.58μg/ml in C. officinale and L. chuanxiong. Their treatment inhibited the migration of damaged DNA induced by UV-B; furthermore, they decreased p21 expression and increased cyclin D1 expression as apoptosis-regulatory genes. These results suggest that essential oils in C. officinale and L. chuanxiong may exert inhibitory effects on DNA damage and apoptosis induced by UVB through their high free radical scavenging ability.

Estrogenic activity of bovine milk high or low in equol using immature mouse uterotrophic responses and an estrogen receptor transactivation assay - Uncorrected Proof

2009-11-05

Abstract: Background: Cow's milk contain phytoestrogens especially equol depending on the composition of the feed ration. However, it is unknown whether milk differing in equol exhibits different estrogenicity in model systems and thereby potentially in humans as milk consumers. Methods: The estrogenicity of high and low equol milk (HEM and LEM, respectively) and purified equol was investigated in immature female mice including mRNA expression of six estrogen-sensitive genes in uterine tissue. Extracts of HEM and LEM were also tested for estrogenicity in vitro in an estrogen receptor (ER) reporter gene assay with MVLN. Results: The total content of phytoestrogens was approximately 10 times higher in HEM compared with LEM, but levels of endogenous milk estrone and 17β-estradiol were similar in the two milk types (503–566 and 60–64.6pg/ml, respectively). There was no difference in uterine weight between mice receiving LEM and HEM, and no difference from controls. Equol (50 times the concentration in HEM) was not uterotrophic. The ERβ mRNA expression was down-regulated in the uteri of HEM mice compared with LEM and controls, but there was no difference between milk types for any of the other genes. Extracts of HEM showed a higher estrogenicity than extracts of LEM in MVLN cells, and there was a dose-dependent increase in estrogenicity by equol. Conclusion: The higher in vitro estrogenicity of HEM was not reflected as a higher uterine weight in vivo although the down-regulation of ERβ in uterine tissue of HEM mice could suggest some estrogenic activity of HEM at the gene expression level.