Cancer Epidemiology

Editorial Board

2010-08-01

Regional trends in prostate cancer incidence, treatment with curative intent and mortality in Norway 1980–2007

2010-05-14

Abstract: Objectives: To compare the trends in prostate cancer incidence, treatment with curative intent and mortality across regions and counties in Norway, and to consider changes in incidence (an indicator for early diagnosis) and treatment with curative intent as explanatory factors for the decreasing prostate cancer mortality rates. Patients and methods: Prostate cancer incidence and mortality data (1980–2007) alongside treatment data (1987–2005) were obtained from the national, population-based Cancer Registry of Norway. Joinpoint regression models were fitted to age-adjusted incidence, treatment and mortality rates to identify linear changes in the trends. Results: Both age-adjusted incidence rates and rates of curative treatment of prostate cancer increased significantly in all five regions of Norway since the early 1990s. There was a strong positive correlation between increasing incidence and increasing use of curative treatment. The frequency of curative treatment in Western Norway was almost threefold that in the Northern and Central regions around year 2000. Subsequently, the regional trends converged and only minor differences in prostate cancer incidence and use of curative treatment were observed by 2005. The declines in mortality were observed earliest in the regions with the highest incidence and the most frequent use of curative treatment, while the largest decreases in mortality were found in counties where the largest increases in curative treatment were observed. Conclusions: The elucidation of the prostate cancer mortality trends is hindered by an inability to tease out the potential effects of early treatment from the more general impact of improved and more active treatment. However, it is likely that both sets of intervention have contributed to the decline in prostate cancer mortality in Norway since 1996.

Years of potential life lost caused by prostate cancer deaths in the United States—Projection from 2004 through 2050

Chunyu Li, Donatus U. Ekwueme — 2010-05-07

Abstract: Background: The purpose of this study is to estimate and project the number of years of potential life lost (YPLL) among males who die of prostate cancer in the United States from 2004 through 2050 and compare the projections by race/ethnicity and age, accounting for demographic changes and population growth.Methods: We applied the life expectancy method to estimate YPLL caused by deaths of prostate cancer and all cancers in men by using 1999–2004 national mortality data, 2008 census population demographic projections, and 2004 U.S. life tables. We performed sensitivity analyses by varying death rate and population projections, and examined increase in YPLL from population growth, changes in demographics, and death rates.Results: The number of YPLL caused by prostate cancer deaths was projected to increase by 226.1%, from 291,853 in 2004 to 951,753 in 2050. Hispanics were projected to have the fastest growth in YPLL (977.1% from 2004 to 2050) caused by prostate cancer, followed by non-Hispanic blacks (543.1%), and non-Hispanic others (269.7%). People aged 75 or older was projected to account for 62.0% of YPLL from prostate cancer in 2050 compared with 50.8% in 2004. Of the projected increase in YPLL caused by prostate cancer deaths by 2050, 9.8% were due to changes in demographic composition, 26.8% because of mortality change, and 63.4% because of population growth.Conclusions: YPLL due to prostate cancer deaths are projected to increase dramatically, and become a greater burden in the future. The projections highlight the importance of comprehensive cancer control and research on cancers including prostate cancer and racial/ethnic-specific estimates.

Geographical analysis of cancer incidence in Ireland: A comparison of two Bayesian spatial models

Avril C. Hegarty, Anne-Elie Carsin, Harry Comber — 2010-05-14

Abstract: Aims: Our objective was to describe the geographical variation in cancer incidence using gastro-intestinal and non-melanoma skin cancer incidence data in Ireland using two different Bayesian spatial models and to compare the performance of these models. Methods: Cases diagnosed between 1994 and 2003 were extracted from the National Cancer Registry of Ireland. Population data were estimated from census data. For each of 3401 electoral divisions (EDs), relative risk (RR) estimates were calculated and smoothed using a conditional autoregressive model (CAR) and a spatial partition model introduced by Hegarty and Barry using a product partition model (PPM). The results were compared by mapping the ratio of the two RR estimates and other mainly descriptive statistics. Results: The two methods gave broadly similar results. For gastro-intestinal cancers the RRs were lower in a northwest/southeast band across the country with greater RRs around Dublin, Cork and in Donegal. Greater RR of non-melanoma skin cancer was observed in coastal areas. Median differences between the RR estimates were small (=0.01). The range of RRs was wider when estimated by the CAR model illustrating that the PPM smoothed the data to a greater extent than the CAR model. Conclusions: The two approaches gave similar results providing stronger evidence for the resulting geographical patterns. PPMs give a more global picture of the risk distribution whereas CAR models provide more local estimates. The observed patterns may reflect socio-demographic or geographic variations in risk factors or access to cancer services. By helping to identify those risks, these maps may help in the optimal allocation of scarce health resources.

The validity and reliability of the Socioeconomic Status Instrument for assessing prostate cancer patients

Mfon Cyrus-David — 2010-05-18

Abstract: Background: Because of the lack of consistency in the associations of the socioeconomic status (SES) of prostate cancer (PC) patients from diverse racial and ethnic backgrounds with PC health outcomes, I created the Socioeconomic Status Instrument (SESI) from the Demographic and Health Access components of the Behavioral Risk Factor Surveillance System 2004 Questionnaires and the socioeconomic indices of the subjects’ residential counties to better assess the SES of PC patients. Methods: The SESI was tested on 220 consecutive subjects with pathologically confirmed PC at the Veterans Affairs Medical Center in Houston, TX. A team that included an epidemiologist, a validation statistician/health services research scientist, and PC survivors assessed the content validity of the SESI. The construct validity of the SESI was assessed with factor analysis by extracting and analyzing 5 principal components based on the subjects’ individual responses on the assessment: county socioeconomic characteristics, individual socioeconomic characteristics, financial distress, increased domestic burden with limited earnings, and affluence. The internal consistency reliability of the SESI was assessed with Cronbach's alpha coefficients. Results: Based on the reviews of the SESI, all of the initial 10 items were retained. The correlations between individual responses on the SESI were similar to the results of previous studies. The 5 principal components that I assessed accounted for 71.5% of the variance. Factor loadings ranged from 0.66 to 0.98 and communalities ranged from 0.55 to 0.94. County socioeconomic characteristics accounted for 22.6% of the variance, whereas individual socioeconomic characteristics accounted for 14.6% of the variance. The overall Cronbach's alpha coefficient was 0.78. Conclusions: The SESI is valid and reliable. Accurate measurements of the SES of PC patients would provide better guidance for future research and care deliveries.

Occupational exposure to hexavalent chromium and cancers of the gastrointestinal tract: A meta-analysis

Nicole M. Gatto, Michael A. Kelsh, Diem Ha Mai, Mina Suh, Deborah M. Proctor — 2010-04-08

Abstract: Introduction: We conducted a systematic literature review and meta-analysis of oral cavity, esophageal, stomach, small intestine, colon, and rectal cancers among workers occupationally exposed to Cr(VI). Methods: Using PubMed, studies published from 1950 to 2009 evaluating the relationship between Cr(VI) exposure and GI cancers were identified. Measures of effect and variability were extracted from 32 studies meeting specific inclusion criteria, and meta-analysis summary relative risk measures were calculated using random effects models and inverse variance weighting methods. Results: Meta-standardized mortality ratios (SMRs) were, for cancer of the: oral cavity [1.02 (95% CI=0.77–1.34)]; esophagus [1.17 (95% CI=0.90–1.51)]; stomach [1.09 (95% CI=0.93–1.28)]; colon [0.89 (95% CI=0.70–1.12)]; and rectum [1.17 (95% CI=0.98–1.39)]. Analyses of more highly exposed subgroups included in the studies or subgroups based on geographic region or by industry with recognized Cr(VI) exposures (welding, chrome plating, chromate production, and pigment production) did not result in elevated meta-SMRs except for esophageal cancer among US cohorts [meta-SMR=1.49 (95% CI=1.06–2.09)]. However, that finding was based on a subgroup of only four studies, one of which was a PMR study. Potential confounding by socioeconomic status (SES), diet and/or smoking, or limitations due to the healthy-worker effect (HWE) were evaluated, and while smoking, diet and SES may be important factors that may have upwardly biased the meta-SMRs, HWE is not likely to have significantly affected the summary results. None of three studies reporting small intestine cancers observed a statistically significant increased risk. Discussion: These meta-analyses and literature review indicate that Cr(VI)-exposed workers are not at a greater risk of GI cancers than the general population.

Prenatal exposure to medicines and the risk of childhood brain tumor

Karin Stålberg, Bengt Haglund, Bo Strömberg, Helle Kieler — 2010-05-13

Abstract: Background: Childhood brain tumors are associated with high mortality and morbidity but little is known about its causes. About half of women use medicines when pregnant and some of the medicines commonly used might be carcinogenic. Objective: The aim with this population-based case–control study was to analyze associations between specific groups of medicines taken during pregnancy and the risk of brain tumor in the offspring. Methods: All children, up to 15 years of age, born in Sweden between 1975 and 1984 were eligible for the study. Cases (N=512) were children diagnosed with brain tumor and controls (N=525) were randomly selected from the Medical Birth Register. Exposure data on medicines was extracted blindly from antenatal medical records and grouped according to Anatomical Therapeutic Chemical (ATC) code. Information on maternal reproductive history was received from the Medical Birth Register. We used logistic regression to estimate associations between fetal exposure to medicines and childhood brain tumor. Results: No significant changes in risk were noted after exposure to iron supplementation, antiemetics, analgesics, antibiotics or any other main ATC group. A tendency of protective effect was seen for prenatal exposure to folic acid (adjusted OR 0.6, 95% CI 0.3–1.1). Ten children with a diagnosis of brain tumor had been exposed to β-blocking agents in fetal life as compared to two children without brain tumor (adjusted OR 5.3, 95% CI 1.2–24.8). Conclusions: In this case–control study, an increased risk of brain tumor was seen in children exposed to β-blocking agents during fetal life. However, due to the low number of exposed the interpretation of this finding should be made with caution.

Effect of tobacco chewing, tobacco smoking and alcohol on all-cause and cancer mortality: A cohort study from Trivandrum, India

2010-04-26

Abstract: Objective: To study the risk of all-cause, cancer and tobacco-related cancer mortality associated with tobacco chewing, tobacco smoking and alcohol use. Design: Prospective community-based cohort study initiated in 1996. Participants: 167343 adult subjects, aged 34 and older, living in 13 panchayaths (rural municipal administrative units) in South India, were regularly followed-up for a mean duration of 6.5 years. Main outcome measures: Mortality from all-causes, all cancer and tobacco-related cancer. Results: The mortality risks associated with chewing (and 95% confidence intervals), after adjusting for age, sex, socio-economic and dietary variables, and for other habits, were 0.90 (0.86–0.94) for all-cause, 1.07 (0.94–1.22) for cancer and 1.22 (1.04–1.44) for tobacco-related cancer; with smoking the respective mortality risks were 1.31 (1.24–1.39), 1.63 (1.37–1.94) and 1.68 (1.36–2.08); and with alcohol use the risks were 1.13 (1.06–1.20), 1.32 (1.11–1.57) and 1.47 (1.19–1.80), respectively. Reduced risk of all-cause mortality by chewing was observed only in the 60–84 years old group (0.90 (0.85–0.94)), and detrimental effects of chewing on cancer mortality were shown in the young and middle-age groups: 34–39 years old (1.33 (0.67–2.65)), and 40–59 years old (1.26 (1.03–1.55)). Conclusion: Tobacco in any form and alcohol uses were harmful and a higher quality of life could be achieved by avoiding these habits. Given the demographic, epidemiological and economic transitions and changes in pattern of tobacco and alcohol use in India, the health loss from the tobacco and alcohol will grow even larger, unless effective interventions and policies to reduce these habits are implemented.

Does consanguinity lead to decreased incidence of breast cancer?

2010-04-26

Abstract: Background: In the Middle East region, consanguinity remains to be a central feature where it has shown an increasing trend. Breast cancer is an extremely complex disease, characterized by a progressive multistep process caused by interactions of both environmental and genetic factors. Aim: The aim of this study was to examine the possible effect of consanguinity on the risk of breast cancer in a population with a high rate of consanguinity and find the associated risk-modifying factors. Subjects and methods: The study included 167 Qatari and other Arab expatriates women with breast cancer and 341 age and ethnicity matched control women. A questionnaire that included the socio-demographic information, type of consanguinity, medical history, life style habits, dietary intake and tumor grade was designed to collect, the information of cases and controls. A total number of 214 breast cancer patients were approached and 167 cases completed the questionnaires with a response rate of 78%. Of the 417 healthy women who agreed to participate in this study, 341 responded to the questionnaire (81.8%). Results: The study revealed that the rate of parental consanguinity was lower in breast cancer patients (24%) than in controls (32.3%) (p=0.062). Female controls were slightly younger (46.5±11.9) than breast cancer patients (48.4±10.7). Breast cancer incidence was significantly higher in Qatari women (34.1%) compared to other Arab women (65.9%) (p=0.034). A significant difference was noted only in occupation of the studied women between cases and controls (p<0.001). Overweight (46.7%) and obesity (32.9%) were significantly higher in female breast cancer patients compared to controls (p=0.028). Overall, the mean coefficient of consanguinity was lower in breast cancer patients (0.014) than in controls (0.018) (p=0.0125). Family history of breast cancer was significantly more often in breast cancer patients (14.4%) than in controls (6.2%) (p=0.002). However, the family history of breast cancer was more often positive in cases of non-consanguineous parents (15.7%) than cases of consanguineous parents (10.0%). Conclusion: The present study revealed the lack of association between of breast cancer and the parental consanguinity in Arab women residing in Qatar. The family history of breast cancer and the body mass index (BMI) are highly associated with breast cancer.

Effect of family history of cancers and environmental factors on risk of nasopharyngeal carcinoma in Guangdong, China

2010-04-30

Abstract: Background: Family history of nasopharyngeal carcinoma (NPC) is an established risk factor for this cancer, but the contributions of family history of other types of cancer and its interaction with environmental factors have not been well characterized. Methods: A total of 1845 incident cases of NPC and 2275 matched controls from Guangdong, China were included in this study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from logistic regression models adjusted for smoking, consumption of alcohol, salted fish consumption, and demographic factors. Results: A significant association between the risk of NPC and family history of any cancers in first degree relatives was observed, and higher number of affected family member was related to a higher risk (Ptrend<0.01). Family history of NPC was the strongest predictor for NPC (OR: 3.35, 95% CI: 2.46–4.55 for all first degree relatives). The risk of NPC was also positively associated with history of head and neck cancer among parents and lung and breast cancers among siblings. The combination of family history of cancer, especially NPC, and the consumption of salt-preserved fish significantly increased the risk for NPC. Conclusions: These results confirm that the risk for NPC increases with family history of NPC and suggest that lung and breast cancer contribute to risk for NPC. A possible interaction between family history of cancer, especially NPC, and consumption of salt-preserved fish in the development of NPC was also identified.

Assessment of women's risk factors for breast cancer and predictors of the practice of breast examination in two rural areas near Ibadan, Nigeria

O. Abimbola Oluwatosin — 2010-04-26

Abstract: Objective: In Nigeria, breast cancer is the most common cancer among women in majority of the regions. Late presentation has also been reported for about four decades. This study assessed the women's risk factors for breast cancer and predictive factors for the practice of breast examinations. The findings will be of help in enhancing early detection of the disease and reducing mortality from the disease. Methods: Utilizing a multi-stage sampling method, 420 women were selected at Akinyele Local government area of Ibadan. Data was collected with questionnaire. The risk factor was evaluated using the breast cancer risk assessment tool based on the Gail model. Six demographic factors, plus four covariates: knowledge of BSE/CBE, knowledge of the cause of, symptoms and signs of and treatment of breast cancer, were regressed against two dependent variables of practice of BSE and CBE using linear regression and binary logistic analyses respectively. Results: Only 386 questionnaires properly filled were analyzed. The mean age of respondents was 37.3 (SD=13.1) years. They were of low educational status and were mostly traders and married. Only 190 of the women fulfilled the criteria for assessment with the Gail model. Most of the women, 180 (94.7%), had five years and 184 (96.8%) had lifetime risks lower than that of the average woman of the same age. Four significant predictors of BSE were marital status (p=0.004), educational status (p=0.018), knowledge of treatment of breast cancer (p=0.029) and knowledge of BSE/CBE (p=0.0001) while no formal education status and being a farmer were the only significant predictors of CBE. Conclusions: The findings are useful for planning interventional studies to enhance early detection in a low resource country.

Estimating key parameters in periodic breast cancer screening—Application to the Canadian National Breast Screening Study data

Yinlu Chen, Guy Brock, Dongfeng Wu — 2010-04-21

Abstract: Problem statement: Breast cancer screening in women of younger age has been controversial. The screening sensitivities, transition probabilities and sojourn time distributions are estimated for females aged 40–49 years and 50–59 years separately, using the Canadian National Breast Screening Study (CNBSS) data. The purpose is to estimate the lead time distribution and the probability of not detecting the cancer early. Approach: Within the 40–49-year-old and 50–59-year-old cohorts separately, the age-independent statistical model was applied. Bayesian estimators along with 95% highest probability density (HPD) credible intervals (CI) were calculated. Bayesian hypothesis testing was used to compare the parameter estimates of the two cohorts. The lead time density was also estimated for both the 40–49 and 50–59-year-old cohorts. Results: The screening sensitivity, transition probability of the disease, and mean sojourn time were all found to increase with age. For the 40–49-year-old and 50–59-year-old cohorts, the posterior mean sensitivities were 0.70 (95% HPD-CI: 0.46, 0.93) and 0.77 (0.61, 0.93), respectively. The posterior mean transition probabilities were 0.0023 (0.0018, 0.0027) and 0.0031 (0.0024, 0.0038), while the posterior mean sojourn times were 2.55 (1.56, 4.26) years and 3.15 (2.12, 4.96) years. Bayes factors for the ratio of posterior probabilities that the respective parameter was larger vs. smaller in the 50–59-year-old cohort were estimated to be 2.09, 40.8 and 3.0 for the sensitivity, transition probability, and mean sojourn time, respectively. All three Bayes factors were larger than two, indicating greater than 2:1 odds in favor of the hypothesis that each of these parameters was greater in the 50–59-year-old cohort. The estimated mean lead times were 0.83 years and 0.96 years if the two cohorts were screened annually. Conclusions: The increase in sensitivity corresponds to an increase in the mean sojourn time. Breast cancer in younger women is more difficult to detect by screening tests and is more aggressive than breast cancer in older women. Women aged 50–59 tend to benefit more from screening compared with women aged 40–49.

Print news coverage of cancer: What prevention messages are conveyed when screening is newsworthy?

Katherine Clegg Smith, Elizabeth Edsall Kromm, Ann Carroll Klassen — 2010-03-02

Abstract: Background: Americans are generally favorable towards cancer screening, but fatalistic about cancer prevention. News coverage shapes perceptions of cancer control in meaningful ways, but there is little consensus as to the impact of news on our understanding of and engagement in cancer screening practices. Our analysis of cancer screening-related print news coverage during a four month period in 2005 suggests that the newsworthiness of new screening technologies may undermine public confidence in currently available and effective secondary prevention programs, while promoting tests whose effectiveness is debated or not yet established. Methods and results: We conducted a structured text analysis of 517 cancer-related news articles from 15 leading daily newspapers and a subsequent qualitative analysis of the 79 screening news articles. Screening articles were analyzed for content related to criteria for screening effectiveness. Content patterns for each type of screening and cancer were also noted. News coverage consistently conveyed screening as important and highlighted the need to protect and expand access to screening. At the same time, to the extent that story content was framed by the newsworthiness of new tests and technologies this often indirectly called into question effective and established protocols and programs without providing any actionable alternative. Conclusion: This analysis revealed unexpected messages about screening that are potentially problematic for cancer control. The cancer control community should continue efforts to understand and shape news coverage of screening in order to promote balanced and action-oriented content. Research has shown that Americans hold conflicting views regarding cancer—having a favorable opinion of screening while simultaneously feeling fatalistic about prevention. Our analysis of print news stories on cancer screening suggests that the determination of screening's “newsworthiness” is related to newly developed tests and protocols, which may create demand for new tests whose effectiveness is unknown and undermine confidence in established and effective screening programs.

Identification of novel large genomic rearrangements at the BRCA1 locus in Malaysian women with breast cancer

2010-04-30

Abstract: Background: The incidence of breast cancer has been on the rise in Malaysia. It is suggested that a subset of breast cancer cases were associated with germline mutation in breast cancer susceptibility (BRCA) genes. Most of the BRCA mutations reported in Malaysia were point mutations, small deletions and insertions. Here we report the first study of BRCA large genomic rearrangements (LGRs) in Malaysia. We aimed to detect the presence of LGRs in the BRCA genes of Malaysian patients with breast cancer. Methods: Multiplex ligation-dependent probe amplification (MLPA) for BRCA LGRs was carried out on 100 patients (60 were high-risk breast cancer patients previously tested negative/positive for BRCA1 and BRCA2 mutations, and 40 were sporadic breast cancer patients), recruited from three major referral centres, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ). Results: Two novel BRCA1 rearrangements were detected in patients with sporadic breast cancer; both results were confirmed by quantitative PCR. No LGRs were found in patients with high-risk breast cancer. The two large genomic rearrangements detected were genomic amplifications of exon 3 and exon 10. No BRCA2 genomic rearrangement was found in both high-risk and sporadic breast cancer patients. Conclusion: These results will be helpful to understand the mutation spectrum of BRCA1 and BRCA2 genes in Malaysian patients with breast cancer. Further studies involving larger samples are required to establish a genetic screening strategy for both high-risk and sporadic breast cancer patients.

MDM2 promoter polymorphism is associated with increased susceptibility to hepatocellular carcinoma in Turkish population

Hikmet Akkız, Ahmet Taner Sümbül, Süleyman Bayram, Aynur Bekar, Ersin Akgöllü — 2010-04-26

Abstract: Background: The mouse double minute 2 (MDM2) gene represents one of the central nodes in the p53 pathway. A naturally occurring T/G single nucleotide polymorphism (SNP) in the intronic promoter of MDM2, SNP309 (rs2279744), was shown to influence MDM2 expression and p53 activity. SNP in the promoter region of MDM2 gene has recently been shown to be associated with accelerated tumor formation in both hereditary and sporadic cancers in humans. In this study, we aim to evaluate the association of SNP309 with the risk of hepatocellular carcinoma (HCC) development among Turkish population. Methods: MDM2 SNP309 polymorphism was investigated in 110 confirmed subjects with HCC and 110 cancer-free control subjects matched on age, gender, smoking and alcohol consumption by using a polymerase chain reaction-restriction fragment length polymorphism assay. Results: The allele frequencies of case subjects (T, 0.48; G, 0.52) were significantly different from those of control subjects (T, 0.65; G, 0.35) (p=0.003). The proportion of GG genotype of the SNP309 in patients with HCC (26%) was significantly higher than that in patients without HCC (14%). We observed that compared with the TT genotype, the genotypes containing G allele [TG (OR, 2.19; 95% CI, 1.18–4.07; p=0.013) or GG (OR, 3.63; 95% CI, 1.65–8.00; p=0.001)] were associated with significant increased susceptibility to HCC. Conclusion: Our findings suggest that the MDM2 promoter SNP309 G allele is associated with presence of HCC in Turkish population.

The comparison of hair from gastric cancer patients and from healthy persons studied by infrared microspectroscopy and imaging using synchrotron radiation

2010-04-13

Abstract: Objective: The objective is to apply synchrotron-based FTIR microspectroscopy and imaging to human hair tissue and investigate the possibility of the method in gastric cancer research and diagnosis. Methods: Human hair from gastric cancer patients’ scalp and normal persons’ scalp were studied by synchrotron-based FTIR microspectroscopy and imaging. Results: The micro-spectra and imaging show the difference between the normal and malignant hair tissues. Obvious peak shift of symmetric phosphate band is observed in micro-spectra of medulla region for the hair tissue of gastric cancer patients. Chemical imaging shows the distributions of lipid and amide II/vsPO2− have changed in the gastric cancer cases. Conclusions: The study indicates that the hair tissue's infrared microspectroscopy and imaging using synchrotron will be a potentially useful method for rapid early gastric cancer diagnosis.

Influence of imaging on touch imprint cytology of breast lesions

Vimal Raj, T. Sivashanmugam, S. Gupta, K. Clarkson, E. Denton, M. Al-Attar — 2010-05-13

Abstract: Purpose: Touch imprint cytology (TIC) facilitates rapid diagnosis of breast diseases in women attending triple assessment clinics. Some pathologists, in our centre, feel that pathological interpretation of TIC slides is contentious when the lesions are radiologically indeterminate (R3), as these can lead to potentially higher false positive or false negative cytology results. We hypothesised that: ‘(R3) lesions are more likely to have higher false positive or false negative TIC and/or be inadequate for TIC assessment’. In other words, ‘imaging influences cytological classification especially when indeterminate’. Methods: Review of the data collected in our centre between December 2003 and July 2005. All patients who attended the one stop symptomatic breast clinic and had a TIC performed following an ultrasound (US) guided core biopsy (CB) were included. Demographic, radiological, cytological and core biopsy grading data were collected. Cytology grading was correlated with radiology classification to assess our hypothesis. Results: A total of 248 patients underwent 254 CB/TIC. The average patient's age of the group was 54 years (range of 29–95). On TIC, 186 (73%) were deemed malignant, 23(9%) benign while 33(13%) were inadequate for assessment. There was no false positive or false negative TIC. There was good correlation between TIC and CB results (p<0.0001). Thirty-three cases were inadequate (C1) for cytology assessment, of these16 (48.5%) were indeterminate on imaging. R3 lesions were 6 times more prone to have C1 cytology (p<0.0001). Conclusion: Touch imprint cytology is a reliable and efficient method in running a one stop breast clinic, with the backup of full tissue diagnosis. Careful selection of cases that would benefit from this technique is highly recommended as a significant number of radiologically indeterminate lesions are likely to be insufficient for cytological assessment. Further prospective trials are required to assess this further. Until then the diagnosis in this sub-group should depend on core biopsy.

Cholesterol and phytosterols differentially regulate the expression of caveolin 1 and a downstream prostate cell growth-suppressor gene

2010-04-28

Abstract: Background: The purpose of our study was to show the distinction between the apoptotic and anti-proliferative signaling of phytosterols and cholesterol-enrichment in prostate cancer cell lines, mediated by the differential transcription of caveolin-1, and N-myc downstream-regulated gene 1 (NDRG1), a pro-apoptotic androgen-regulated tumor suppressor. Methods: PC-3 and DU145 cells were treated with sterols (cholesterol and phytosterols) for 72h, followed by trypan blue dye-exclusion measurement of necrosis and cell growth measured with a Coulter counter. Sterol induction of cell growth-suppressor gene expression was evaluated by mRNA transcription using RT-PCR, while cell cycle analysis was performed by FACS analysis. Altered expression of Ndrg1 protein was confirmed by Western blot analysis. Apoptosis was evaluated by real time RT-PCR amplification of P53, Bcl-2 gene and its related pro- and anti-apoptotic family members. Results: Physiological doses (16μM) of cholesterol and phytosterols were not cytotoxic in these cells. Cholesterol-enrichment promoted cell growth (P<0.05), while phytosterols significantly induced growth-suppression (P<0.05) and apoptosis. Cell cycle analysis showed that contrary to cholesterol, phytosterols decreased mitotic subpopulations. We demonstrated for the first time that cholesterols concertedly attenuated the expression of caveolin-1 (cav-1) and NDRG1 genes in both prostate cancer cell lines. Phytosterols had the opposite effect by inducing overexpression of cav-1, a known mediator of androgen-dependent signals that presumably control cell growth or apoptosis. Conclusions: Cholesterol and phytosterol treatment differentially regulated the growth of prostate cancer cells and the expression of p53 and cav-1, a gene that regulates androgen-regulated signals. These sterols also differentially regulated cell cycle arrest, downstream pro-apoptotic androgen-regulated tumor suppressor, NDRG1 suggesting that cav-1 may mediate pro-apoptotic NDRG1 signals. Elucidation of the mechanism for sterol modulation of growth and apoptosis signaling may reveal potential targets for cancer prevention and/or chemotherapeutic intervention. Sterol regulation of NDRG1 transcription suggests its potential as biomarker for prediction of neoplasms that would be responsive to chemoprevention by phytosterols.

Alterations in p16 and p53 genes and chromosomal findings in patients with lung cancer: Fluorescence in situ hybridization and cytogenetic studies

Osman Demirhan, Deniz Taştemir, Serap Hastürk, Sedat Kuleci, İsmail Hanta — 2010-04-14

Abstract: Background: Chromosomal aberrations and instability of gene(s) are two factors related to the genetic instability of cancer cells. A loss of the tumor-suppressor function of the genes p16 and p53 is the most common event leading to the development of human cancers. Carcinoma of the lung is the leading cause of cancer deaths in the world. Chromosomal abnormalities in lung cancer may provide a valuable clue to the identification of target loci and culminate in a successful search for the major genes. The aim of this study was to investigate (i) alterations of the p16 and p53 genes and (ii) chromosomal aberrations in patients with small cell and non-small cell lung cancer by fluorescence in situ hybridization (FISH) and cytogenetic studies. Methods: We carried out cytogenetic analysis by Giemsa-banding in 18 cases. FISH probes for the p16 and p53 genes were also used on interphase nuclei to screen the alterations in these genes in lung cancer (LC).Results: We observed a high frequency of losses of the p16 – in 8/18 (44%) – and p53 – in 7/18 (39%) – genes in the cases with LC. A total of 18 patients showed predominantly numerical and structural aberrations. Among these two types, structural aberrations predominated and usually consisted of deletions, breaks, and fragilities in various chromosomes. Both structural and numerical changes were observed in almost all patients. Chromosomes 3 and 1 were found to be most frequently involved in structural abnormalities, followed by chromosomes 6, 9, and 8. Autosomal aneuploidies were also observed to be the most frequent (chromosomes 22, 19, 18, 20, 9, and 17), followed by those of the X and Y chromosomes. The expression of fragile sites was also found to be significantly higher in seven chromosomal regions: 3p14, 1q21, 1q12, 6q26, 9q13, 8q22, and 8q24. Conclusion: Our data confirmed that DNA damage and genomic instability may be factors contributing to the mutation profile and development of lung cancer. The patients who developed lung cancer showed a high frequency of loss of both p16 and p53, in addition to chromosomal aberrations. Tobacco could be a major carcinogenic factor in lung-cancer progression. The loss of p16 and p53, and increased incidence of autosomal aneuploidy and chromatid breaks, along with other chromosomal alterations, can contribute to the progression of the disease.

Extracellular matrix metalloproteinase inducer expression has an impact on survival in human bladder cancer

2010-04-26

Abstract: Aim: Extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to promote tumor invasion and metastasis via stimulating matrix metalloproteinase synthesis in neighboring fibroblasts, to enhance angiogenesis via vascular endothelial growth factor, to induce chemoresistant tumor cells via the production of hyaluronan, and to confer resistance of cancer cells to anoikis through inhibition of Bim. The purpose of this study was to investigate the expression of EMMPRIN in human primary bladder cancer and to evaluate its prognostic value. Methods: EMMPRIN expression patterns were detected by immunohistochemistry. In order to determine its prognostic value, overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan–Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results: Of the 101 cases with bladder cancers, 68 (67.3%) cases were positive for EMMPRIN expression. When categorized into negative vs. positive expression, EMMPRIN was associated with the stage (p=0.006), the grade (p=0.002), carcinoma in situ (p=0.01), the recurrence (p=0.009), the progression (p=0.009), and the death (p=0.01) of patients with bladder cancer. Moreover, positive EMMPRIN expression clearly predicted poorer PFS (p=0.008) and OS (p=0.006). In the multivariate analysis, positive EMMPRIN expression was an independent prognostic factor for PFS (p=0.03) and OS (p=0.03). Conclusion: EMMPRIN expression was greater in bladder cancers than in the adjacent normal tissues and may be a useful prognostic marker for patients with bladder cancer.

Factors affecting pattern of care and survival in a population-based cohort of non-small-cell lung cancer incident cases

2010-04-21

Abstract: Objective: To analyze the role of sociodemographic factors as determinants of the initial pattern of care and survival in incident NSCLC cases. Methods: We linked 2298 incident NSCLC cases, identified by the Piedmont Cancer Registry of Turin (PCRT) with administrative health records to identify the initial pattern of care. Because stage of disease strongly influences pattern of care and prognosis of NSCLC, all the analyses were stratified according to stage (early and advanced). The association between the set of patient's characteristics and the probability of accessing a specific pattern of care was analysed with a multivariable multinomial logistic regression model. Survival was analysed with the Cox proportional hazard model. Results: In the early stage group, presence of comorbidities, older age and low educational level were all associated with a lower probability of receiving surgery. These same factors, as well as being unmarried, were associated with higher probability of receiving other non-curative care only. The effects of comorbidities and low educational level as barriers to receiving more effective patterns of care were not relevant in the advanced stage group. When controlling for initial patterns of care, in the early stage group, an age older than 75 years and being unmarried were negative prognostic factors, while survival was completely independent from educational level. Among patients with an advanced stage of disease, only comorbidities had a negative impact on survival. Conclusion: Appropriate lung cancer care is affected by sociodemographic factors. Greater attention to social and health programs is recommended to improve the timeliness of diagnosis, the staging of potentially resectable patients, and to implement more comprehensive multidisciplinary evaluations of those who may benefit from curative treatments.

TYMS, MTHFR, p53 and MDR1 gene polymorphisms in breast cancer patients treated with adjuvant therapy

2010-03-25

Abstract: Purpose: The distribution of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms was investigated in 80 consecutive breast cancer patients treated with adjuvant chemotherapy. Results: Observed allelic frequencies were: TSER, (2) 0.55 and (3) 0.45; MTHFR C677T, (C) 0.65 and (T) 0.35; p53 Arg72Pro, (Arg) 0.76 and (Pro) 0.24; MDR1 C3435T, (C) 0.51 and (T) 0.49. MTHFR C677T was found to be a strong predictor of the presence of multifocal tumour (odds ratio, 4.1; 95% CI, 1.1–15.7; P=0.035). Conclusion: Our data indicate that breast cancer patients with the C/C variant may present multifocal tumour most frequently.

Multi-chaperone-peptide-rich mixture from colo-carcinoma cells elicits potent anticancer immunity

2010-04-12

Abstract: Background: Chaperones play an important role in inducing anti-cancer immunity. To explore the probability of using chaperone-peptide-rich complexes extracted from colo-carcinoma cells as anti-cancer vaccine, we extracted and prepared chaperone-peptide-rich complexes from CT26 cells, which were subsequently investigated on anti-cancer efficacy. Methods: The crude extracts of the CT26 cells treated with heat and Trichosanthin were precipitated with salt and dialyzed to remove proteins below 50kDa and above 300kDa in molecular weight; the proteins with the molecular weights in 70kDa, 90kDa, 95kDa, 110kDa and 170kDa were collected through gel filtration and SDS-PAGE. After confirmation, the purified proteins were used to determine their effects on lymphocyte proliferation, the activities of NK and CTL, tumor suppression and the tumor-bearing mouse survival. Results: The majority of the chaperone-peptides of anti-cancer immunity in CT26 cells, including HSP70-antigen peptide, HSP90-antigen peptide, gp96-antigen peptide, HSP-110 antigen peptide, HSP170-antigen peptide, was satisfactorily extracted that the multi-chaperone-peptide-rich mixtures were obtained. All the mixtures prepared could elicit lymphocyte proliferation, enhance the activities of CTL and NK, reinforce the tumor suppression and prolong the mouse survival. Conclusions: The multi-chaperone-peptide-rich mixtures could be prepared via dialysis and gel filtration combining with SDS-PAGE. Both the heat stress and Trichosanthin could induce and increase the mixtures, of which that treated by 42°C heat and Trichosanthin was found to possess the strongest anti-cancer efficacy.

Abstracting stage in population-based cancer registries: The example of oral cavity and oropharynx cancers

Marianna de Camargo Cancela, François Chapuis, Maria Paula Curado — 2010-04-30

Abstract: Population-based cancer registries (PBCRs) are instruments to provide cancer incidence to promote cancer control and etiological research. A setting of mandatory (standard) variables is routinely collected for patient and tumor. One recommended variable is tumor stage, which supplies information on disease status and is an essential prognostic factor. However, it is not considered as necessary information to be collected by the PBCR. There are studies showing the value of stage as a prognostic variable to evaluate survival, socio-economic status, race and ethnics differences. Our aim is to analyze the feasibility of PBCRs in abstracting TNM for oral cavity and oropharynx. These topographies were selected due to the clinical accessibility of stage tumors by visual inspection and palpation. About 23% of the PBCRs who contributed to CI5-IX indicated their collection of TNM stage for all cancer sites. We analyzed 23,935 cases of oral cavity (OCC) and oropharynx cancer (OPC) from 13 PBCRs. Complete TNM stage for OCC was 52.7% for males and 47.6% for females; for OPC, it was 56% in both genders. Incomplete stage on OCC and OPC ranged from 22 to 25%. Missing was about 18–27% (most common in oral cavity). Missing stage was significantly higher in males for OCC aged ≥70 years, OR 1,64 (1.39–1.94). Our results demonstrate that OPC tend to have more stage, when compared with OCC. Even if it can be diagnosed by visual inspection, these results highlight the fact that information on stage can be a reliable indicator of access to healthcare and diagnosis awareness. Our results demonstrate that is feasible for PBCR to collect stage, although improving completeness of this information needs further technical training and international recommendation to adopt TNM stage as a standard variable for the PBCRs.

Might early baldness protect from prostate cancer by increasing skin exposure to ultraviolet radiation?

Peter Kabai — 2010-04-30

In a recent issue of Cancer Epidemiology, Wright et al. reported that early-onset male pattern baldness (MPB) is linked to reduced risk of prostate cancer (PCa). Relationship between MPB and PCa has been a controversial issue. In most studies MPB was shown to be a risk factor in PCa and such findings have been explained by the similarity of mechanism in the development of those two conditions. The inverse relationship between MPB and risk of PCa found by Wright et al. is difficult to explain. The authors suggest two specific mechanisms linking low level of MPB and higher incidence of PCa. First they cite Hayes et al. who found that carriers of a specific allelic variant of the 5α-reductase type II gene (A49T A) were at higher risk of prostate cancer and lower risk of vertex and frontal balding. Although the results of Hayes et al. are congruent with those of Wright et al. they do not offer an explanation, because that variant is rare. Secondly, Wright et al. noted that the 5α-reductase inhibitor “not only lowers DHT but also raises testosterone concentrations 7–10-fold”. Although it is true that testosterone accumulates in the prostate if not converted to DHT, reductase inhibitors are effective in the treatment of PCa as well as MPB because DHT and not testosterone is the key factor in the development of both conditions.

Cancer Epidemiology

Editorial Board

Contents

Regional trends in prostate cancer incidence, treatment with curative intent and mortality in Norway 1980–2007

Years of potential life lost caused by prostate cancer deaths in the United States—Projection from 2004 through 2050

Geographical analysis of cancer incidence in Ireland: A comparison of two Bayesian spatial models

The validity and reliability of the Socioeconomic Status Instrument for assessing prostate cancer patients

Occupational exposure to hexavalent chromium and cancers of the gastrointestinal tract: A meta-analysis

Prenatal exposure to medicines and the risk of childhood brain tumor

Effect of tobacco chewing, tobacco smoking and alcohol on all-cause and cancer mortality: A cohort study from Trivandrum, India

Does consanguinity lead to decreased incidence of breast cancer?

Effect of family history of cancers and environmental factors on risk of nasopharyngeal carcinoma in Guangdong, China

Assessment of women's risk factors for breast cancer and predictors of the practice of breast examination in two rural areas near Ibadan, Nigeria

Estimating key parameters in periodic breast cancer screening—Application to the Canadian National Breast Screening Study data

Print news coverage of cancer: What prevention messages are conveyed when screening is newsworthy?

Identification of novel large genomic rearrangements at the BRCA1 locus in Malaysian women with breast cancer

MDM2 promoter polymorphism is associated with increased susceptibility to hepatocellular carcinoma in Turkish population

The comparison of hair from gastric cancer patients and from healthy persons studied by infrared microspectroscopy and imaging using synchrotron radiation

Influence of imaging on touch imprint cytology of breast lesions

Cholesterol and phytosterols differentially regulate the expression of caveolin 1 and a downstream prostate cell growth-suppressor gene

Alterations in p16 and p53 genes and chromosomal findings in patients with lung cancer: Fluorescence in situ hybridization and cytogenetic studies

Extracellular matrix metalloproteinase inducer expression has an impact on survival in human bladder cancer

Factors affecting pattern of care and survival in a population-based cohort of non-small-cell lung cancer incident cases

TYMS, MTHFR, p53 and MDR1 gene polymorphisms in breast cancer patients treated with adjuvant therapy

Multi-chaperone-peptide-rich mixture from colo-carcinoma cells elicits potent anticancer immunity

Abstracting stage in population-based cancer registries: The example of oral cavity and oropharynx cancers

Might early baldness protect from prostate cancer by increasing skin exposure to ultraviolet radiation?