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Modification of Occupational Exposures on Bladder Cancer Risk by Common Genetic Polymorphisms.

ABSTRACT: Few studies have demonstrated gene/environment interactions in cancer research. Using data on high-risk occupations for 2258 case patients and 2410 control patients from two bladder cancer studies, we observed that three of 16 known or candidate bladder cancer susceptibility variants displayed statistically significant and consistent evidence of additive interactions; specifically, the GSTM1 deletion polymorphism (P interaction ? .001), rs11892031 (UGT1A, P interaction = .01), and rs798766 (TMEM129-TACC3-FGFR3, P interaction = .03). There was limited evidence for multiplicative interactions. When we examined detailed data on a prevalent occupational exposure associated with increased bladder cancer risk, straight metalworking fluids, we also observed statistically significant additive interaction for rs798766 (TMEM129-TACC3-FGFR3, P interaction = .02), with the interaction more apparent in patients with tumors positive for FGFR3 expression. All statistical tests were two-sided. The interaction we observed for rs798766 (TMEM129-TACC3-FGFR3) with specific exposure to straight metalworking fluids illustrates the value of integrating germline genetic variation, environmental exposures, and tumor marker data to provide insight into the mechanisms of bladder carcinogenesis.

SUBMITTER: Figueroa JD

PROVIDER: S-EPMC4675099 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Modification of Occupational Exposures on Bladder Cancer Risk by Common Genetic Polymorphisms.

Figueroa Jonine D JD Koutros Stella S Colt Joanne S JS Kogevinas Manolis M Garcia-Closas Montserrat M Real Francisco X FX Friesen Melissa C MC Baris Dalsu D Stewart Patricia P Schwenn Molly M Johnson Alison A Karagas Margaret R MR Armenti Karla R KR Moore Lee E LE Schned Alan A Lenz Petra P Prokunina-Olsson Ludmila L Banday A Rouf AR Paquin Ashley A Ylaya Kris K Chung Joon-Yong JY Hewitt Stephen M SM Nickerson Michael L ML Tardón Adonina A Serra Consol C Carrato Alfredo A García-Closas Reina R Lloreta Josep J Malats Núria N Fraumeni Joseph F JF Chanock Stephen J SJ Chatterjee Nilanjan N Rothman Nathaniel N Silverman Debra T DT

Journal of the National Cancer Institute 20150914 11

Few studies have demonstrated gene/environment interactions in cancer research. Using data on high-risk occupations for 2258 case patients and 2410 control patients from two bladder cancer studies, we observed that three of 16 known or candidate bladder cancer susceptibility variants displayed statistically significant and consistent evidence of additive interactions; specifically, the GSTM1 deletion polymorphism (P interaction ≤ .001), rs11892031 (UGT1A, P interaction = .01), and rs798766 (TMEM ...[more]

PMID: 26374428

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Project description:BackgroundBy-products are formed when disinfectants react with organic matter in source water. The most common class of disinfection by-products, trihalomethanes (THMs), have been linked to bladder cancer. Several studies have shown exposure-response associations with THMs in drinking water and bladder cancer risk. Few epidemiologic studies have evaluated gene-environment interactions for total THMs (TTHMs) with known bladder cancer susceptibility variants.ObjectivesIn this study, we investigated the combined effect on bladder cancer risk contributed by TTHMs, bladder cancer susceptibility variants identified through genome-wide association studies, and variants in several candidate genes.MethodsWe analyzed data from two large case-control studies-the New England Bladder Cancer Study (n/n=989 cases/1,162 controls), a population-based study, and the Spanish Bladder Cancer Study (n/n=706 cases/772 controls), a hospital-based study. Because of differences in exposure distributions and metrics, we estimated effects of THMs and genetic variants within each study separately using adjusted logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CI) with and without interaction terms, and then combined the results using meta-analysis.ResultsOf the 16 loci showing strong evidence of association with bladder cancer, rs907611 at 11p15.5 [leukocyte-specific protein 1 (LSP1 region)] showed the strongest associations in the highest exposure category in each study, with evidence of interaction in both studies and in meta-analysis. In the highest exposure category, we observed OR=1.66 (95% CI: 1.17, 2.34, p-trend=0.005) for those with the rs907611-GG genotype and p-interaction=0.02. No other genetic variants tested showed consistent evidence of interaction.DiscussionWe found novel suggestive evidence for a multiplicative interaction between a putative bladder carcinogen, TTHMs, and genotypes of rs907611. Given the ubiquitous exposure to THMs, further work is needed to replicate and extend this finding and to understand potential molecular mechanisms. https://doi.org/10.1289/EHP9895.

Project description:ObjectivesUp to 10% of Bladder Cancers may arise following occupational exposure to carcinogens. We hypothesised that different cancer phenotypes reflected different patterns of occupational exposure.MethodsConsecutive participants, with bladder cancer, self-completed a structured questionnaire detailing employment, tasks, exposures, smoking, lifestyle and family history. Our primary outcome was association between cancer phenotype and occupational details.ResultsWe collected questionnaires from 536 patients, of whom 454 (85%) participants (352 men and 102 women) were included. Women were less likely to be smokers (68% vs. 81% Chi sq. p<0.001), but more likely than men to inhale environmental tobacco smoke at home (82% vs. 74% p = 0.08) and use hair dye (56% vs. 3%, p<0.001). Contact with potential carcinogens occurred in 282 (62%) participants (mean 3.1 per worker (range 0-14)). High-grade cancer was more common than low-grade disease in workers from the steel, foundry, metal, engineering and transport industries (p<0.05), and in workers exposed to crack detection dyes, chromium, coal/oil/gas by-products, diesel fumes/fuel/aircraft fuel and solvents (such as trichloroethylene). Higher staged cancers were frequent in workers exposed to Chromium, coal products and diesel exhaust fumes/fuel (p<0.05). Various workers (e.g. exposed to diesel fuels or fumes (Cox, HR 1.97 (95% CI 1.31-2.98) p = 0.001), employed in a garage (HR 2.19 (95% CI 1.31-3.63) p = 0.001), undertaking plumbing/gas fitting/ventilation (HR 2.15 (95% CI 1.15-4.01) p = 0.017), undertaking welding (HR 1.85 (95% CI 1.24-2.77) p = 0.003) and exposed to welding materials (HR 1.92 (95% CI 1.27-2.91) p = 0.002)) were more likely to have disease progression and receive radical treatment than others. Fewer than expected deaths were seen in healthcare workers (HR 0.17 (95% CI 0.04-0.70) p = 0.014).ConclusionsWe identified multiple occupational tasks and contacts associated with bladder cancer. There were some associations with phenotype, although our study design precludes robust assessment.

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Modification of Occupational Exposures on Bladder Cancer Risk by Common Genetic Polymorphisms.

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Modification of Occupational Exposures on Bladder Cancer Risk by Common Genetic Polymorphisms.

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