Journal
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
Volume 107, Issue 11, Pages -Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/jnci/djv223
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Funding
- Intramural Research Program of the National Institutes of Health
- Division of Cancer Epidemiology and Genetics, National Cancer Institute
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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.
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