The purpose of this article is to facilitate access of biomedical researchers to human tissues by describing the types of tissue resources available to researchers, common problems with tissue requests that may limit tissue availability to specific investigators, and steps that can be taken to simplify requests to avoid these problems and enhance access to tissue. Types of human tissue resources available to investigators are described and reviewed, and the experience of the University of Alabama Tissue Collection and Banking Facility (TCBF) is described. Our experience indicates that typical problems with requests for tissue fall into the following categories: (1) size and number of specimens, (2) type (rarity and availability), (3) time constraints, (4) demand versus supply, (5) limitations and goals of the resource, and (6) time and resources that can be devoted to a specific request. Investigators should review their requests for human tissues to support their research if they are not receiving adequate quantities of tissue. This review is best accomplished by discussing their requests with the tissue resource and correcting specific limitations that block access to the tissues they need. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1676–9)

This review discusses the biology and the methods of assessment of apoptosis, of which, the monoclonal antibody M30 would seem to be the most useful; the role of apoptosis in the etiology of colorectal cancer; and its use as a marker to monitor the beneficial effects of chemopreventative interventions to reduce the development of colorectal cancer within the context of clinical trials. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1680–7)

Background: Previous studies have documented significant variations in colorectal cancer incidence rates and trends regionally and across countries. However, no study has examined the worldwide pattern using the most recently updated incidence data from the IARC.

Methods: We obtained sex-specific colorectal cancer incidence for 1953-57 through 1998-2002 by cancer registry from Cancer Incidence in Five Continents (CI5) databases. For 51 cancer registries with long-term incidence data, we assessed the change in the incidence rates over the past 20 years by calculating the ratio of the incidence rates in 1998-2002 to that in 1983-87.

Results: Colorectal cancer incidence rates for both males and females statistically significantly increased from 1983-87 to 1998-2002 for 27 of 51 cancer registries considered in the analysis, largely confined to economically transitioning countries including Eastern European countries, most parts of Asia, and select countries of South America. These increases were more prominent for men than for women. We also observed substantial variations in colorectal cancer incidence trends within countries such as Japan. Similarly, trends in Israel and Singapore varied significantly according to ethnicity. The United States is the only country where colorectal cancer incidence rates declined in both males and females.

Conclusions: Colorectal cancer incidence rates continue to increase in economically transitioning countries, with incidence rates among men in the Czech Republic and Slovakia exceeding the peak incidence observed in the United States and other long-standing developed nations. Targeted prevention and early detection programs could help reverse the trend in these countries. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1688–94)

The recent, accelerated decline in colorectal cancer incidence rates has largely been attributed to an increase in screening rates among adults 50 years and older. We used data from 13 Surveillance, Epidemiology, and End Results cancer registries to report on colorectal cancer incidence trends from 1992 through 2005 among adults under age 50 years, for whom screening is not recommended for persons at average risk, by sex, race/ethnicity, age, stage at diagnosis, and anatomic subsite. Overall, incidence rates of colorectal cancer per 100,000 young individuals (ages 20-49 years) increased 1.5% per year in men and 1.6% per year in women from 1992 to 2005. Among non-Hispanic Whites, rates increased for both men and women in each 10-year age grouping (20-29, 30-39, and 40-49 years) and for every stage of diagnosis. The increase in incidence among non-Hispanic Whites was predominantly driven by rectal cancer, for which there was an average increase of 3.5% per year in men and 2.9% per year in women over the 13-year study interval. In contrast to the overall decreasing trend in colorectal cancer incidence in the United States, rates are increasing among men and women under age 50 years. Further studies are necessary to elucidate causes for this trend and identify potential prevention and early detection strategies. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1695–8)

Background: Self-reported screening behaviors from national surveys often overestimate screening use, and the amount of overestimation may vary by demographic characteristics. We examine self-report bias in mammography screening rates overall, by age, and by race/ethnicity.

Methods: We use mammography registry data (1999-2000) from the Breast Cancer Surveillance Consortium to estimate the validity of self-reported mammography screening collected by two national surveys. First, we compare mammography use from 1999 to 2000 for a geographically defined population (Vermont) with self-reported rates in the prior two years from the 2000 Vermont Behavioral Risk Factor Surveillance System. We then use a screening dissemination simulation model to assess estimates of mammography screening from the 2000 National Health Interview Survey.

Results: Self-report estimates of mammography use in the prior 2 years from the Vermont Behavioral Risk Factor Surveillance System are 15 to 25 percentage points higher than actual screening rates across age groups. The differences in National Health Interview Survey screening estimates from models are similar for women 40 to 49 and 50 to 59 years and greater than for those 60 to 69, or 70 to 79 (27 and 26 percentage points versus 14, and 14, respectively). Overreporting is highest among African American women (24.4 percentage points) and lowest among Hispanic women (17.9) with non-Hispanic White women in between (19.3). Values of sensitivity and specificity consistent with our results are similar to previous validation studies of mammography.

Conclusion: Overestimation of self-reported mammography usage from national surveys varies by age and race/ethnicity. A more nuanced approach that accounts for demographic differences is needed when adjusting for overestimation or assessing disparities between populations. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1699–705)

New Zealand Maori, Pacific, and Asian people develop melanoma less frequently than New Zealand Europeans, but little is known about melanomas that develop in these people. We examined the characteristics of melanoma in these minority ethnic groups in New Zealand. In 2007, all first primary melanomas diagnosed from January 1996 to December 2006 were extracted from the New Zealand Cancer Registry database. Melanoma was more commonly diagnosed in Maori than Asian or Pacific peoples. Age-adjusted incidence rates increased annually from 1996 to 2006 by 0.37 per 100,000 in the total population and 0.20 per 100,000 in Maori, a 12% (from 30.9 to 34.6) and 90% (from 2.3 to 4.3) increase, respectively, over the 11 years. Nodular melanoma occurred more often in Maori (15.9%) and Pacific peoples (17.1%) compared with Asians (8.7%) and New Zealand Europeans (10.5%). In Pacific peoples, acral lentiginous melanoma (22.9%) was the most common subtype. The median thickness of melanoma was 0.78 mm in New Zealand Europeans, 1.2 mm in Maori, 2.5 mm in Pacific peoples, and 0.73 mm in Asians (P < 0.001, difference in medians). Thirty-seven percent of melanomas in Pacific peoples were >4 mm thick compared with 7.9% in New Zealand Europeans. About 13% of Asians and 11% of Pacific peoples, compared with 4% of New Zealand Europeans with melanoma, were diagnosed by histology of metastases rather than the primary lesion. Minority ethnicities in New Zealand have a higher than expected risk of thick and more advanced melanoma, with poorer prognosis. Melanoma campaigns should include messages that incorporate the unique features of melanoma in minorities. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1706–13)

Background: Inhibitors of histone deacetylases (HDAC) have shown promise as targeted cancer therapy. Valproate, an older anticonvulsant, has been shown to possess HDAC inhibitory activity. We undertook this case-control study to clarify whether long-term users of valproate had a reduced cancer incidence. If so, it would support HDAC inhibition as a pharmacologic principle in chemoprevention.

Methods: We identified 149,417 incident cancer cases in Denmark during the study period 2000 through 2005, and 597,668 age- and gender-matched controls. Data on history of cancer, past hospital admission diagnoses, and prescription history were obtained from the Danish Cancer Registry, the Danish National Patient Registry, and the Danish Prescription Registry. Primary exposure to valproate was defined as a cumulative dose of minimum 1,500 g within the past 5 years. Confounders were controlled by conditional logistic regression.

Results: Among the cases and controls, 81 (0.05%) and 260 (0.04%), respectively, were long-term users of valproate. For cancer overall, the crude and adjusted odds ratios were 1.25 [95% confidence interval (95% CI), 0.97-1.60] and 1.21 (95% CI, 0.95-1.56), respectively. Subgroup analyses revealed no dose or duration effect for overall cancer incidence, and no specific cancer site was found to be inversely associated with long-term use of valproate. For lung cancer, we found a positive but imprecise association (adjusted odds ratio, 2.32; 95% CI, 1.12-4.79).

Conclusion: Long-term valproate use is not associated with a reduced cancer risk. Our study does not support HDAC inhibition as a pharmacologic principle for general chemoprevention. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1714–9)

Frequent exposure to nickel compounds has been considered as one of the potential causes of human lung cancer. However, the molecular mechanism of nickel-induced lung carcinogenesis remains obscure. In the current study, slight S-phase increase, significant G₂/M cell cycle arrest, and proliferation blockage were observed in human bronchial epithelial cells (Beas-2B) upon nickel exposure. Moreover, the induction of cyclin D1 and cyclin E by nickel was shown for the first time in human pulmonary cells, which may be involved in nickel-triggered G₁/S transition and cell transformation. In addition, we verified that hypoxia-inducible factor-1, an important transcription factor of nickel response, was not required for the cyclin D1 or cyclin E induction. The role of p53 in nickel-induced G₂/M arrest was excluded, respecting that its protein level, ser¹⁵ phosphorylation, and transcriptional activity were not changed in nickel response. Further study revealed that cyclin A was not activated in nickel response, and cyclin B1, which not only promotes G₂/M transition but also prevents M-phase exit of cells if not degraded in time, was up-regulated by nickel through a manner independent of hypoxia-inducible factor. More importantly, our results verified that overexpressed cyclin B1, veiling the effect of cyclin D1 or cyclin E, mediated nickel-caused M-phase blockage and cell growth inhibition, which may render pulmonary cells more sensitive to DNA damage and facilitates cancer initiation. These results will not only deepen our understanding of the molecular mechanism involved in nickel carcinogenecity, but also lead to the further study on chemoprevention of nickel-associated human cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1720–9)

Fruit and vegetable consumption has been hypothesized to reduce the risk of renal cell cancer. We conducted a pooled analysis of 13 prospective studies, including 1,478 incident cases of renal cell cancer (709 women and 769 men) among 530,469 women and 244,483 men followed for up to 7 to 20 years. Participants completed a validated food-frequency questionnaire at baseline. Using the primary data from each study, the study-specific relative risks (RR) were calculated using the Cox proportional hazards model and then pooled using a random effects model. We found that fruit and vegetable consumption was associated with a reduced risk of renal cell cancer. Compared with <200 g/d of fruit and vegetable intake, the pooled multivariate RR for ≥600 g/d was 0.68 [95% confidence interval (95% CI) = 0.54-0.87; P for between-studies heterogeneity = 0.86; P for trend = 0.001]. Compared with <100 g/d, the pooled multivariate RRs (95% CI) for ≥400 g/d were 0.79 (0.63-0.99; P for trend = 0.03) for total fruit and 0.72 (0.48-1.08; P for trend = 0.07) for total vegetables. For specific carotenoids, the pooled multivariate RRs (95% CIs) comparing the highest and lowest quintiles were 0.87 (0.73-1.03) for -carotene, 0.82 (0.69-0.98) for β-carotene, 0.86 (0.73-1.01) for β-cryptoxanthin, 0.82 (0.64-1.06) for lutein/zeaxanthin, and 1.13 (0.95-1.34) for lycopene. In conclusion, increasing fruit and vegetable consumption is associated with decreasing risk of renal cell cancer; carotenoids present in fruit and vegetables may partly contribute to this protection. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1730–9)

The U.S. active-duty military population may differ from the U.S. general population in its exposure to cancer risk factors and access to medical care. Yet, it is not known if cancer incidence rates differ between these two populations. We therefore compared the incidence of four cancers common in U.S. adults (lung, colorectal, prostate, and breast cancers) and two cancers more common in U.S. young adults (testicular and cervical cancers) in the military and general populations. Data from the Automated Central Tumor Registry (ACTUR) of the Department of Defense and the nine cancer registries of the Surveillance, Epidemiology and End Results (SEER) of the National Cancer Institute for the years 1990 to 2004 for persons with ages 20 to 59 years were analyzed. Incidence rates were significantly lower in the military population for colorectal cancer in White men, lung cancer in White and Black men and White women, and cervical cancer in Black women. In contrast, incidence rates of breast and prostate cancers were significantly higher in the military among Whites and Blacks. Incidence rates of testicular cancer did not differ between ACTUR and SEER. Although the numbers of diagnoses among military personnel were relatively small for temporal trend analysis, we found a more prominent increase in prostate cancer in ACTUR than in SEER. Overall, these results suggest that cancer patterns may differ between military and nonmilitary populations. Further studies are needed to confirm these findings and explore contributing factors. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1740–5)

In spite of their anticarcinogenic potential, the effect of coffee and green tea consumption on the risk of liver cancer has not been clarified prospectively in consideration of hepatitis C (HCV) and B virus (HBV) infection. We examined whether coffee and green tea consumption was associated with a reduced risk of liver cancer by hepatitis virus infection status in the Japan Public Health Center-Based Prospective Study Cohort II. A total of 18,815 subjects ages 40 to 69 years participating in a questionnaire and health checkup survey in 1993 to 1994 were followed for the incidence of liver cancer through 2006. A total of 110 cases of liver cancer were newly documented. Hazard ratios for coffee and green tea consumption categories were calculated with a Cox proportional hazards model. Compared with almost never drinkers, increased coffee consumption was associated with a reduced risk of liver cancer in all subjects (hazard ratio for <1, 1-2, and ≥3 cups/d; P_trend = 0.67, 0.49, 0.54, and 0.025). A similar risk tendency was observed in those with either or both HCV and HBV infection. In contrast, no association was observed between green tea consumption and the risk of liver cancer in all subjects. Our results suggest that coffee consumption may reduce the risk of liver cancer regardless of HCV and HBV infection status, whereas green tea may not reduce this risk.(Cancer Epidemiol Biomarkers Prev 2009;18(6):1746–53)

Background: Mammographic density has been found to be strongly associated with risk of breast cancer. We have assessed a novel method of assessing breast tissue that is fully automated, does not require an observer, and measures the volume, rather than the projected area, of the relevant tissues in digitized screen-film mammogram.

Methods: Sixteen mammography machines in seven locations in Toronto were calibrated to allow the estimation of the proportion of radiologically dense (stromal and epithelial tissue) and nondense (fatty) tissue represented in each pixel of the mammographic image. This information was combined with a measurement of breast thickness to calculate the volumes of these tissues. Women with newly diagnosed breast cancer (cases) identified on these mammography machines during the years 2000 to 2003 were compared with other women of the same age who did not have breast cancer (controls).

Results: Three hundred sixty-four cases and 656 controls were recruited, epidemiologic data were collected, screen-film mammograms were digitized and measured using both a computer-assisted thresholding method, and the new measure of the volume of density. After adjustment for other risk factors, the odds ratio for those in the 5th quintile compared with the 1st quintile was 1.98 (95% confidence interval, 1.3-3.1) for the volume measure and 1.86 (95% CI, 1.1-3.0) for the area measurement. After inclusion of the volume and area measures in a predictive model, the volume measure lost significance, whereas the area measure remained significant.

Conclusions: Contrary to our expectations, measurement of the volume of breast tissue did not improve prediction of breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1754–62)

Background: National incidence rates for lobular and ductal breast cancers have not been available previously. Evidence suggests that the increased risk of breast cancer associated with combined hormone replacement therapy use is higher for invasive lobular cancers (ILC) than for invasive ductal cancers (IDC). This study provides U.S. incidence rates for these histologic types for both in situ and invasive cancers and assesses changes in the incidence of these cancers over time.

Methods: Data for this study included incident ductal and lobular breast cancer cases diagnosed from 1999 through 2004 in central cancer registries in 44 states and the District of Columbia from the National Program of Cancer Registries and the Surveillance, Epidemiology, and End Results program. We estimated incidence per 100,000 women by 10-year age groups, race, and ethnicity. We also assessed the percent change in invasive and in situ cancer incidence over time.

Results: We observed distinct differences in the change of incidence over time between in situ and invasive lobular and ductal breast cancers. The age-adjusted rates of ILC and IDC declined an average of 4.6% and 3.3% per year, respectively. Overall, ILC decreased 20.5% from 1999 to 2004. The patterns of ductal and lobular in situ cancer incidence were not consistent over time, and the total change was negligible.

Conclusion: The declines in ILC observed in our study are consistent with a decrease in cancer incidence related to a reduced use of combined hormone replacement therapy. However, other factors could also be responsible for these changes. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1763–9)

Matrix metalloproteinase-2 (MMP-2) is a well-known mediator of cancer metastasis but is also thought to be involved in several aspects of cancer development, including cell growth and inflammation. We comprehensively characterized genetic variation across the MMP-2 gene and evaluated associations with breast cancer risk using a two-phase (phase 1 and phase 2) study design. A total of 39 polymorphisms were genotyped among 6,066 Chinese women participating in the Shanghai Breast Cancer Study, a population-based case-control study. Two MMP-2 promoter polymorphisms were found to have consistent results between phase 1 and phase 2 participants, and to be significantly associated with breast cancer risk among all genotyped participants. Minor allele homozygotes for rs11644561 (G/A) were found to have a decreased risk of breast cancer [odds ratio (OR), 0.6; 95% confidence interval (CI), 0.3-1.0] compared with major allele homozygotes, as were minor allele homozygotes for rs11643630 (T/G) compared with major allele homozygotes (OR, 0.8; 95% CI, 0.7-1.0). When analyzed together, a rare haplotype (4.4%) with both rs11644561 A and rs11643630 G was found to have a significantly reduced risk of breast cancer (OR, 0.6; 95% CI, 0.4-0.8). In addition, rare allele homozygotes for rs243865 (–1306 C/T) tended to have an increased risk of breast cancer (OR, 1.4; 95% CI, 0.9-2.4). Together, these findings support a role for MMP-2 genetic variation in breast cancer susceptibility. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1770–6)

Background: We describe the prevalence of 14 common types [human papillomavirus (HPV)-6/11/16/18/31/33/35/39/45/51/52/56/58/59] in vulvar intraepithelial neoplasia grades 1 to 3 (VIN 1-3) and HPV genotype–specific infection in relation to the development of VIN 1-3.

Methods: Data were analyzed from women enrolled in the placebo arms of three randomized double-blind trials. Anogenital examinations, including collection of labial/vulvar/perineal/perianal swabs, occurred at day 1 and every 6 to 12 months through 48 months. Lesions that were possibly, probably, or definitely HPV related or of unknown etiology were biopsied. Biopsies and swabs were HPV typed. Biopsies were read for endpoint determination (VIN 1-3) by up to four pathologists.

Results: Incident infection with HPV-16 was the most common (6.0/100 person-years). The mean time from incident infection to the development of VIN 1-3 was 18.5 months (95% confidence interval, 13.4-23.6). HPV-6 or -11 was observed in 64.5% of VIN 1 and 29.0% of VIN 2/3, whereas HPV-16 was observed in 6.5% of VIN 1 and 64.5% of VIN 2/3.

Conclusion: A vaccine that includes both low- and high-risk types could prevent more than half of VIN 1-3 lesions, including the precursor lesions to HPV-related vulvar carcinoma. Understanding the incidence and duration of vulvar HPV infection and risk for progression to VIN 1-3 may inform therapeutic decisions for vulvar disease and mathematical models that assess the cost-effectiveness of vaccination. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1777–84)

An association between high intake of folate and reduced risk of cancer has been suggested by previous research. However, epidemiologic data from cohort studies regarding the relationship between dietary folate and pancreatic cancer are sparse and inconsistent. We examined the association between dietary folate intake and risk of pancreatic cancer within the Netherlands Cohort Study on diet and cancer. Men and women (120,852), ages 55 to 69 years, were recruited. Information on diet was collected at baseline by means of food frequency questionnaires, and the cohort was followed for 13.3 years. Total folate and vitamer intake were calculated using folate contents of food items derived from a validated liquid chromatography trienzyme method. Cases (n = 363) were identified by record linkage with regional cancer registries and the Dutch National Database of Pathology Reports. A case-cohort approach was used using the follow-up data of a random subcohort (n = 5,000) identified at the onset of the cohort. Multivariable hazard ratios with 95% confidence intervals were estimated using Cox proportional hazards model. After adjusting for age, gender, smoking status, number of years smoked, number of cigarettes smoked per day, and intake of added sugar multivariate hazard ratio comparing the highest and lowest quintiles of folate intake for pancreatic cancer risk was 1.37 (confidence interval, 0.97-1.94; P_trend = 0.07). When folate vitamers were analyzed separately, results did not show a difference in association. Our results do not support a protective association of total dietary folate or individual folate vitamers on the risk of pancreatic cancer.(Cancer Epidemiol Biomarkers Prev 2009;18(6):1785–91)

Studies have examined the prognostic relevance of reproductive factors before breast cancer diagnosis, but most have been small and their overall findings inconclusive. Associations between reproductive risk factors and all-cause mortality after breast cancer diagnosis were assessed with the use of a population-based cohort of 3,107 women of White European ancestry with invasive breast cancer (1,130 from Melbourne and Sydney, Australia; 1,441 from Ontario, Canada; and 536 from Northern California, United States). During follow-up with a median of 8.5 years, 567 deaths occurred. At recruitment, questionnaire data were collected on oral contraceptive use, number of full-term pregnancies, age at first full-term pregnancy, time from last full-term pregnancy to breast cancer diagnosis, breastfeeding, age at menarche, and menopause and menopausal status at breast cancer diagnosis. Hazard ratios for all-cause mortality were estimated with the use of Cox proportional hazards models with and without adjustment for age at diagnosis, study center, education, and body mass index. Compared with nulliparous women, those who had a child up to 2 years, or between 2 and 5 years, before their breast cancer diagnosis were more likely to die. The unadjusted hazard ratio estimates were 2.75 [95% confidence interval (95% CI), 1.98-3.83; P < 0.001] and 2.20 (95% CI, 1.65-2.94; P < 0.001), respectively, and the adjusted estimates were 2.25 (95% CI, 1.59-3.18; P < 0.001) and 1.82 (95% CI, 1.35-2.46; P < 0.001), respectively. When evaluating the prognosis of women recently diagnosed with breast cancer, the time since last full-term pregnancy should be routinely considered along with other established host and tumor prognostic factors, but consideration of other reproductive factors may not be warranted. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1792–7)

Purpose: To evaluate molecular and immunohistochemical markers to develop a molecular grading of urothelial bladder cancer and to test these markers in voided urine samples.

Experimental Design: 255 consecutive biopsies from primary bladder cancer patients were evaluated on a tissue microarray. The clinical parameters gender, age, adjacent carcinoma in situ, and multifocality were collected. UroVysion fluorescence in situ hybridization (FISH) was done. Expression of cytokeratin 20, MIB1, and TP53 was analyzed by immunohistochemistry. Fibroblast growth factor receptor 3 (FGFR3) status was studied by SNaPshot mutation detection. Results were correlated with clinical outcome by Cox regression analysis. To assess the predictive power of different predictor subsets to detect high grade and tumor invasion, logistic regression models were learned. Additionally, voided urine samples of 119 patients were investigated. After cytologic examination, urine samples were matched with their biopsies and analyzed for loss of heterozygosity (LOH), FGFR3 mutation, polysomy, and p16 deletion using UroVysion FISH. Receiver operator characteristic curves for various predictor subsets were plotted.

Results: In biopsies, high grade and solid growth pattern were independent prognostic factors for overall survival. A model consisting of UroVysion FISH and FGFR3 status (FISH + FGFR3) predicted high grade significantly better compared with a recently proposed molecular grade (MIB1 + FGFR3). In voided urine, the combination of cytology with LOH analysis (CYTO + LOH) reached the highest diagnostic accuracy for the detection of bladder cancer cells and performed better than cytology alone (sensitivity of 88.2% and specificity of 97.1%).

Conclusions: The combination of cytology with LOH analysis could reduce unpleasant cystoscopies for bladder cancer patients. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1798–806)

Background: In the past two decades, the incidence of breast cancer in young Taiwanese females has been rapidly increasing, approaching the risk level of western countries. As a first step to investigate the possible etiology, we examined the molecular subtypes of female breast cancer in Taiwan.

Methods: This study included 1,028 consecutive patients with breast cancer diagnosed in National Taiwan University Hospital between 2004 and 2006. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2, cytokeratin 5/6, and epidermal growth factor receptor expression and/or gene amplification were analyzed.

Results: Younger (≤50 years) breast cancer patients had a higher prevalence of luminal A (67% versus 57%; P < 0.001) and a lower prevalence of basal-like subtype (9% versus 17%; P < 0.001) compared with older (>50 years) patients. The higher prevalence of luminal A subtype was mainly attributed to a higher ER (75% versus 63%; P < 0.001) and PR (47% versus 33%; P < 0.001) expression rate in younger patients than older patients. Tumors with histologic grade 3 were less prevalent in younger patients than in older patients (23% versus 30%; P = 0.01). For very young (<35 years) patients, the molecular subtype distribution, ER and/or PR expression rate, and histologic grade were not significantly different from those of less young (35-50 years) patients.

Conclusions: Young breast cancer patients in Taiwan are characterized by a high prevalence of luminal A subtype and low prevalence of histologic grade 3 tumor and/or basal-like subtype. These features are distinct from young breast cancer patients in western countries. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1807–14)

Single nucleotide polymorphisms (SNP) at 11q13 were recently implicated in prostate cancer risk by two genome-wide association studies and were consistently replicated in multiple study populations. To explore prostate cancer association in the regions flanking these SNPs, we genotyped 31 tagging SNPs in a ~110 kb region at 11q13 in a Swedish case-control study (Cancer of the Prostate in Sweden), including 2,899 cases and 1,722 controls. We found evidence of prostate cancer association for the previously implicated SNPs including rs10896449, which we termed locus 1. In addition, multiple SNPs on the centromeric side of the region, including rs12418451, were also significantly associated with prostate cancer risk (termed locus 2). The two groups of SNPs were separated by a recombination hotspot. We then evaluated these two representative SNPs in an additional ~4,000 cases and ~3,000 controls from three study populations and confirmed both loci at 11q13. In the combined allelic test of all four populations, P = 4.0 x 10^–11 for rs10896449 at locus 1 and P = 1.2 x 10^–6 for rs12418451 at locus 2, and both remained significant after adjusting for the other locus and study population. The prostate cancer association at these two 11q13 loci was unlikely confounded by prostate-specific antigen (PSA) detection bias because neither SNP was associated with PSA levels in controls. Unlike locus 1, in which no known gene is located, several putative mRNAs are in close proximity to locus 2. Additional confirmation studies at locus 2 and functional studies for both loci are needed to advance our knowledge on the etiology of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1815–20)

DNA damage induced by benzene reactive metabolites is thought of as an important mechanism underlying benzene hematotoxicity and genotoxicity, and genetic variation in cell-cycle control genes may contribute to susceptibility to chronic benzene poisoning (CBP). Using a case-control study that included 307 benzene-poisoned patients and 299 workers occupationally exposed to benzene in south China, we aimed to investigate the association between genetic polymorphisms of p53 and p21 and the odds of CBP. To investigate whether benzene exposure may influence mRNA expression of p53 and p21 in benzene-exposed workers, we also chose 39 CBP workers, 38 occupationally benzene-exposure workers, and 37 nonexposure workers in the same region of China. PCR-restriction fragment length polymorphism technique was applied to detect polymorphisms of p53 (rs17878362, rs1042522, and rs1625895) and p21 (rs1801270 and rs1059234), and real-time PCR was applied to detect the quantity of gene mRNA expression. We found that p21 C98A variant genotypes (CA+AA) or C70T variant genotypes (CT+TT) were associated with decreased odds of CBP [odds ratio (OR), 0.51; 95% confidence interval (95% CI), 0.32-0.83, and OR, 0.53; 95% CI, 0.29-0.95, respectively. Further analysis showed the decreased odds of CBP in the subjects with p21 CC/AT diplotype (OR, 0.51; 95% CI, 0.30-0.85). In addition, p53 mRNA expression of CBP workers or benzene-exposure workers was significantly lower than that of nonexposure workers. Although these results require confirmation and extension, our results show that polymorphisms in p21 may be protective against the risk of CBP in the Chinese occupational population. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1821–8)

Studies on the relationships between inflammatory pathway genes and lung cancer risk have not included African-Americans and have only included a handful of genes. In a population-based case-control study on 198 African-American and 744 Caucasian women, we examined the association between 70 cytokine and cytokine receptor single-nucleotide polymorphisms (SNPs) and risk of non–small cell lung cancer (NSCLC). Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals in a dominant model adjusting for major risk factors for lung cancer. Separate analyses were conducted by race and by smoking history and history of chronic obstructive pulmonary disease among Caucasians. Random forest analysis was conducted by race. On logistic regression analysis, IL6 (interleukin 6), IL7R, IL15, TNF (tumor necrosis factor), and IL10 SNP were associated with risk of non–small cell lung cancer among African-Americans; IL7R and IL10 SNPs were also associated with risk of lung cancer among Caucasians. Although random forest analysis showed IL7R and IL10 SNPs as being associated with risk for lung cancer among African-Americans, it also identified TNFRSF10A SNP as an important predictor. On random forest analysis, an IL1A SNP was identified as an important predictor of lung cancer among Caucasian women. Inflammatory SNPs differentially predicted risk for NSCLC according to race, as well as based on smoking history and history of chronic obstructive pulmonary disease among Caucasian women. Pathway analysis results are presented. Inflammatory pathway genotypes may serve to define a high risk group; further exploration of these genes in minority populations is warranted. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1829–40)

There is some evidence that oxidative stress plays a role in lead-induced toxicity. Mechanisms for dealing with oxidative stress may be of particular relevance in the brain given the high rate of oxygen metabolism. Using a hospital-based case-control study, we investigated the role of oxidative stress in the potential carcinogenicity of lead through examination of effect modification of the association between occupational lead exposure and brain tumors by single nucleotide polymorphisms in genes with functions related to oxidative stress. The study included 362 patients with glioma (176 of which had glioblastoma multiforme), 134 patients with meningioma, and 494 controls. Lead exposure was estimated by expert review of detailed job history data for each participant. We evaluated effect modification with 142 single nucleotide polymorphisms using likelihood ratio tests that compared nested unconditional logistic regression models that did and did not include a cross-product term for cumulative lead exposure and genotype. When the analyses were restricted to cases with glioblastoma multiforme, RAC2 rs2239774 and two highly correlated GPX1 polymorphisms (rs1050450 and rs18006688) were found to significantly modify the association with lead exposure (P ≤ 0.05) after adjustment for multiple comparisons. Furthermore, the same GPX1 polymorphisms and XDH rs7574920 were found to significantly modify the association between cumulative lead exposure and meningioma. Although the results of this study provide some evidence that lead may cause glioblastoma multiforme and meningioma through mechanisms related to oxidative damage, the results must be confirmed in other populations. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1841–8)

Energy balance and the AKT pathway are important in colorectal cancer development and regulate p27 (cyclin-dependent kinase inhibitor-1B/CDKN1B/KIP1), which plays a role in preventing cell cycle progression. However, little is known on the clinical outcome or prognostic significance of p27 alterations in relation to patient body mass index (BMI). Among 630 colon cancers (stage I-IV) in two prospective cohort studies, we detected p27 alterations (cytoplasmic p27 localization or p27 loss) in 500 tumors (79%) by immunohistochemistry. The remaining 130 (21%) tumors were "p27-nuclear+." Cox proportional hazard models computed hazard ratios (HR) of deaths, adjusted for patient and tumoral characteristics, including p53, p21, cyclin D1, KRAS, BRAF, PIK3CA, cyclooxygenase-2, fatty acid synthase (FASN), β-catenin, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and long interspersed nucleotide element-1 (LINE-1) hypomethylation. Compared with p27-nuclear+ patients, p27-altered patients experienced low colon cancer–specific [adjusted HR, 0.63; 95% confidence interval (95% CI), 0.42-0.94] and overall mortality (adjusted HR, 0.70; 95% CI, 0.51-0.95), independent of FASN, MSI, CIMP, LINE-1 methylation, and other potential confounders. The effect of p27 alteration on overall mortality significantly differed by BMI (P_interaction = 0.013); adjusted HR (p27-altered versus p27-nuclear+ tumors) was 0.28 (95% CI, 0.13-0.59) for BMI ≥30 kg/m², 0.67 (95% CI, 0.40-1.14) for BMI 25 to 29 kg/m², and 0.91 (95% CI, 0.57-1.46) for BMI <25 kg/m². Obesity was associated with inferior overall survival among p27-nuclear+ cases (adjusted HR, 3.07; 95% CI, 1.49-6.32; versus nonobese cases), but not among p27-altered cases (adjusted HR, 1.08). In conclusion, p27 alterations in colon cancer are associated with superior prognosis. Adverse prognostic effect of obesity seems limited to patients with nuclear p27 expression, suggesting a host-tumor interaction. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1849–58)

An understanding of factors associated with prostate cancer (PCa) mortality is increasingly important given the biological heterogeneity of disease. Previous studies have shown that genetic variation in the Toll-like receptor (TLR) signaling pathway is associated with PCa incidence, but any role in progression and mortality is unclear. Among 1,252 PCa cases from the Cancer Prostate in Sweden study, we conducted time-to-event analyses of PCa mortality for 99 individual tagging SNPs and haploytpes from 20 genes in the TLR pathway. Cox proportional hazards models were used to estimate hazard ratios (HR) and 99% confidence intervals (99% CI). Global P values were estimated from a likelihood ratio test. During a median follow-up of 5.1 years, 191 PCa deaths occurred. Controlling for age and geographic location, two polymorphisms were statistically significantly associated with PCa mortality (P < 0.01). Compared with homozygous wild-type carriers of the TLR-9 polymorphism (rs187084), the HR (99% CI) was 1.57 (1.02, 2.41) for heterozygotes and 1.02 (0.57, 1.84) for rare homozygotes (P = 0.009). For a MIC-1 SNP (rs1227732), the HR comparing carriers of at least one copy of the minor allele to wild-type homozygotes was 0.54 (99% CI: 0.34, 0.87). Only the MIC-1 SNP remained significant after additional adjustment for treatment. No significant associations were observed for common haplotypes and PCa mortality. This study highlights the importance of studies of PCa mortality because risk factors for incidence and mortality may differ. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1859–63)

Background: Gene amplification leading to overexpression is a common event in breast tumors that is linked to tumor development and progression. The 17q23 region is amplified in >40% of breast tumors and contains several candidate oncogenes. Because common genetic variation in several oncogenes has been associated with cancer risk, we assessed the relevance of common variants in the 17q23 candidate oncogenes to breast cancer.

Methods: We investigated 60 polymorphisms in the TUBD1, SEPT4, PRKCA, TBX2, TBX4, TEX14, TLK2, YPEL2, and PPM1E genes from this amplicon for association with breast cancer risk among 798 Caucasian breast cancer cases and 843 unaffected Caucasian controls from the Mayo Clinic.

Results: Eight polymorphisms in PRKCA, TBX4, TLK2, and YPEL2 displayed significant dose-response associations with breast cancer risk (P_trend < 0.05). Of these, PRKCA rs7342847 and TLK2 rs2245092 and rs733025 were also associated with hormone receptor–positive breast cancer: PRKCA rs7342847 (odds ratio, 0.7; 95% confidence interval, 0.6-0.9; P_trend = 0.002) and TLK2 rs733025 and rs2245092 (both: odds ratio, 0.8; 95% confidence interval, 0.7-1.0; P_trend = 0.03). Interactions between SEPT4 rs758377 and TEX14 rs302864 (P_interaction = 0.0003) and between TLK2 rs733025 and YPEL2 rs16943468 (P_interaction = 0.05) for risk of breast cancer were also observed.

Conclusion: These findings suggest that single polymorphisms and combinations of polymorphisms within candidate oncogenes from the 17q23 amplicon may influence risk of breast cancer overall and possibly specific molecular subtypes of breast tumors. The findings are discussed within the context of the results from two independent data sets. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1864–8)

To estimate the prostate cancer risk conferred by individual single nucleotide polymorphisms (SNPs), SNP-SNP interactions, and/or cumulative SNP effects, we evaluated the association between prostate cancer risk and the genetic variants of 12 key genes within the steroid hormone pathway (CYP17, HSD17B3, ESR1, SRD5A2, HSD3B1, HSD3B2, CYP19, CYP1A1, CYP1B1, CYP3A4, CYP27B1, and CYP24A1). A total of 116 tagged SNPs covering the group of genes were analyzed in 2,452 samples (886 cases and 1,566 controls) in three ethnic/racial groups. Several SNPs within CYP19 were significantly associated with prostate cancer in all three ethnicities (P = 0.001-0.009). Genetic variants within HSD3B2 and CYP24A1 conferred increased risk of prostate cancer in non-Hispanic or Hispanic Caucasians. A significant gene-dosage effect for increasing numbers of potential high-risk genotypes was found in non-Hispanic and Hispanic Caucasians. Higher-order interactions showed a seven-SNP interaction involving HSD17B3, CYP19, and CYP24A1 in Hispanic Caucasians (P = 0.001). In African Americans, a 10-locus model, with SNPs located within SRD5A2, HSD17B3, CYP17, CYP27B1, CYP19, and CYP24A1, showed a significant interaction (P = 0.014). In non-Hispanic Caucasians, an interaction of four SNPs in HSD3B2, HSD17B3, and CYP19 was found (P < 0.001). These data are consistent with a polygenic model of prostate cancer, indicating that multiple interacting genes of the steroid hormone pathway confer increased risk of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1869–80)

Background: Because of its nutrients and anabolic hormones, cow's milk may promote height growth, which in turn has been related to breast cancer risk. We prospectively investigated associations between dairy intakes and height growth.

Methods: A cohort of 5,101 girls from throughout the United States completed annual surveys (1996-2001, 2003), providing height, weight, and past-year diet. At baseline, all were premenarchal, ages 9 years and above, with no serious medical conditions. We studied three outcomes: annual height growth, peak growth velocity, and adult height. Multivariate models estimated the effects of milk, cheese, yogurt, and energy on subsequent growth, adjusted for race/ethnicity, age, prior height, and body mass index. Other models studied fats and proteins.

Results: Premenarchal girls who drank >3 servings per day of milk grew 0.11 in. (P = 0.02) more the following year than girls consuming <1 serving per day. Yogurt (+0.13 in./cup; P = 0.02), but not cheese or total calories, predicted height growth. In a separate model, dairy protein (+0.034 in./10 g; P < 0.001) predicted height growth. Larger peak velocities were seen among girls reporting, at baseline, more milk (>3 glasses per day versus <1; +0.14 in., P = 0.01), more yogurt (+0.17 in./cup, P = 0.02), and, in a separate model, more dairy protein (+0.039 in./10 g; P = 0.003). Baseline milk and dairy protein predicted taller adults. Dairy protein was more important than dairy fat, for all outcomes. Nondairy animal protein and vegetable protein were never significant, nor were nondairy animal fat and vegetable fat.

Conclusion: Of the foods/nutrients studied, dairy protein had the strongest association with height growth. These findings suggest that a factor in the nonlipid phase of milk, but not protein itself, has growth-promoting action in girls. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1881–7)

We previously reported that fecal cyclooxygenase 2 (COX-2) mRNA assay, detecting COX-2 mRNA in feces, is useful for identifying subjects with colorectal cancer (CRC). To further improve the sensitivity, we evaluated the usefulness of the combination of COX-2 mRNA and matrix metalloproteinase 7 (MMP-7) mRNA assays as a marker of CRC. The study cohort included 62 patients with CRC and 29 control patients without colorectal neoplasia. RNA was isolated from routinely collected fecal samples. The expression levels of COX-2 and MMP-7 mRNAs were determined by nested reverse transcription-PCR. PCR conditions were optimized where the specificity of fecal COX-2 and MMP-7 mRNA assay result in 100%. The sensitivity of each fecal assay was 87% [95% confidence interval (95% CI), 76-94%] and 65% (95% CI, 51-76%) for CRC, respectively. The sensitivity of fecal RNA test (either marker being positive) was high for CRC (90%; 95% CI, 80-96%). The sensitivity of the fecal RNA test was also high (93%; 95% CI, 80-98%) in patients with stage I or II who are often cured by surgical resection. The fecal RNA test using COX-2 and MMP-7 mRNAs improved the sensitivity to detect CRC without decreasing the specificity. These results suggest that the fecal RNA test would be a promising approach for CRC screening, although larger clinical investigations are indicated. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1888–93)

Hepatitis B (HBV) and hepatitis C (HCV) viral infections are the most important risk factors for hepatocellular carcinoma (HCC), which is responsible for 17.5% of cancer deaths in Korea. The objectives of this study were to identify demographic characteristics that may affect hepatitis carriers' awareness of their infection status, and to assess whether health-related behaviors differed by awareness of the infection. Among 18,636 persons who were recruited from a cancer screenee cohort, 904 were HBV carriers and 146 were HCV carriers. Among the HBV carriers, 74.2% were aware of their infection status. Higher education (odds ratio, 1.8; college versus middle school or less), family history of liver cancer or disease, and marriage were associated with awareness of HBV infection status. Participants who were aware of their HBV carrier status were more likely to be former smokers or drinkers than those who were not aware of their status. Only 34.9% of HCV carriers were aware of their HCV infection status. No demographic characteristics were related to awareness of HCV infection status among HCV carriers. However, HCV carriers who were aware of their infection status were more likely to be former drinkers (odds ratio, 9.2; 95% confidence interval, 1.8-47.2). In conclusion, two thirds of HCV carriers and one fourth of HBV carriers in this study population were not aware of their infection status, and awareness of hepatitis infection status was significantly associated with other risk behaviors, such as alcohol consumption and cigarette smoking. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1894–8)

We previously described frequent overexpression of Sam-pointed domain containing Ets transcription factor (SPDEF), also known as PDEF, in human breast cancer, and suggested a role for this transcription factor in breast tumor progression. To seek evidence in support of this hypothesis, the MCF-12A breast epithelial cell line was transfected with an SPDEF expression plasmid or with control vector plasmid and the transfected cells tested for their tumorigenic growth in vivo. The data showed that SPDEF expression in MCF-12A cells induced accelerated tumor growth in severe combined immune deficient mice compared with vector-transfected MCF-12A cells. Furthermore, Gene Expression Omnibus and Oncomine databases were mined to determine any correlation between SPDEF expression levels and clinical outcome. High SPDEF expression correlated with poor overall survival of patients with estrogen receptor+ breast cancer, in three independent data sets. In contrast, little correlation was observed between SPDEF expression and cancer relapse or remote metastases. SPDEF expression was further found to be restricted to tumors arising in the luminal epithelial lineage including estrogen receptor+ luminal subtype breast tumors, Her2/neu-positive tumors, and apocrine carcinomas. In contrast, little SPDEF expression was found in the basal subtype of breast tumors. Based on these results, we hypothesize that SPDEF has a function in the specification of the progenitor cells of the luminal epithelial lineage that become targets of oncogenesis in luminal breast cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1899–903)

Purpose: Circulating tumor cells (CTC) have been recently accepted by the Food and Drug Administration of the United States as a prognostic tool in advanced prostate cancer. However, a number of questions remain about the use of the test. The optimal clinical cut-off has never been determined. Also, the predictive value of CTCs in the setting of low-burden advanced prostate cancer has not been evaluated. Herein we describe our experience with the CellSearch method of CTC enumeration.

Experimental Design: CTCs enumerated from 100 patients with castration-resistant prostate cancer were correlated with clinicopathologic characteristics and conventional biomarkers, such as prostate-specific antigen and lactate dehydrogenase. Patients received ongoing medical oncologic follow-up for up to 26 months, and overall survival status was documented.

Results: Forty-nine of the patients (49%) were alive at the end of the study. CTC counts correlate well with overall survival (P < 0.001) but are also tightly interrelated to other biomarkers. Threshold analysis identified 4 CTC/7.5 cc (compared with the approved value of 5) as an optimal cut-off value with respect to correlation with survival outcomes as well as predictive of metastatic disease. Univariate analysis confirmed a tight interrelationship between cut-off CTC values and biomarkers. Multivariate analysis with bootstrap sampling validation identified lactate dehydrogenase (P = 0.002) and CTCs (P = 0.001) as independently prognostically significant.

Conclusions: Baseline CTC values provide important prognostic information and specific prediction of metastatic disease. Their presence correlates with classic biomarkers. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1904–13)

Changes in glycosylation, most notably fucosylation, have been associated with the development of hepatocellular carcinoma (HCC). In this report, the levels of fucosylated kininogen (Fc-Kin) and fucosylated -1-antitrypsin were analyzed individually and in combination with the currently used marker, -fetoprotein, and a previously identified biomarker, Golgi protein 73 (GP73), for the ability to distinguish between a diagnosis of cirrhosis and HCC. This analysis was done on serum from 113 patients with cirrhosis and 164 serum samples from patients with cirrhosis plus HCC. The levels of Fc-Kin and fucosylated -1-antitrypsin were significantly higher in patients with HCC compared with those with cirrhosis (P < 0.0001). Greatest performance was achieved through the combination of Fc-Kin, -fetoprotein, and GP73, giving an optimal sensitivity of 95%, a specificity of 70%, and an area under the receiver operating characteristic of 0.94. In conclusion, the altered glycosylation of serum glycoproteins can act as potential biomarkers of primary HCC when used independently or in combination with other markers of HCC. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1914–21)

IGF2R has been proposed to be a tumor suppressor gene given its antagonist role on cellular growth and evidence of loss of heterozygosity in several cancers, including breast cancer. To investigate whether inherited differences in potentially functional IGF2R variants influence the risk of breast cancer, we sequenced 46 exons of IGF2R to identify novel missense single-nucleotide polymorphisms (SNP) and tested 12 missense SNPs for their associations with breast cancer risk among 1,614 breast cancer cases and 1,960 controls from the Multiethnic Cohort. None of these missense SNPs were significantly associated with breast cancer risk. Our findings provide no evidence that missense SNPs in IGF2R influence breast cancer susceptibility.(Cancer Epidemiol Biomarkers Prev 2009;18(6):1922–4)

Vitamin D has antiproliferative, antiangiogenic, and apoptotic properties. There is some evidence supporting an association between vitamin D–related gene variants and prostate cancer risk. We report results from this population-based case-control study of genes encoding for the vitamin D receptor (VDR), the vitamin D activating enzyme 1--hydroxylase (CYP27B1), and deactivating enzyme 24-hydroxylase (CYP24A1). Forty-eight tagging single nucleotide polymorphisms (tagSNP) were analyzed in 827 incident prostate cancer cases diagnosed from 2002 to 2005, and in 787 age-matched controls. Contrary to some earlier studies, we found no strong evidence of altered risk of developing prostate cancer overall or within clinical measures of tumor aggressiveness for any of the tagSNPs when they were assessed individually or in haplotypes. (Cancer Epidemiol NBiomarkers Prev 2009;18(6):1929–33)

SMAD7 and GREM1 are signaling components on the transforming growth factor-β pathway, which regulates normal mammary gland development and has been implicated in breast tumor invasion and metastasis. Three variants within SMAD7 and two variants in CRAC1 (a colorectal cancer–associated region on chromosome 15 in which GREM1 is located) have been associated with colorectal cancer risks [odds ratios (OR), 0.85-1.26; all P < 10^–7]. We genotyped these five variants in a series of 1,267 bilateral breast cancer cases and 900 controls to determine whether they are associated with breast as well as colorectal cancer risk. None of these single nucleotide polymorphisms were associated with breast cancer risk in our study and the 95% confidence limits of our data, pooled with data from the Cancer Genetic Markers of Susceptibility study, exclude per allele ORs of <0.94 or >1.08. One or more of these variants may be associated with a very small OR for breast cancer, but our data suggest that the effects of these alleles are cancer site–specific. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1934–6)

Thiazolidinediones (TZD) have been shown to down-regulate prostate-specific antigen (PSA) levels in prostate cancer cell lines and decrease PSA velocity among prostate cancer patients; however, the effect of TZDs on serum PSA levels among men with diabetes at risk for prostate cancer is unknown. We conducted a retrospective cohort study of veterans receiving care for diabetes between 1999 and 2005 to determine if TZD use affects PSA levels in veterans at risk for prostate cancer. Eligible patients were male, ≥45 years old, taking at least one oral antidiabetic medication, and with two or more recorded PSA values. Patients with a prior history of prostate cancer or prostatectomy were excluded. Of the 13,791 patients included in the adjusted analysis, 2,016 (14.6%) were prescribed a TZD. No effect of cumulative TZD dose on change in PSA was detected (P = 0.26). Increased TZD exposure was not associated with a change in PSA, suggesting that TZD treatment for diabetes is unlikely to affect prostate cancer detection. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1937–8)

Background: Acrylamide is a probable human carcinogen that can be formed in foods prepared at high temperatures. Whereas evidence indicates that acrylamide causes cancer in laboratory animals, epidemiologic data on dietary acrylamide intake in relation to cancer risk are limited and mainly null. We examined the association between dietary acrylamide intake and risk of prostate cancer in a cohort of men.

Methods: The Cohort of Swedish Men is a population-based prospective study of 45,306 men who were cancer-free and completed a food frequency questionnaire at enrollment in 1997. Cox proportional hazards models were used to estimate relative risks adjusted for potential confounders.

Results: During a mean follow-up of 9.1 years, we ascertained 2,696 incident cases of prostate cancer. We observed no association between acrylamide intake and risk of prostate cancer. Compared with the lowest quintile of acrylamide intake (mean, 23.7 µg/d), the multivariable relative risks (95% confidence interval) for the highest quintile (mean, 49.8 µg/d) were 0.88 (0.70-1.09) for total prostate cancer, 1.07 (0.87-1.32) for localized prostate cancer (n = 1,088), and 0.98 (0.78-1.22) for advanced prostate cancer (n = 951).

Conclusions: Results from this prospective study provide no evidence that dietary acrylamide in amounts typically consumed by Swedish men is associated with risk of prostate cancer.(Cancer Epidemiol Biomarkers Prev 2009;18(6):1939–41)