Cancer Epidemiology - Articles in Press

Detection of methylated tissue factor pathway inhibitor 2 and human long DNA in fecal samples of patients with colorectal cancer in China - Uncorrected Proof

2011-05-10

Abstract: Background: To investigate the feasibility of detecting methylated tissue factor pathway inhibitor (TFPI2) and quantifying human long DNA with fluorescent quantitative Alu PCR in fecal DNA as a non-invasive screening tool for colorectal cancer (CRC). Materials and Methods: Methylation-specific PCR (MSP) was performed to analyze TFPI2 gene promoter methylation status in a blinded fashion in stool samples taken from 30 endoscopically diagnosed healthy controls, 20 patients with adenomas, and 60 patients with colorectal cancer. Real-time Alu PCR was used to quantify human long DNA. Results: The specificity of fecal TFPI2 MSP assay and long DNA assay was 100% and 83.3%, respectively. The sensitivity of fecal TFPI2 MSP assay and long DNA assay was 68.3% and 53.3%, respectively. The sensitivity of fecal DNA assay (either marker being positive) was 86.7%, which was high for CRC. Conclusions: Our results have demonstrated the feasibility of using TFPI2 methylation and quantify human long DNA with fluorescent quantitative Alu PCR in fecal samples as a new noninvasive test for CRC.

Does information about risks and benefits improve the decision-making process in cancer screening – Randomized study - Uncorrected Proof

Thomas V. Perneger, Laura Schiesari, Stéphane Cullati, Agathe Charvet-Bérard — 2011-05-09

Abstract: Background: Whether the provision of evidence-based information improves satisfaction with decision-making is unclear. Objective: To examine whether information about risks and benefits of cancer screening leads to a higher satisfaction with the decision that was made. Methods: Randomized mail survey in the general population, among 2333 adults aged 30–60 years. The survey included a hypothetical cancer screening scenario that included varying amounts of information about benefits and risks of screening (factorial randomized design). The decision process was evaluated by a 6 item scale, with scores between 0 (lowest score) and 100 (highest score). Results: Substantial proportions of respondents “completely agreed” that the decision reflected what was most important to them (61.2%), were satisfied with their decision (56.0%), were certain of their decision (54.1%), thought that the best choice for them was obvious (53.5%) and that the decision was easy to make (44.1%). The Cronbach alpha coefficient of the scale was 0.88, the mean score was 82.5, and the standard deviation 17.5. Providing information about benefits increased the decision evaluation score only modestly (+1.1, p=0.11); in contrast, providing information about risks sharply reduced the score (−5.1, p<0.001). Those who refused the screening test had lower scores than those who accepted the screening test (69.2 versus 85.6, p<0.001). Conclusions: Contrary to expectations, informing potential participants about the risks of cancer screening lowered their assessment of the decision process.

Breast-conserving therapy versus modified radical mastectomy: Socioeconomic status determines who receives what—Results from case–control study in Tianjin, China - Uncorrected Proof

2011-05-09

Abstract: Background: Despite anecdotal evidence linking socioeconomic status and choices on surgical management in breast cancer patients in China, no scientific evaluations have ever been conducted. The objective of this study was to evaluate patient factors that influence patients’ treatment options between breast cancer patients receiving breast-conserving therapy (BCT) and modified radical mastectomy (MRM). Methods: A total of 268 stage I–II breast cancer patients treated with BCT in Tianjin Cancer Hospital, from January 2005 to January 2007, were compared with 200 randomly selected breast cancer patients (controls) treated with MRM. A personal health questionnaire (PHQ) was used to assess the factors that may affect the surgical decision making. Chi-squared test and multiple logistic regressions were used to examine factors associated with BCT. Results: BCT patients who were younger and were more likely to live in urban areas had medical insurance, higher levels of education and family income. Patients with medical insurance coverage were approximately six times more likely to receive BCT than patients without medical insurance after controlling for other potentially confounding factors. Similar results were also observed for family income. The observed differences cannot be explained by clinical aspects of their disease, such as tumor stage, estrogen receptor, and lymph node involvement. Conclusion: Breast cancer patients’ socioeconomic status, rather than their clinical condition, is the predominant factor in determining whether a breast cancer patient receives BCT or not. These results provide a snapshot on how socioeconomic status influences cancer care provision in China. Future efforts should be made towards reducing discrepancies in treatment options for cancer patients caused by social class and socioeconomic status.

Quantifying differences in breast cancer survival between England and Norway - Uncorrected Proof

2011-05-06

Abstract: Background: Survival from breast cancer is lower in the UK than in some other European countries. We compared survival in England and Norway by age and time from diagnosis. Methods: We included 303,648 English and 24,919 Norwegian cases of breast cancer diagnosed 1996–2004 using flexible parametric relative survival models, enabling improved quantification of differences in survival. Crude probabilities were estimated to partition the probability of death due to all causes into that due to cancer and other causes and to estimate the number of “avoidable” deaths. Results: England had lower relative survival for all ages with the difference increasing with age. Much of the difference was due to higher excess mortality in England in the first few months after diagnosis. Older patients had a higher proportion of deaths due to other causes. At 5 years post diagnosis, a woman aged 85 in England had probabilities of 0.35 of dying of cancer and 0.32 of dying of other causes, whilst in Norway they were 0.26 and 0.35. By eight years the number of “avoidable” all-cause deaths in England was 1020 with the number of “avoidable” breast cancer related deaths 1488. Conclusion: Lower breast cancer survival in England is mainly due to higher mortality in the first year after diagnosis. Crude probabilities aid our understanding of the impact of disease on individual patients and help assess different treatment options.

Trends in invasive breast cancer incidence among French women not exposed to organized mammography screening: An age-period-cohort analysis - Uncorrected Proof

Jean-François Viel, Raouchan Rymzhanova, Evelyne Fournier, Arlette Danzon — 2011-05-04

Abstract: Background: The long tenure of the Doubs cancer registry (France) and the late implementation of a mass screening program provide a unique opportunity to assess the relative contributions of age, period and cohort effects to the increase in female invasive breast cancer incidence, while avoiding the influence of an organized screening program. Methods: Population and incidence data were provided for the Doubs region during the 1978–2003 period. Breast cancer counts and person-years were tabulated into 1-year classes by age and time period. Age-period-cohort models with parametric smooth functions were fitted to the data, assuming a Poisson distribution for the number of observed cases. Results: A total of 5688 incident cases of invasive breast cancer in women were diagnosed in women aged 30–84 years in the Doubs region between 1978 and 2003. The annual percentage increase in incidence is 2.09%. Age effects rise dramatically until age 50, and at a slower pace afterwards. Large cohort curvature effects (p<10−6), show departure from linear trends, with a significant peak for women born around 1940. Period curvature effects are lower in magnitude (p=0.01). Conclusion: Both cohort and period effects are involved in the marked increase in breast cancer incidence over a 25-year period in the Doubs region. Although the future trend for breast cancer incidence is difficult to predict, the introduction of an organized screening program, and the sharp decline in hormone replacement therapy use will likely contribute to period effects in future analyses.

Assessment of follow-up, and the completeness and accuracy of cancer case ascertainment in three areas of India - Uncorrected Proof

2011-05-03

Abstract: Background: A prospective study of diet and cancer has not been conducted in India; consequently, little is known regarding follow-up rates or the completeness and accuracy of cancer case ascertainment. Methods: We assessed follow-up in the India Health Study (IHS; 4671 participants aged 35–69 residing in New Delhi, Mumbai, or Trivandrum). We evaluated the impact of medical care access and relocation, re-contacted the IHS participants to estimate follow-up rates, and conducted separate studies of cancer cases to evaluate registry coverage (604 cases in Trivandrum) and the accuracy of self- and proxy-reporting (1600 cases in New Delhi and Trivandrum). Results: Over 97% of people reported seeing a doctor and 85% had lived in their current residence for over six years. The 2-year follow-up rate was 91% for Trivandrum and 53% for New Delhi. No cancer cases were missed among public institutions participating in the surveillance program in Trivandrum during 2003–2004; but there are likely to be unmatched cases (ranging from 5 to 13% of total cases) from private hospitals in the Trivandrum registry, as there are no mandatory reporting requirements. Vital status was obtained for 36% of cancer cases in New Delhi as compared to 78% in Trivandrum after a period of 4 years. Conclusions: A prospective cohort study of cancer may be feasible in some centers in India with active follow-up to supplement registry data. Inclusion of cancers diagnosed at private institutions, unique identifiers for individuals, and computerized medical information would likely improve cancer registries.

No association of XRCC1 polymorphisms Arg194Trp and Arg399Gln with colorectal cancer risk - Uncorrected Proof

2011-04-13

Abstract: Background: X-ray repair cross complementation group 1 (XRCC1) plays a key role in base excision repair. The purpose of this study was to examine the association of two genetic polymorphisms in XRCC1 (rs1799782 and rs25487) with risk of colorectal polyps and colorectal cancer (CRC). Methods: In the ongoing colorectal cancer study of Austria (CORSA), a total of 3091 Caucasian participants was genotyped using 5′-nuclease TaqMan assays. Multiple logistic regression was applied to compare individuals of the control group against three different case groups namely CRC cases, high-risk and low-risk polyps. Results: The two investigated SNPs in XRCC1 were not found to be associated neither CRC risk nor polyp risk. Comparing the CRC cases versus the controls the OR was 0.60 (95%CI 0.27–1.31) for the heterozygous polymorphic genotype of SNP rs1799782 and 1.47 (95%CI 0.81–2.65) for the homozygous polymorphic genotype of SNP rs25487. Comparing the high-risk polyp group versus the controls the OR was 2.64 (95%CI 0.61–11.42) for the homozygous polymorphic genotype of SNP rs1799782 and 0.89 (95%CI 0.60–1.33) for SNP rs25487, respectively. In an haplotype analysis also no statistically significant association was found. Conclusion: Our finding that none of the two investigated SNPs of XRCC1 were significantly associated with risk of CRC or polyps is consistent with the results of a recently published meta-analysis.

Sun exposure, vitamin D receptor polymorphisms FokI and BsmI and risk of multiple primary melanoma - Uncorrected Proof

2011-04-04

Abstract: Sunlight exposure increases risk of melanoma. Sunlight also potentiates cutaneous synthesis of vitamin D, which can inhibit melanoma cell growth and promote apoptosis. Vitamin D effects are mediated through the vitamin D receptor (VDR). We hypothesized that genetic variation in VDR affects the relationship of sun exposure to risk of a further melanoma in people who have already had one. We investigated the interaction between VDR polymorphisms and sun exposure in a population-based multinational study comparing 1138 patients with a multiple (second or subsequent) primary melanoma (cases) to 2151 patients with a first primary melanoma (controls); essentially a case–control study of melanoma in a population of melanoma survivors. Sun exposure was assessed using a questionnaire and interview, and was shown to be associated with multiple primary melanoma. VDR was genotyped at the FokI and BsmI loci and the main effects of variants at these loci and their interactions with sun exposure were analyzed. Only the BsmI variant was associated with multiple primary melanoma (OR=1.27, 95% CI 0.99–1.62 for the homozygous variant genotype). Joint effects analyses showed highest ORs in the high exposure, homozygous variant BsmI genotype category for each sun exposure variable. Stratified analyses showed somewhat higher ORs for the homozygous BsmI variant genotype in people with high sun exposure than with low sun exposure. P values for interaction, however, were high. These results suggest that risk of multiple primary melanoma is increased in people who have the BsmI variant of VDR.

Epidemiology of gastrointestinal stromal tumours: Single-institution experience and clinical presentation over three decades - Uncorrected Proof

2011-03-28

Abstract: Background: Epidemiology of gastrointestinal stromal tumour (GIST) is sparsely described. We report a population-based consecutive case series of GIST over three decades from southwestern Norway. Methods: All mesenchymal tumours registered at Stavanger University Hospital between 1980 and 2009 were reviewed and those of the gastrointestinal tract were reclassified with regard to histomorphology and/or immunohistochemistry profiles consistent with GIST. Reported are patients’ characteristics and GIST incidence and prevalence estimated using population statistics. Results: Fifty-two cases were identified; 62% of the patients were women. Median age at diagnosis was 67 years. Fifty-eight percent of the tumours were located in the stomach, 38% in the small bowel and one each in colon and rectum. One third were considered to be high risk according to the NIH consensus criteria. The crude incidence rate of GIST was 1.8 per million in the study population per year in the 5-year period 1980–1984, and increased to around 6 in the following years with a peak at 12.5 per million in 2000–2004. The over all crude incidence rate for 1980–2009 was 6.5 per million (95% CI 4.8–8.3 per mill.). Standardized age- and gender adjusted incidence for Norway was 7.4 per million (95% CI 5.4–9.4). The number of patients alive with GIST increased over the study period, with a peak in 2000–2004 at 92.1 per million (95% CI 60.7–134.0 per mill.). One in five had an additional gastrointestinal cancer, located in the colon (n=6), rectum (n=2), stomach (n=3) or, pancreas (n=1). Conclusion: Incidence of GIST in the south-western part of Norway is relatively stable and towards the lower end of the range reported in the worldwide literature. An increasing prevalence likely reflects therapy effects. Synchronous gastrointestinal cancers are relatively common in patients with GIST.

Obesity, metabolic syndrome and esophageal adenocarcinoma: Epidemiology, etiology and new targets - Uncorrected Proof

2011-03-21

Abstract: Background: Rates of distal and junctional adenocarcinomas are increasing in Western countries.Methods: Systematic review of epidemiological evidence linking obesity to esophageal adenocarcinoma (EA) was performed for studies published from 2005 to 2010. The current understanding of obesity's role in the etiology and potential dysplastic progression of Barrett's esophagus (BE) to EA is reviewed.Results: Accumulating epidemiological studies provide evidence of obesity's role as a driving force behind the increasing rates of EA. The simplest construct is that obesity promotes reflux, causing chronic inflammation and BE, predisposing to adenocarcinoma. However, as obesity is positively associated with the prevalence of many cancers, other mechanisms are important. A link may exist between fat distribution patterns and the risk of BE and EA. Altered metabolic profiles in the metabolic syndrome (MetS) may be a key factor in cell cycle/genetic abnormalities that mark the progression of BE towards cancer. Research highlighting a unique role of MetS in the length of BE, and its association with systemic inflammation and insulin resistance is discussed, as well as adipokine receptor expression in both BE and esophageal epithelium, and how MetS and the systemic response impacts on key regulators of inflammation and tumorigenesis.Conclusions/impact: Obesity is positively associated with EA. The systemic inflammatory state consequent on the altered metabolism of obese patients, and the associated impact of adipocytokines and pro-coagulant factors released by adipocytes in central fat, may underlie obesity's relationship to this cancer. Novel therapeutic agents that may antagonize adipo-cytokines and potentially offer a promising role in cancer therapy are discussed.

Prevalence of Helicobacter pylori genotypes (vacA, cagA, cagE and virB11) in gastric cancer in Brazilian's patients: An association with histopathological parameters - Uncorrected Proof

2011-03-21

Abstract: Purpose: To investigate the frequency and the association of vacA alleles, cagA, cagE and virB11 genes of Helicobacter pylori from patients with gastric cancer, considering the clinic histopathological parameters. Methods: One hundred and one gastric adenocarcinoma tissues were assessed by PCR to detect H. pylori and vacA alleles, cagA, cagE and virB11. Results: The distribution of cases according to the presence of the genes studied showed that the group containing vacA s1m1, cagA, cagE and virB11 H. pylori genes was significantly more frequent, followed by the group with at least one marker on the right side and left of the island. They were also present in the early stages and were the most frequent in nearly all histopathological grades. Conclusions: This study verified that vacAs1m1 and cag-PAI genes, cagA, cagE and virB11 are important H. pylori markers for gastric cancer development. Also, this study corroborates the importance of cagE and cagA together as cag-PAI marker.

Gender differences in the incidence of laryngeal and hypopharyngeal cancers in Spain - Uncorrected Proof

Dyego Leandro Bezerra de Souza, María Milagros Bernal Pérez, Maria Paula Curado — 2011-03-17

Abstract: Objective: The present ecological study analyzed gender differences in the incidences and trends of laryngeal and hypopharyngeal cancers in Spain and compared these with smoking prevalence and alcohol consumption in the period. Methods: Data were evaluated from seven Spanish Population-Based Cancer Registries, selected with a minimum follow-up period of 10years. Information on smoking prevalence and trends were collected from National Health Surveys; for alcohol consumption the Global Alcohol Database was utilized. Trends in the incidences of cancer, smoking and alcohol consumption were analyzed by log-linear joinpoint regression. Results: Analysis of the seven groups of registries revealed a statistically significant reduction in the incidence of laryngeal cancer in men (APC=−4.2) over time and a non-significant increase in women (APC=0.6), with data on prevalence of smoking revealing similar trends. For hypopharyngeal cancer in men an initial increase of 10.6% per year was observed, followed by a reduction of −7.2%; however in women a constant increase of 2.8% per year was observed in the evaluated period. Conclusions: In recent years, the incidence of laryngeal and hypopharyngeal cancers have increased in Spanish women and decreased in Spanish men, narrowing the gap between genders for this neoplasm. The identified trends are probably related to the consumption of tobacco and alcohol; however other risk factors should also be addressed.

Recovering circulating extracellular or cell-free RNA from bodily fluids - Uncorrected Proof

2011-03-16

Abstract: The presence of extracellular circulating or cell-free RNA in biological fluids is becoming a promising diagnostic tool for non invasive and cost effective cancer detection. Extracellular RNA or miRNA as biological marker could be used either for the early detection and diagnosis of the disease or as a marker of recurrence patterns and surveillance. In this review article, we refer to the origin of the circulating extracellular RNA, we summarise the data on the biological fluids (serum/plasma, saliva, urine, cerebrospinal fluid and bronchial lavage fluid) of patients suffering from various types of malignancies reported to contain a substantial amount of circulating extracellular (or cell-free) RNAs and we discuss the appropriate reagents and methodologies needed to be employed in order to obtain RNA material of high quality and integrity for the majority of the experimental methods used in RNA expression analysis. Furthermore, we discuss the advantages and disadvantages of the RT-PCR or microarray methodology which are the methods more often employed in procedures of extracellular RNA analysis.

Reply to: Lost opportunity to usefully examine French breast cancer screening mortality - Uncorrected Proof

Zoe Uhry, G. Hédelin, M. Colonna, S. Duffy — 2011-03-14

Essentially, Professor Braillon and Dr Bewley called for an entirely different paper, rather than making specific criticisms . Their main complaints were: (1) their poor opinion of the methodology; (2) we did not made a breast cancer mortality trends analysis; (3) absence of evaluation of harms of screening.

The role of mammography screening attendance and detection mode in predicting breast cancer survival-Is there added prognostic value? - Uncorrected Proof

Cornelis Biesheuvel, Kamila Czene, Chantal C. Orgeás, Per Hall — 2011-03-07

Abstract: Introduction: The aim of this study was to examine whether screening exposure status, defined as detection mode (screening, interval or symptomatic) combined with breast cancer screening attendance prior to diagnosis, had any additional value over detection mode in predicting breast cancer survival. We also assessed the effect of hormone replacement therapy (HRT) on the association of detection mode with breast cancer survival.Methods: We analysed and compared the associations of both screening exposure status and detection mode with 5-year breast cancer survival on a cohort of 3013 breast cancer patients, aged 50–74 years in Sweden. We used Cox proportional hazards modelling with adjustments for tumour size, grade, estrogen receptor (ER) and progesterone receptor (PR) status and lymph node involvement. We repeated the analyses after stratification for HRT use.Results: Multivariate hazard ratios (HR) for cancers detected in patients at subsequent screens, interval cancers and symptomatic cancers in patients with and without previous screening attendance were 1.3 (95%CI 0.7–2.3), 1.8 (95%CI 1.0–3.2), 1.8 (95%CI 0.9–3.6) and 2.2 (95%CI 1.2–4.1) respectively, compared with cancers detected at the first screen. The regression model including screening exposure status had no additional prognostic value over the model including detection mode (P=0.63). HRT users showed a more favourable survival than non-users; this was not influenced by detection mode.Conclusion: The number of routine screening examinations attended in the 5-year period prior to diagnosis had no additional prognostic value over detection mode in predicting breast cancer survival.

The enduring and evolving relationship between social class and breast cancer burden: A review of the literature - Uncorrected Proof

Ann C. Klassen, Katherine C. Smith — 2011-03-07

Abstract: Introduction: Breast cancer in women has historically been seen as a “cancer of affluence” and there is a well-documented higher incidence among women of higher social class, as well as in societies with higher resources. However, the relationship between social class and breast cancer disease characteristics, especially those associated with poorer prognosis, is less well documented, and the overall relationship between breast cancer mortality and social class has been shown to vary. Furthermore, rapid changes in women's health and health-related behaviors in societies around the world may have an impact on both incidence and mortality patterns for breast cancer in the future. Methods: A PUBMED search on breast cancer and social class (incorporating the MeSH-nested concept of SES) yielded 403 possible studies published between 1978 and 2009, of which 90 met criteria for review. Our review discusses conceptualization and measurement of women's social class in each study, as well as findings related to breast cancer incidence, tumor biology or mortality, associated with social class. Findings: We found mostly consistent evidence that breast cancer incidence continues to be higher in higher social class groups, with some modification of risk with adjustment for known risk factors, including physical activity and reproductive history. However, biologic characteristics associated with poorer prognosis were negatively associated with social class (i.e., greater occurrence among disadvantaged women), and mortality from breast cancer showed inconsistent relationship to social class. Conclusions: We discuss these studies in relation to the growing burden of breast cancer among low resource groups and countries, and the need for cancer control strategies reflecting the emerging demographics of breast cancer risk.

The Western Australian Melanoma Health Study: Study design and participant characteristics - Uncorrected Proof

2011-03-07

Abstract: Background: Cutaneous malignant melanoma is a major public health issue in Australia and other nations. A greater understanding of the genetic determinants and their interactions with environmental factors may lead to better interventions and control of the disease. The Western Australian Melanoma Health Study (WAMHS) is a population-based case-collection and biospecimen resource established to investigate the genetic epidemiology of melanoma. This manuscript discusses the design of the WAMHS and the characteristics of the participants. Methods: Participants were recruited through the Western Australian Cancer Registry, which is notified of all incident cancers in the state of Western Australia by law. Once the diagnosing doctor's consent was obtained, all eligible, resident Western Australian, adult cases of melanoma diagnosed between January 2006 and September 2009, were contacted by mail and invited to participate. Clinical, questionnaire-based phenotypic and blood samples for extraction of DNA, RNA and serum were collected from consenting cases. Clinical data consisted of all pathological data recorded by the cancer registry and the questionnaire, administered by telephone interview, covered major risk factors for melanoma, such as sun exposure history and skin type. Results: The final sample consisted of 1643 consenting cases out of 3420 cancer notifications (48.04%), of which 1455 cases completed one or more components of the study and 1157 completed all components. The WAMHS sample differed to all melanoma notifications only in age, with a bias towards older individuals (P<0.0001). No significant differences were observed in sex, melanoma site, Breslow thickness or Clark's level. Conclusions: The WAMHS study is novel in its non-family based approach and focus on common (low penetrance) genetic determinants. This comprehensive resource will enable further steps to be taken towards understanding the complex pathways involved in melanoma.

Physical activity reduces breast cancer risk: A case–control study in Tunisia - Uncorrected Proof

2011-03-07

Abstract: Purpose: This study examined the relationship between lifetime history of physical activity and breast cancer risk. 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. Odds ratios (ORs), 95% confidence intervals (CI) and a full confounding assessment, included in this analysis, were derived using logistic regression. 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.

Predicted incidence of oral cavity, oropharyngeal, laryngeal, and hypopharyngeal cancer in Spain and implications for cancer control - Uncorrected Proof

Dyego Leandro Bezerra de Souza, María Milagros Bernal Pérez, Maria Paula Curado — 2011-03-07

Abstract: Objective: This paper presents predictions of incidence rates of the most common cancers in the head and neck regions for the period 2003–2017, grouped in periods of five years (2003–2007, 2008–2012, 2013–2017), based on incidence data from five Population-Based Cancer Registries in Spain. Methods: Cancer registries published in Cancer Incidence in Five Continents vols. VII–IX with a minimum of 15 years of continuous data were selected. The selected topographies were: oral cavity, oropharynx, larynx and hypopharynx. Predictions were made using the Nordpred program, utilizing the age–period–cohort model. Results: For the period between 2013 and 2017, 4542 cases of head and neck cancers were predicted for men and 810 for women, with a proportion of 5.6 men to one woman. Cancers of the oral cavity, larynx and hypopharynx in men presented an increasing number of cases due to demographic changes, but the risk will be reduced by 2% for oral cavity cancer, 28% for laryngeal cancer, 3% for hypopharyngeal cancer and 4% for grouped locations. Oropharyngeal cancer in men has a predicted increase of 47% due to risk. Predictions for the female gender suggest an increment in all locations, with an increased risk of 24% for the oral cavity, 37% for the larynx, and 67% for grouped locations. Conclusion: Predictions show a reduction in gender difference in the incidence of head and neck cancers. There was a reduction in incidence rates for men and an increase for women, evidencing changes in exposure to tobacco and alcohol.

Early evaluation of an organised mammography screening program in Greece 2004–2009 - Uncorrected Proof

2011-03-07

Abstract: Objective: The aim of the current study was to present early performance indicators of a breast cancer screening program in Greece.Methods: Between March 2004 and July 2009, 9621 women aged between 40 and 69years were recruited into programme on a voluntary basis. The participating women were residents of two adjacent administrative regions of Greece. Several performance indicators were calculated for the first and subsequent screen, separately.Results: A total of 9621 mammograms were 1st screens and 4462 were subsequent screens. The attendance rate was almost 1.5%. The technical repeat rate was 1.7%. On the 1st screen, the recall rate was 11.4%, while the recall rate of the subsequent screens was 5.5%. The vast majority of detected cancers were invasive and only the 1/7 of cancers was identified as DCIS. As concerns tumour size of invasive cancers, the 1.9% and 16.7% was unknown, in the first and subsequent screen, respectively. Moreover, 38.5% and 44.4% of cancers detected in the 1st and subsequent screen, respectively, were less than 15mm in diameter. Almost 1/5 of diagnosed cancers were interval cancers.Conclusions: This breast cancer screening programme is the first one in Greece and the attendance rate is extremely low. Taking into account that an organised screening programme may benefit women with a reduction in breast cancer mortality, there is an urgent need to develop a national-based screening programme, to increase participation and to improve the information system used to monitor programme performance.

Diabetes and urothelial cancer risk: The Multiethnic Cohort Study - Uncorrected Proof

2011-03-07

Abstract: Background: It is important to understand the adverse health sequelae that may result from the rising incidence of diabetes. Diabetics may have an increased risk for urothelial cancer but the evidence from prospective studies and ethnically diverse populations is sparse. Method: We examined this association in the Multiethnic Cohort (MEC) that was conducted in Hawaii and Los Angeles with nearly 186,000 participants in five ethnic groups. Over a median 10.7 years of follow-up, 918 incident cases of urothelial cancer (89% bladder and 11% other urinary tract sites) were identified through tumor registry linkages. Results: A self-reported diagnosis of diabetes was associated with an increased risk of urothelial cancer (relative risk=1.25; 95% confidence interval: 1.04–1.50). The association was not explained by body mass index, physical activity, or smoking. There was some suggestion that the risk was higher in women, Whites and African Americans, and past smokers. The risk associated with diabetes for in situ and localized cancer was similar to that for regional and distant cancer. Conclusion: This study demonstrates that the increased urothelial cancer risk with diabetes in this multiethnic population is very similar to that observed in mostly White or Asian populations. Whether or not the elevated risk is moderated by the degree of control of the hyperglycemia associated with diabetes will need to be determined in future studies.

Disparities in survival of stomach cancer among different socioeconomic groups in North-East Netherlands - Uncorrected Proof

2011-03-07

Abstract: Background: Survival differences in stomach cancer are depended on patient, tumour and treatment factors. Some populations are more prone to develop stomach cancer, such as people with low socioeconomic status (SES). The aim of this population based study was to assess whether differences in socioeconomic status (SES) alone, after adjusting for confounding factors, also influence survival. Methods: From 1989 to 2007 all patients with stomach cancer were selected from the cancer registry of the Comprehensive Cancer Centre North-East. Postal code at diagnosis was used to determine SES, dividing patients in three groups; low, intermediate and high SES. Associations between age, localization, grade, stage, and treatment were determined using Chi-square analysis. Relative survival analysis was used to estimate relative excess risk (RER) of dying according to SES. Results: In low SES neighbourhoods diagnosis was established at older age. More distal tumours were detected in patients with low SES, whereas pathology showed more poorly differentiated tumours in patients with high SES. Overall, more resections were performed in, and more chemotherapy was administrated to patients in high SES neighbourhoods. After adjusting for confounding factors, the risk of dying was lower for patients with high SES (RER 0.89, 95% Confidence Interval 0.81–0.98) compared to patients with low SES. Conclusion: SES proved to be an independent prognostic factor for survival in patients with stomach cancer.

Lost opportunity to usefully examine French breast cancer screening mortality - Uncorrected Proof

Alain Braillon, Susan Bewley — 2011-02-28

Uhry et al. use a Markov decision analysis to provide broad estimates for the effect of organised breast cancer screening on mortality in France. The methodology is inappropriate and the conclusion misleads .

Marital status and colon cancer outcomes in US Surveillance, Epidemiology and End Results registries: Does marriage affect cancer survival by gender and stage? - Uncorrected Proof

Li Wang, Sven E. Wilson, David B. Stewart, Christopher S. Hollenbeak — 2011-02-24

Abstract: Background: Marital status has been associated with outcomes in several cancer sites including breast cancer in the literature, but little is known about colon cancer, the fourth most common cancer in the US. Methods: A total of 127,753 patients with colon cancer were identified who were diagnosed between 1992 and 2006 in the US Surveillance, Epidemiology and End Results (SEER) Program. Marital status consisted of married, single, separated/divorced and widowed. Chi-square tests were used to examine the association between marital status and other variables. The Kaplan–Meier method was used to estimate survival curves. Cox proportional hazards models were fit to estimate the effect of marital status on survival. Results: Married patients were more likely to be diagnosed at an earlier stage (and for men also at an older age) compared with single and separated/divorced patients, and more likely to receive surgical treatment than all other marital groups (all p<0.0001). The five-year survival rate for the single was six percentage points lower than the married for both men and women. After controlling for age, race, cancer stage and surgery receipt, married patients had a significantly lower risk of death from cancer (for men, HR: 0.86, CI: 0.82–0.0.90; for women, HR: 0.87, CI: 0.83–0.91) compared with the single. Within the same cancer stage, the survival differences between the single and the married were strongest for localized and regional stages, which had overall middle-range survival rates compared to in situ or distant stage so that support from marriage could make a big difference. Conclusions: Marriage was associated with better outcomes of colon cancer for both men and women, and being single was associated with lower survival rate from colon cancer.

The validity of self-reported cancer diagnoses and factors associated with accurate reporting in a cohort of older Australian women - Uncorrected Proof

Efty Stavrou, Claire M. Vajdic, Deborah Loxton, Sallie-Anne Pearson — 2011-02-24

Abstract: Epidemiological research often ascertains cancer history via self-reported questionnaires. We assessed the validity of self-reported cancer diagnoses in women born 1921–1926 recruited to the Australian Longitudinal Study in Women's Health (ALSWH) and determined the factors associated with false positive (FP) and false negative (FN) reporting. 4234 ALSWH cohort members were asked at baseline (1996) and in subsequent three-yearly surveys whether they had been diagnosed with specific cancers, including breast, cervical, lung and colorectal. We linked the cohort to the population-based New South Wales Central Cancer Registry (CCR) from 1972 to 2005 to identify registered invasive cancers. We calculated sensitivity, specificity and positive predictive value (PPV) of self-reported cancer diagnoses overall, at baseline (prevalent cancers) and follow-up (incident cancers) using the CCR diagnosis as the ‘gold standard’. We used adjusted logistic regression to examine the determinants of FP and FN reports. Overall sensitivity was 89.2% (95% CI 86.0–91.7%) and exceeded 90% for breast, lung and colorectal cancer at baseline. Overall specificity was 96.9% (95% CI 96.3–97.5%), however, PPV was lower at 66.5% (95% CI 62.7–70.1%). FN reporting of any cancer at baseline was associated with being born overseas. Sensitivity and specificity of self-reported cancer diagnoses in this cohort of older women (aged 70–75 years at baseline) is high but PPV is comparatively lower. Hence, the use of linked data from population-based cancer registries is recommended for studies of cancer epidemiology. Particular attention must also be paid to country of birth in self-reported cancer data, as these findings suggest cancer will be under-reported by this group of women.

Biochemical-markers for the diagnosis of bone metastasis: A review in clinical - Uncorrected Proof

Qian Huang, Xuenong Ouyang — 2011-02-21

Abstract: The preferential metastasis of cancer cells to skeleton not only disrupts the process of bone remodeling and influences the therapeutic decision, but also results in severe complications. Although the current diagnosis of bone metastases (BM) relies on bone imaging techniques, they are not sensitive enough for early detection as well as they are invasive and expensive to use. Since factors derived from bone metabolism are potentially useful to diagnose metastatic bone disease in cancer patients, a number of clinical trials have been carried out on this area. Results suggest that higher levels of bone biomarkers are associated with an increased risk of BM. As a result, biochemical-markers are showing prospects in early diagnosis of BM. This review summarizes the available evidence on the clinical use of biochemical-markers in the diagnosis of various cancers with high incidence of BM including breast, prostate and lung.

Association of functional −509C>T polymorphism in the TGF-β1 gene with infiltrating ductal breast carcinoma risk in a Russian Western Siberian population - Uncorrected Proof

2011-02-21

Abstract: Background: Transforming growth factor β1 (TGF-β1) is a multifunctional cytokine that plays an important role in human mammary carcinogenesis. The purpose of this study was to investigate the association between −509C>T single nucleotide polymorphism (SNP) of the TGF-β1 gene and infiltrating ductal breast carcinoma risk in Russian patients of Western Siberian region. Materials and methods: Blood samples collected from 218 women with histologically confirmed infiltrating ductal breast carcinoma and 290 healthy female controls were analyzed through polymerase chain reaction–restriction fragment length polymorphism methods. Results: The −509TT genotype was significantly associated with a decreased risk for ductal breast carcinoma (OR=0.47, CI: 0.26–0.82, P=0.004). Similarly, the −509T was significantly less in ductal breast cancer patients (34.4%) than in control individuals (41.6%; OR=0.74, CI: 0.57–0.96, P=0.02). With the exception of association between the −509TT genotype and large tumor size (P=0.01), there was no significant association between the studied polymorphism and clinicopathological characteristics. Conclusion: The results of this study suggest that polymorphism of TGF-β1 −509C>T gene may modify individual susceptibility to infiltrating ductal breast carcinoma in Russian women of Western Siberian region.

Prevalence and prognosis of synchronous colorectal cancer: A Dutch population-based study - Uncorrected Proof

2011-02-17

Abstract: Background: A noticeable proportion of colorectal cancer (CRC) patients are diagnosed with synchronous CRC. Large population-based studies on the incidence, risk factors and prognosis of synchronous CRC are, however, scarce, and are needed for better determination of risks of synchronous CRC in patients diagnosed with colonic neoplasia. Methods: All newly diagnosed CRC between 1995 and 2006 were obtained from the Rotterdam Cancer Registry in The Netherlands, and studied for synchronous CRC. Results: Of the 13,683 patients diagnosed with CRC, 534 patients (3.9%) were diagnosed with synchronous CRC. The risk of having synchronous CRC was significantly higher in men (OR 1.54, 95% CI 1.29–1.84) and in patients aged >70years (OR 1.83, 95% CI 1.39–2.40). Synchronous CRC patients had a significantly higher risk of distant metastases (OR 1.69, 95% CI 1.27–2.26). In 34% (184/534) the two tumours were located in different surgical segments. Five-year relative survival of synchronous CRC was similar to patients with solitary CRC after multivariate adjustment for the presence of distant metastases. Conclusion: One out of 25 patients diagnosed with CRC presents with synchronous CRC. In the multivariate analysis, survival of patients with synchronous CRC was similar to patients with solitary CRC, when corrected for the presence of distant metastases at first presentation. One third of the synchronous CRC were located in different surgical segments, which stresses the importance of performing total colon examination preferably prior to surgery.

Pediatric germ cell tumors and parental infertility and infertility treatment: A Children's Oncology Group report - Uncorrected Proof

Susan E. Puumala, Julie A. Ross, Melanie M. Wall, Logan G. Spector — 2011-02-17

Abstract: Background: Few risk factors have been established for childhood germ cell tumors (GCT). Parental infertility and infertility treatment may be associated with GCT development but these risk factors have not been fully investigated.Methods: A case–control study of childhood GCT was conducted through the Children's Oncology Group (COG). Cases, under the age of 15 years at diagnosis, were recruited through COG institutions from January 1993 to December 2002. Controls were obtained through random digit dialing. Information about infertility and infertility treatment along with demographic factors was collection through maternal interviews. Subgroups created by gender, age at diagnosis, and tumor location were examined separately. Statistical analysis was performed using multivariate logistic regression models.Results: Overall, no association between GCT and infertility or its treatment was found. In subgroup analysis, females whose mothers had two or more fetal losses were found to be at increased risk for non-gonadal tumors (Odds ratio (OR)=3.32, 95% Confidence interval (CI)=1.12–9.88). Younger maternal age was associated with a lower risk of gonadal GCT in females (OR=0.52, 95% CI=0.28–0.96). There was an increased risk of all GCT and gonadal GCT in males born to older mothers (OR=2.88, 95% CI=1.13–7.37 and OR=3.70, 95% CI=1.12–12.24).Conclusion: While no association between parental infertility or its treatment and childhood GCT was found overall, possible associations with maternal age and history of recurrent fetal loss were found in subgroups defined by gender.

Estimation of premature mortality from oral cancer in Japan, 1995 and 2005 - Uncorrected Proof

2011-02-17

Abstract: Background: To better understand the picture of premature death from oral cancer, we estimated years of life lost (YLL) and average years of life lost (AYLL) of this cancer for the years 1995 and 2005 in Japan. Methods: We obtained the mortality data for 5-year age groups from the Vital Statistics of Japan for the years 1995 and 2005, an interval of 10 years. Age-standardized rates (ASRs) per 100,000 persons were calculated for each subset of oral cancer death. We estimated YLL and AYLL according to life tables in Japan to reflect premature mortality. Results: For both men and women combined, 4099 and 5679 deaths due to oral cancer were recorded for the years 1995 and 2005. In men, cancer of tongue, oropharynx, and hypopharynx were the most frequently observed anatomic sites. We observed a total of 51,339.1 years of life lost in 1995 and 68,630.4 years in 2005, corresponding to an overall AYLL for all cancer deaths combined of 17.2 and 16.5 years earlier than life expectancy, respectively. The greatest AYLL was seen for deaths from nasopharyngeal cancer, with AYLL of 21.1 years in 1995 and 20.3 years in 2005. In women, cancer of the tongue and gum were the most affected anatomic sites. Total numbers of YLL were 18,884.8 years in 1995 and 24,765.7 in 2005, corresponding to an overall AYLL of 16.9 and 16.2 years earlier than life expectancy. The greatest AYLL was seen for deaths from nasopharyngeal cancer, with AYLL of 22.4 years and 20.4 years in 1995 and 2005, respectively. Conclusion: The present study shows that cancer of pharynx, tongue, and gum were the most frequent oral cancers in both sexes in both 1995 and 2005, and responsible for a remarkable number of years of life expectancy lost. Deaths due to those cancer sites occurred about 16–21 years earlier than expected in men, and 14–22 years in women.

Lack of replication for the association between HER2 I655V polymorphism and breast cancer risk: A systematic review and meta-analysis - Uncorrected Proof

Issa J. Dahabreh, Samuel Murray — 2011-02-03

Abstract: Background: Multiple epidemiological studies have investigated rs1136201, a non-synonymous polymorphism of the human epidermal growth factor receptor-2 gene (HER2) resulting in the substitution of valine for isoleucine at codon 655 (Ile655Val) of the HER2 protein, as a risk factor for breast cancer. Methods: We searched multiple databases to identify genetic association studies investigating the effect of rs1136201 on breast cancer risk. For each study we calculated unadjusted odds ratios with their variance under additive, dominant, recessive and allele-frequency genetic models. Summary odds ratios (OR) with their corresponding confidence interval (CI) were calculated using random effects models. Results: Based on the 33 case–control studies reporting data for the additive genetic model (20,461 cases/23,832 controls) we did not find evidence of an association between rs1136201 and breast cancer, OR=1.05 (95% CI, 0.99–1.11), with significant between-study heterogeneity (pQ<0.001; I2=49%). Smaller studies produced more extreme results compared to larger studies (p=0.001). Studies in which genotyping was not blind to case–control status (p=0.01), studies not reporting the use of genotyping quality control (p=0.01), and studies using RFLP-based methods (p=0.01) produced significant associations. Meta-regression results confirmed that there was a significant interaction between lack of quality control (p=0.04) and lack of blinding (p=0.04) and the genetic effect of rs1136201 on breast cancer risk. Conclusions: It is unlikely that HER2 rs1136201 is a risk factor for breast cancer. Laboratory artifacts, lack of genotyping quality control or blinding and publication bias appear to have influenced the results published to date and need to be addressed in the design of future studies.

Trends in breast cancer survival in Germany from 1976 to 2008—A period analysis by age and stage - Uncorrected Proof

Bernd Holleczek, Volker Arndt, Christa Stegmaier, Hermann Brenner — 2011-01-31

Abstract: Background: Implementation of mammography screening and advances in breast cancer treatment are considered as main reasons for the decline in breast cancer mortality observed in many industrialized countries during the past two decades. The purpose of this study was to provide a comprehensive assessment of trends in breast cancer incidence, mortality and survival by age and stage in Germany. Methods: Data from the population based Saarland Cancer Registry including patients diagnosed with breast cancer from 1972 to 2007 were used. Period analysis methods were employed to calculate 5-year relative survival and its trends. Results: Mortality started to decline during the 1990s, and a previous increase in incidence levelled off in the early 21st century. Overall age-standardized 5-year relative survival of invasive breast cancer steadily increased during the past three decades to 83% in 2004–2008. This increase was mostly due to an increase in survival for patients with localized cancers and locally or regionally spread tumours (increase of age-standardized 5-year relative survival from 92% to 98% and from 65% to 80%, respectively, between 1992 and 2008), whereas age-standardized 5-year relative survival essentially remained unchanged at levels close to 21% in patients with metastasized cancer. For women aged 70 years or older 5-year relative survival and its increase over time were inferior compared to younger patients. Conclusions: The observed trends in population based survival suggest that advances in treatment of early breast cancer have substantially contributed to the gain in prognosis. The poor prognosis of metastasized breast cancer patients and the increasing age gradient in 5-year relative survival call for enhanced efforts for early detection and more rigorous treatment of elderly patients.

Green tea consumption, inflammation and the risk of primary hepatocellular carcinoma in a Chinese population - Uncorrected Proof

2011-01-27

Abstract: Objective: Green tea has been found to possess anti-inflammatory, anti-oxidative and anti-carcinogenic properties. The present study examines the association between green tea drinking and hepatocellular carcinoma (HCC) and its interactions with other risk or protective factors and single nucleotide polymorphisms (SNP) of inflammation and oxidative stress related genes. Methods: A population-based case-control study with 204 primary HCC cases and 415 healthy controls was conducted in Taixing, China. Epidemiological data were collected using a standard questionnaire. SNPs of genes of the inflammation and metabolic pathways were genotyped at the UCLA Molecular Epidemiology Laboratory. Logistic regression was performed to estimate adjusted odds ratios and 95% confidence intervals. Results: Longer duration and larger quantities of green tea consumption were inversely associated with primary HCC. Individuals who drank green tea longer than 30 years were at lowest risk (adjusted OR=0.44, 95% CI: 0.19–0.96) compared with non-drinkers. A strong interaction was observed between green tea drinking and alcohol consumption (adjusted OR for interaction=3.40, 95% CI: 1.26–9.16). Green tea drinking was also observed to have a potential effect modification on HBV/HCV infection, smoking and polymorphisms of inflammation related cytokines, especially for IL-10. Conclusion: Green tea consumption may protect against development of primary HCC. Potential effect modifications of green tea on associations between primary HCC and alcohol drinking, HBV/HCV infection, and inflammation-related SNPs were suggested.

A 12-month moderate-intensity exercise intervention does not alter serum prolactin concentrations - Uncorrected Proof

2011-01-27

Abstract: Introduction: Many studies have investigated the immediate impact of physical activity on prolactin concentrations; however, it is currently unclear what impact exercise may have on prolactin concentrations in the long-term, particularly among women. Understanding the role of exercise on prolactin is important because epidemiologic studies have reported increased risks of breast cancer in association with high prolactin concentrations. We investigated whether exercise alters serum prolactin concentrations at two time points within a one-year exercise intervention. Methods: Out of 96 women aged 40–75 years, 47 were randomized to a 12-month regimen of moderate-intensity physical activity and 49 were randomized to the control group. Participants in the exercise group (exercisers) took part in exercise at gym facilities 3 times per week and 3 times per week on their own. Serum prolactin was collected from participants at baseline, 3 and 12 months. Using generalized linear models, we compared the percent change in prolactin concentrations from baseline to the two follow-up time points in the exercisers versus the control group. Results: While we observed the suggestion of differences in the change in serum prolactin concentrations in some subgroups, overall there was no difference in the change in prolactin concentrations between exercisers and controls at 3 months (p=0.84) or 12 months (p=0.19). Conclusion: Our study does not support the hypothesis that long-term exercise influences serum prolactin concentrations.

The association between the survivin −31G/C promoter polymorphism and hepatocellular carcinoma risk in a Turkish population - Uncorrected Proof

Süleyman Bayram, Hikmet Akkız, Aynur Bekar, Ersin Akgöllü — 2011-01-25

Abstract: Background: Survivin, a member of the inhibitor of apoptosis protein family, functions as a key regulator of apoptosis and cell cycle regulation. A common single nucleotide polymorphism (−31G>C) at the survivin promoter has been extensively studied in various cancers and reported to influence survivin expression, but its association with hepatocellular carinoma (HCC) has yet to be investigated. The aim of the present study was to investigate whether this polymorphism could be involved in the risk of HCC susceptibilty. Methods: The genotype frequency of survivin −31G>C polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 160 subjects with HCC and 241 cancer-free control subjects matched on age, gender, smoking and alcohol status. Results: No statistically significant differences were found in the genotype distributions of the survivin −31G>C polymorphism among HCC and cancer-free control subjects (p=0.28). Conclusion: Our results demonstrate for the first time that the survivin −31G/C polymorphism have not been any major role in genetic susceptibilty to hepatocellular carcinogenesis, at least in the population studied here.

Clinical value of 18F-FDG PET/CT in postoperative monitoring for patients with colorectal carcinoma - Uncorrected Proof

Anqin Han, Jie Xue, Dongyuan Zhu, Jinsong Zheng, Jinbo Yue, Jinming Yu — 2011-01-24

Abstract: Objective: To evaluate the clinical value of 18F-FDG PET/CT in postoperative monitoring for patients with colorectal carcinoma. Methods: 66 postoperative patients with colorectal carcinoma underwent whole-body FDG PET/CT. The final histopathological and formal clinical follow-up findings were used as gold standard to determine the sensitivity and specificity of FDG PET/CT and enhanced CT of the same periods. Results: The sensitivity and specificity of FDG PET/CT in detecting recurrence are 96.30%, 94.87% (while enhanced CT are 70.37% and 87.18% respectively). The sensitivity and specificity in detecting metastasis are 95.35%, 82.61% (enhanced CT are 61.90%, 75.00%). SUVmax was significantly higher in malignant lesions [range 4.16–22.00, mean±standard deviation (x±s) 8.06±4.30] than in benign ones (range1.18–6.25, x±s 2.82±1.02). Conclusion: At present, whole-body 18F-FDG PET/CT is an advanced diagnostic imaging technique in detecting loco-regional recurrence and metastasis in postoperative patients with colorectal carcinoma for its higher sensitivity and specificity.

Anthropometric factors and ovarian cancer risk in the Malmö Diet and Cancer Study - Uncorrected Proof

Jenny Brändstedt, Björn Nodin, Jonas Manjer, Karin Jirström — 2011-01-24

Abstract: Objective: To examine the associations of measured anthropometric factors, including general and central adiposity, with epithelial ovarian cancer (EOC) risk in the Malmö Diet and Cancer Study. Methods: In 93 incident EOC cases from a Swedish population-based prospective cohort study, seven anthropometric factors; height, weight, BMI, body fat percentage, waist- and hip circumference, and waist-hip ratio (WHR), were categorized by tertiles of baseline anthropometric measurements and relative risks were calculated using multivariate Cox regression models. Results: A high WHR (<0.77, ≥0.77 to <0.81, ≥0.81cm/cm) was associated with a statistically significantly lower overall risk for EOC (RR 0.60; 0.36–1.00; p-trend=0.04), particularly tumours of differentiation grades 1 and 2 (RR 0.27; 0.09–0.81; p-trend=0.03) and clinical stages 1 and 2 (RR 0.32; 0.10–0.97; p-trend=0.03) and these associations were stronger in postmenopausal women. Neither height, weight, BMI, body fat percentage, waist- or hip circumference were associated with overall risk, nor with risk for different subtypes, differentiation grade or stage. Conclusions: These results demonstrate that a high WHR is associated with a decreased risk of EOC. Other anthropometric factors were not associated with EOC risk.

Hidden malignant cells within leukocyte aggregates: Seeds for invasive and metastatic cancer? - Uncorrected Proof

Yi-Hsuan Hsiao, Chuxia Deng, Jeffrey T. Mason, Ming-Chih Chou, Yan-gao Man — 2011-01-18

Abstract: Background: Our previous studies revealed that leukocyte infiltration into aged or injured myoepithelial cell layers is a key trigger for breast tumor invasion and metastasis. Our current study further assessed the possibility that leukocyte aggregates may harbor detached individual tumor cell or clusters of tumor cells. Materials and methods: Tissue sections from patients with pregnancy-associated breast cancer (PABC) and controls were subjected to morphological and immunohistochemical assessment with a panel of leukocyte and tumor cell related markers. Results: A total of 63 leukocyte aggregates were detected in the 20 PABC cases studied. Of these, 55 (87%) were distributed within normal or hyperplastic lobules adjacent to invasive lesions. Over 70% of these leukocyte aggregates harbored detached individual tumor cell or cell clusters with malignant properties, including strong p53 positivity, elevated proliferation, reduced cell surface adhesion molecules, and cytological resemblance to adjacent invasive cancer cells. A significant number of these tumor cells or condensed chromosomes of mitotic tumor cells were observed to conjoin with the plasma membrane of leukocytes. Similar alterations were seen in leukocyte aggregates within the inter-lobular space and in non-PABC with a lower frequency. Conclusions: These findings suggest that leukocyte infiltration may trigger dissemination of tumor cells from their primary site, and that leukocyte aggregates may serve as a reservoir for disseminated tumor cells that may be physically dragged to distant sites by leukocytes during their migration.

Human papillomavirus infection in women with and without cervical cancer in Tbilisi, Georgia - Uncorrected Proof

2011-01-06

Abstract: Background: No accurate estimates of cervical cancer incidence or mortality currently exist in Georgia. Nor are there any data on the population-based prevalence of high-risk (HR) human papillomavirus (HPV) infection, which, in the absence of good-quality screening, is known to correlate with cervical cancer incidence. Methods: We obtained cervical cell specimens from 1309 women aged 18–59 years from the general population of Tbilisi, and also from 91 locally diagnosed invasive cervical cancers (ICC). DNA of 44 HPV type was tested for using a GP5+/6+-based PCR assay. Results: In the general population (of whom 2% reported a previous Pap smear) HPV prevalence was 13.5% (95% CI: 11.6–15.9), being highest in women aged 25–34 years (18.7%) and falling to between 8.6% and 9.5% for all age groups above 34 years. HR HPV prevalence was 8.6% overall, being 6.8% and 38.9% among women with normal and abnormal cytology, respectively. HPV45 (1.6%) was the most common type in women with normal cytology, whereas HPV16 predominated among women with cervical abnormalities (including 7 of 10 histologically confirmed cervical intraepithelial neoplasia 2/3) and among ICC (57.6%). The next most common types in ICC in Georgia were HPV45 and 18 (13.2 and 11.0%, respectively). Conclusions: We report a relatively high burden of HPV infection in Tbilisi, Georgia. Improving cervical cancer prevention, through screening and/or HPV vaccination, is an important public health issue in Georgia, where 70% of ICC are theoretically preventable by HPV16/18 vaccines.

CD40 is overexpressed by HPV16/18-E6 positive cervical carcinoma and correlated with clinical parameters and vascular density - Uncorrected Proof

2011-01-03

Abstract: CD40 is expressed in many tumor cells, however, its role in tumor biology is yet to be demonstrated. In the present study, we investigated the role of CD40 in cervical carcinoma. In vivo, we evaluated CD40 expression in 56 cervical carcinoma tissues, 43 cervicitis and 38 normal cervix, and investigated the relationship between CD40 and HPV antigen, histopathological parameters, vascular density, and vascular endothelial growth factor (VEGF) expressions. The results clearly demonstrated that CD40 expression, including membranous and cytoplasmic staining, was significantly higher in cervical carcinoma than in the cervicitis and normal cervix. The expression of CD40 was significantly correlated with HPV and VEGF expressions and microvessel density (MVD). These observations provide evidence that CD40 may be involved in neovascularization of cervical carcinoma, they also suggest that CD40 and VEGF may be useful biomarkers for evaluating the risk of developing cervical carcinoma, and may also be used as a target for therapy.

Mammographic density and hormone receptor expression in breast cancer: The Multiethnic Cohort Study - Uncorrected Proof

Shannon M. Conroy, Ian Pagano, Laurence N. Kolonel, Gertraud Maskarinec — 2011-01-03

Abstract: Background: It is unclear whether mammographic breast density, a strong risk factor for breast cancer, predicts subtypes of breast cancer defined by estrogen receptor (ER) and/or progesterone receptor (PR) expression. Methods: In a nested case–control study, we compared the breast density of 667 controls and 607 breast cancer cases among women of Caucasian, Japanese, and Native Hawaiian ancestry in the Hawaii component of the Multiethnic Cohort Study. A reader blinded to disease status performed computer assisted density assessment on prediagnostic mammograms. Receptor status was obtained from the statewide Hawaii Tumor Registry. Tumors were classified into ER+PR+ (n=341), ER−PR− (n=50), ER+PR−/ER−PR+ (n=64), and unstaged/unknown (n=152). Mean density values were computed for women with more than one mammogram. Polytomous logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) while adjusting for confounders. Results: Mean density was significantly greater for ER+PR+ but not for ER−PR− tumors compared to controls after adjusting for age: 37.3%, 28.9% versus 29.4%, respectively. The overall OR per 10% increase in density were similar for ER+PR+ and ER+PR−/ER−PR+ tumors: 1.26 (95% CI 1.17–1.36) and 1.23 (95% CI 1.07–1.42), respectively. However, percent density was not found to be a predictor for ER−PR− tumors (OR 1.00, 95% CI 0.84–1.18). The results did not differ by ethnicity, nor by menopausal status, parity, or HRT use. Conclusions: Our findings indicate that within a multiethnic population, women with higher breast density have an increased risk for ER+PR+ but not ER−PR− tumors.

Socioeconomic position and lifestyle in relation to breast cancer incidence among postmenopausal women: A prospective cohort study, Denmark, 1993–2006 - Uncorrected Proof

2011-01-03

Abstract: Background: In Denmark, the incidence of breast cancer is higher among women with higher socioeconomic position. We investigated whether differences in exposure to certain risk factors contribute to this gradient, as measured from education, income and occupation. Methods: We conducted a cohort study of 23111 postmenopausal women aged 50–65 years who were enrolled in the prospective Danish ‘Diet, Cancer and Health’ study between 1993 and 1995. At baseline, all women filled in a questionnaire on lifestyle and food frequency. The results were analysed in Cox proportional hazard models. Results: Part of the association with socioeconomic position is due to the potential mediators reproductive pattern, use of hormone replacement therapy and alcohol consumption. After simultaneous adjustment for these factors, the hazard ratios were 1.06 (95% confidence interval [CI], 0.88–1.27) for women with higher education and 1.07 (95% CI, 0.85–1.34) for women with higher income. The HR ratio for women working as higher officials when compared with unskilled workers was 1.23 (0.96–1.59). Conclusion: The results support the hypothesis that the higher incidence of breast cancer among socially advantaged women is mediated partly by differences in exposure to reproductive factors, hormone replacement therapy and alcohol.

Validity of self-reported cancer among a Japanese population: Recent results from a population-based prospective study in Japan (JPHC Study) - Uncorrected Proof

2010-12-23

Abstract: The recent tendency of Japanese towards greater acceptance of being informed that they have cancer, along with the growing understanding and use of informed consent, appears to have improved the accuracy of self-reported cancer. To clarify the recent validity of self-reports, we measured the sensitivity and positive predictive value of self-reported cancer among a Japanese population. Using a 10-year follow-up questionnaire conducted in 2000–2004 and the cancer registry of the JPHC Study cohort (n=93,680), we calculated the sensitivity and positive predictive value of self-reported cancer diagnoses over 10 years. Sensitivity and positive predictive value of total self-reported cancer diagnoses were 53% and 60%, respectively, but varied by site, at 62% and 52% for stomach, 38% and 47% for colorectum, 57% and 46% for lung, 34% and 31% for liver, 82% and 58% for breast, and 59% and 22% for uterus, respectively. Sensitivity was considerably improved from that in the previous report (36%), which tested for 1990–1995, but was still not considered satisfactory. Self-reported diagnoses of cancer do not provide sufficient accuracy for the detection and classification of incident cancers. Our findings may be extrapolated to other Japanese populations.

Balancing sensitivity and specificity: Sixteen year's of experience from the mammography screening programme in Copenhagen, Denmark - Uncorrected Proof

Nicolai Utzon-Frank, Ilse Vejborg, My von Euler-Chelpin, Elsebeth Lynge — 2010-12-22

Abstract: Aim: To report on sensitivity and specificity from 7 invitation rounds of the organised, population-based mammography screening programme started in Copenhagen, Denmark, in 1991, and offered biennially to women aged 50–69. Changes over time were related to organisation and technology. Methods: Individualized data were retrieved on outcome of screening mammography, assessment, surgery, and interval cancers. European Guideline performance indicators were calculated, supplemented with false positive and interval cancer rates per 1000 screens. False positive tests were divided into those sorted out at assessment (Type 1) and at surgery (Type 2). Results: In total, 1392 invasive breast cancers/ductal carcinoma in situ cases (DCIS) were diagnosed, giving an overall detection rate of 7.6 per 1000 screens. Of 5178 false positive tests, 4666 were Type 1 and 512 Type 2. The 468 interval cancers constituted 25% of all breast cancers (=screen detected+interval cancer). Almost all outcome measures were well within the desirable level of the European Guidelines. Risk of Type 2 false positive tests was positively associated with detection rate especially at initial screen, and interval cancer rate was negatively associated with detection rate. This association was decoupled after introduction of high resolution ultrasound and stereotactic breast biopsies, resulting in a Benign-to-Malignant-Ratio (BMR) of 1:11.40. Conclusion: Mammography screening is a delicate balance between benefits and risks. Increase in detection rate came at cost of increase in risk of benign biopsies. Introduction of new technologies broke this pattern and a slight increase in detection rate coincided with an unprecedentedly low BMR.

CYP17 gene polymorphism and prostate cancer susceptibility in a Tunisian population - Uncorrected Proof

Yousra Souiden, Manel Mahdouani, Kamel Chaieb, Rafik Elkamel, Kacem Mahdouani — 2010-12-16

Abstract: Prostate cancer (PCa) formation has been reported to be associated with androgen. Two key steps in the sex steroid synthesis are mediated by the enzyme cytochrome P450c 17α which is encoded in the CYP17 gene. The A2 allele of the CYP17 gene has been thought to be associated with increased functional activity of this steroidogenic enzyme. Consequently, the A2 allele has been examined as a biomarker of individual susceptibility to hormone-related diseases among men. We prospectively assessed the association between the A2 allele of CYP17 and PCa risk among 125 cases and 125 controls in a case–control study. Our aim was to investigate whether a polymorphism of CYP17 gene could be used as a genetic marker for associating PCa. The result revealed a significant association between the CYP17 polymorphic genotypes and PCa. Therefore, CYP17 gene polymorphism is likely contributed to the pathogenesis of PCa but not to disease severity.

Cytogenetic and comparative genomic hybridization study of Indian myelodysplastic syndrome - Uncorrected Proof

Nikesh Kawankar, Farah Jijina, Kanjaksha Ghosh, Babu Rao Vundinti — 2010-12-15

Abstract: Introduction: Myelodysplastic syndromes (MDSs) are clonal stem cell disorders characterized by cytopenias, dysplasia in one or more cell lineages and ineffective hematopoiesis and are associated with significant morbidity and mortality due to bone marrow failure or evolution to acute myeloid leukemia. Clonal chromosomal abnormalities are detected in 40–60% of patients. Multiple recurrent chromosomal aberrations have been identified by cytogenetics including fluorescence in situ hybridization (FISH) which is now widely recognized as one of the most important diagnostic and prognostic markers in MDS. Methods: Conventional cytogenetics by GTG-banding, FISH, comparative genomic hybridization (CGH) was done on 40 primary MDS subjects. Results: Among 40 subjects, 10 (25%) were abnormal and 30 (75%) showed apparently normal karyotypes with GTG banding and FISH. The various aberrations observed were del 5q−, del 7q−, 20q−, +8. DNA copy number changes including losses (30%) and gains (20%) were detected by CGH in 11 (36.6%) out of 30 karyotypically normal MDS. However chromosome 7 (37%) and 1 (25%) is frequently involved in current study population. Conclusions: This study confirms that the apart from non-random chromosome aberrations, other chromosome regions also involved in the MDS development. The occupational, environmental and geographical variations might be influencing the disease. Furthermore cytogenetic studies are warranted in larger groups of MDS cases to identify newly acquired chromosome aberrations that may aid in cloning new genes involved in the neoplastic process, ultimately helping in the development of targeted therapeutic drugs.

Global prostate cancer incidence and the migration, settlement, and admixture history of the Northern Europeans - Uncorrected Proof

Kristin Gunderson, Christopher Y. Wang, Ruoxiang Wang — 2010-12-09

Abstract: The most salient feature of prostate cancer is its striking ethnic disparity. High incidences of the disease are documented in two ethnic groups: descendents of the Northern Europeans and African Americans. Other groups, including native Africans, are much less susceptible to the disease. Given that many risk factors may contribute to carcinogenesis, an etiological cause for the ethnic disparity remains to be defined. By analyzing the global prostate cancer incidence data, we found that distribution of prostate cancer incidence coincides with the migration and settlement history of Northern Europeans. The incidences in other ethnic groups correlate to the settlement history and extent of admixture of the Europeans. This study suggests that prostate cancer has been spread by the transmission of a genetic susceptibility that resides in the Northern European genome.

Population attributable risk of invasive postmenopausal breast cancer and breast cancer subtypes for modifiable and non-modifiable risk factors - Uncorrected Proof

2010-12-03

Abstract: Background: The population-level impact of modifiable postmenopausal breast cancer risk factors is incompletely understood, especially regarding potential heterogeneity by estrogen receptor (ER) and progesterone receptor (PR) status.Methods: Using data on 3074 cases and 6386 controls from a population-based case–control study of postmenopausal breast cancer conducted in Germany between 2002 and 2005, we calculated multivariable-adjusted odds ratios and population attributable risks (PARs) for modifiable and non-modifiable risk factors. We examined overall postmenopausal invasive breast cancer as well as tumor ER/PR subtypes. A bootstrap method provided estimates of 95% confidence intervals (95%CIs).Results: The summary PARs (95%CIs) for non-modifiable risk factors (age at menarche, age at menopause, parity, benign breast disease, and family history of breast cancer) were 37.2% (27.1–47.2%) regarding overall invasive tumors, 36.5% (23.3–47.6%) regarding ER+/PR+ tumors, 47.9% (26.4–64.4%) regarding ER+/PR− tumors, and 31.1% (4.0–51.9%) regarding ER−/PR− tumors. Of the modifiable risk factors (hormone therapy (HT) use, physical inactivity, BMI, alcohol consumption), HT use and physical inactivity had the highest impact with PARs of 19.4% (15.9–23.2%) and 12.8% (5.5–20.8%), respectively, regarding overall invasive tumors. For ER+/PR+ tumors, the corresponding PARs were 25.3% (20.9–29.7%) and 16.6% (7.0–26.0%). The summary PARs (95%CIs) for HT use and physical inactivity together were 29.8% (21.8–36.9%) and 37.9% (30.6–46.2%) regarding overall invasive and ER+/PR+ tumors, respectively.Conclusions: The population-level impact of modifiable risk factors appears to be comparable to that of non-modifiable risk factors. Alterations in HT use and physical inactivity could potentially reduce postmenopausal invasive breast cancer incidence in Germany by nearly 30%, with the largest potential for reduction among ER+/PR+ tumors, the most frequently diagnosed subtype.

Minimal detection bias in the inverse association between statin drug use and advanced prostate cancer risk: A simulation study - Uncorrected Proof

Alison M. Mondul, Brian Caffo, Elizabeth A. Platz — 2010-12-03

Abstract: Background: Prospective studies support that statins may protect against advanced prostate cancer. Detection bias arising from higher PSA screening rates among statin users vs. non-users could produce an inverse association for advanced disease. Thus, we conducted simulations to assess whether this source of bias is explanatory. Methods: 3000 datasets with 100,000 men without prostate cancer were simulated for populations with high (65%) or low (15%) PSA screening. We investigated three scenarios: RRtrue=1.0, 0.75, and 0.5 for statins and advanced disease (1.0 for localized). We set the statin prevalence to 10% and varied the percentage of users who were PSA screened (0–100%). We assumed an annual total prostate cancer incidence of 1%, with risk in screened men twice that of unscreened men, and an advanced stage at diagnosis in 20% and 40% of cases in screened and unscreened men, respectively. Results: As PSA screening and statin use became more coincident, the RRobserved for local and total prostate cancer was biased upward from the RRtrue of 1.0, especially when the prevalence of PSA screening was low. However, in all simulated scenarios, there was little downward bias for advanced disease (e.g., if RRtrue=1.0 and 70% of statin users and either 65% or 15% of the population overall was PSA screened, then RRobserved=0.98 for both). Conclusions: Given our assumptions, this simulation suggests that this source of detection bias is unlikely to explain the reported inverse association between statins and advanced prostate cancer, but may explain the positive association for total prostate cancer that has been reported in some studies.

Cyclin D1 gene polymorphism, A870G, is associated with an increased risk of salivary gland tumors in the Chinese population - Uncorrected Proof

Weijia Liu, Enxin Zhu, Ru Wang, Lihong Wang, Lu Gao, Xuesong Yang, Tingjiao Liu — 2010-12-02

Abstract: Expression of Cyclin D1 is believed to lead to progression through the G1 to S cell cycle checkpoint, and both experimental and pathological evidence suggests that overexpression of this protein may increase the risk of several cancers. The Cyclin D1 A870G polymorphism may modulate expression of the Cyclin D1 protein and is associated with the development of several types of tumor. We investigated the association between the Cyclin D1 A870G polymorphism and susceptibility to salivary gland tumors (SGTs) by PCR-RFLP in 102 Chinese SGT patients and 101 healthy controls. The frequencies of the AG (p=0.002; odds ratio (OR), 3.466) and AA (p=0.003; OR, 3.133) genotypes of Cyclin D1 were significantly higher in patients with SGT than in the healthy controls. The frequencies of these two genotypes were also significantly higher in pleomorphic adenoma (PA) patients (p=0.002; OR, 2.229), compared with the healthy controls. In addition, the expression of Cyclin D1 was found to be significantly higher in PA patients with the AA genotype, compared with PA patients with the GG genotype. Taken together, our results suggested that the Cyclin D1 A870G polymorphism is associated with an increased risk of SGTs in the Chinese population. The Cyclin D1 AA genotype not only increased the risk of PA, but also increased the expression of Cyclin D1 in this type of tumor.