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Silver Spring, MD, United States

Lenz P.,U.S. National Cancer Institute | Pfeiffer R.,U.S. National Cancer Institute | Baris D.,U.S. National Cancer Institute | Takikita M.,U.S. National Cancer Institute | And 8 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2012

Background: Cell-cycle proteins are important predictive markers in urothelial carcinoma but may also exhibit exposure-specific heterogeneity. Methods: Tumor tissue from 491 bladder cancer cases enrolled in the Maine and Vermont component of the New England Bladder Cancer Study was assembled as tissue microarrays and examined for aberrant expression of p53, p63, p16, cyclin D1, Rb, and Ki-67. The association between expression and histopathology, demographics, and cigarette smoking was examined using c2 tests, multivariable Poisson, and multinomial regression models. Results: We found that overexpression of p53 and Ki-67 was associated with high-stage/grade tumors [relative risk (RR), 1.26; Ptrend = 0.003; and RR, 3.21; P trend < 0.0001, respectively], whereas expression of p63 and p16 was decreased in high-stage/grade tumors (RR, 0.52; Ptrend < 0.0001; and RR, 0.88; Ptrend = 0.04, respectively). No significant aberrations of cell-cycle proteins were identified using various smoking variables and multiple statistical models. Conclusion: The results of this population-based study of histologically confirmed urothelial carcinomas show significant aberration of cell-cycle proteins p53, p63, p16, and Ki-67, but not Rb or cyclin D1. p53 showed the most significant heterogeneity with respect to tumor stage and grade, especially when stratified for different staining intensities using novel digital image analysis techniques. Our findings do not support that smoking modifies expression of cell-cycle proteins. Impact: Our study shows significant heterogeneity in the expression of key cell-cycle proteins that are associated with disease progression in bladder cancer. Further studies may lead to the identification of biomarkers and their multiplexed interactions as useful prognostic and therapeutic targets. ©2012 AACR.

Amaral A.F.S.,Genetic and Molecular Epidemiology Group | Porta M.,Autonomous University of Barcelona | Porta M.,CIBER ISCIII | Silverman D.T.,U.S. National Cancer Institute | And 13 more authors.
Gut | Year: 2012

Background and Aims: Knowledge on the aetiology of exocrine pancreatic cancer (EPC) is scant. The best established risk factor for EPC is tobacco smoking. Among other carcinogens, tobacco contains cadmium, a metal previously associated with an increased risk of EPC. This study evaluated the association between concentrations of trace elements in toenails and EPC risk. Methods: The study included 118 EPC cases and 399 hospital controls from eastern Spain. Levels of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. OR and 95% CI, adjusted for potential confounders, were calculated using logistic regression. Results: Significantly increased risks of EPC were observed among subjects whose concentrations of cadmium (OR 3.58, 95% CI 1.86 to 6.88; ptrend=5×10 -6), arsenic (OR 2.02, 95% CI 1.08 to 3.78; ptrend=0.009) and lead (OR 6.26, 95% CI 2.71 to 14.47; ptrend=3×10- 5) were in the highest quartile. High concentrations of selenium (OR 0.05, 95% CI 0.02 to 0.15; ptrend=8×10-11) and nickel (OR 0.27, 95% CI 0.12 to 0.59; ptrend=2×10-4) were inversely associated with the risk of EPC. Conclusion: Novel associations are reported of lead, nickel and selenium toenail concentrations with pancreas cancer risk. Furthermore, the results confirm previous associations with cadmium and arsenic. These novel findings, if replicated in independent studies, would point to an important role of trace elements in pancreatic carcinogenesis.

Brock K.E.,University of Sydney | Ke L.,University of Sydney | Gridley G.,U.S. National Cancer Institute | Chiu B.C.-H.,University of Chicago | And 5 more authors.
British Journal of Nutrition | Year: 2012

The association between renal cell cancer (RCC) and intake of fruit, vegetables and nutrients was examined in a population-based case-control study of 323 cases and 1827 controls; dietary intake was obtained using a mailed questionnaire. Cancer risks were estimated by OR and 95% CI, adjusting for age, sex, smoking, obesity, hypertension, proxy status, alcohol consumption and dietary fat intake and energy. Intake of vegetables was associated with a decreased risk of RCC (OR 0.5; 95% CI 0.3, 0.7; P trend=0.002), (top compared to the bottom quartile of intake). When intake of individual nutrients was investigated, vegetable fibre intake was associated with decreased risks (OR 0.4; 95% CI 0.2, 0.6; P<0.001), but this was not the case with fruit fibre (OR 0.7; 95% CI 0.4, 1.1) or grain fibre (OR 1.0; 95% CI 0.6, 1.5). β-Cryptoxanthin and lycopene were also associated with decreased risks, but when both were included in a mutually adjusted backwards stepwise regression model, only β-cryptoxanthin remained significant (OR 0.5; 95% CI 0.3, 0.8). When other micronutrients and types of fibre were investigated together, only vegetable fibre and β-cryptoxanthin had significant trends (P<0.01) (OR 0.6; 95% CI 0.3, 0.9) (OR 0.5; 95% CI 0.3, 0.9), respectively. These findings were stronger in those aged over 65 years (P interaction=0.001). Among non-smokers, low intake of cruciferous vegetables and fruit fibre was also associated with increased risk of RCC (P interaction=0.03); similar inverse associations were found for β-cryptoxanthin, lycopene and vitamin C. When nutrients were mutually adjusted by backwards regression in these subgroups, only β-cryptoxanthin remained associated with lower RCC risk. These findings deserve further investigation in ongoing prospective studies when sample size becomes sufficient. © 2011 The Authors.

Steinmaus C.,University of California at Berkeley | Steinmaus C.,U.S. Environmental Protection Agency | Ferreccio C.,University of Santiago de Chile | Acevedo J.,University of Santiago de Chile | And 15 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2014

Background: From 1958 to 1970, >100,000 people in northern Chile were exposed to a well-documented, distinct period of high drinking water arsenic concentrations. We previously reported ecological evidence suggesting that early-life exposure in this population resulted in increased mortality in adults from several outcomes, including lung and bladder cancer. Methods: We have now completed the first study ever assessing incident cancer cases after early-life arsenic exposure, and the first study on this topic with individual participant exposure and confounding factor data. Subjects included 221 lung and 160 bladder cancer cases diagnosed in northern Chile from 2007 to 2010, and 508 age and gender-matched controls. Results: ORs adjusted for age, sex, and smoking in those only exposed in early life to arsenic water concentrations of ≤110,110 to 800, and >800 μg/L were 1.00,1.88 [95% confidence interval (CI), 0.96-3.71], and 5.24 (3.05-9.00; Ptrend < 0.001) for lung cancer, and 1.00,2.94 (1.29-6.70), and 8.11 (4.31-15.25; Ptrend < 0.001) for bladder cancer. ORs were lower in those not exposed until adulthood. The highest category (>800 μg/L) involved exposures that started 49 to 52 years before, and ended 37 to 40 years before the cancer cases were diagnosed. Conclusion: Lung and bladder cancer incidence in adults was markedly increased following exposure to arsenic in early life, even up to 40 years after high exposures ceased. Such findings have not been identified before for any environmental exposure, and suggest that humans are extraordinarily susceptible to early-life arsenic exposure. Impact: Policies aimed at reducing early-life exposure may help reduce the long-term risks of arsenic-related disease. © 2014 American Association for Cancer Research. doi: 10.1158/1055-9965.EPI-14- 0059.

Amaral A.F.S.,Spanish National Cancer Research Center | Cantor K.P.,KP Cantor Environmental LLC | Silverman D.T.,U.S. National Cancer Institute | Malats N.,Spanish National Cancer Research Center
Cancer Epidemiology Biomarkers and Prevention | Year: 2010

Background: Selenium is considered to be an antioxidant, and its high levels have been inversely associated with cancer risk of several sites. This meta-analysis examined the relationship between levels of selenium measured in serum and toenails, and the risk of bladder cancer. Methods: A meta-analysis using data from seven published epidemiologic studies (three case-control, three nested case-control, one case-cohort) published before March 2010 was done to examine the association between levels of selenium and bladder cancer. Fixed and random effects analyses were done to calculate meta-odds ratio (mOR) and 95% confidence intervals (CI). Heterogeneity among studies was measured by the I2 statistic. Results: Overall, the risk of bladder cancer was inversely associated with elevated levels of selenium according to a random-effects model (mOR = 0.61; 95% CI, 0.42-0.87). The mORs were 0.95 (95% CI, 0.69-1.27) and 0.55 (95% CI, 0.32-0.95) among men and women, respectively. Sex, type of sample specimen, smoking status, and study design were found to be potential sources of heterogeneity. Conclusions: A significant protective effect of selenium, observed mainly among women, may result from gender-specific differences in its accumulation and excretion. The heterogeneity found among studies was mainly linked to the different biological sample specimens used to measure the selenium concentrations and the small size of the studies. Although these results suggest a protective effect of selenium for bladder cancer risk, additional large studies are warranted to support these preliminary evidence. Impact: The present results suggest a beneficial effect of high selenium intake for bladder cancer risk. ©2010 AACR.

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