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

作者：Figueroa Jonine D^*; Koutros Stella; Colt Joanne S; Kogevinas Manolis; Garcia Closas Montserrat; Real Francisco X; Friesen Melissa C; Baris Dalsu; Stewart Patricia; Schwenn Molly; Johnson Alison; Karagas Margaret R; Armenti Karla R; Moore Lee E; Schned Alan; Lenz Petra; Prokunina Olsson Ludmila; Banday A Rouf; Paquin Ashley; Ylaya Kris; Chung Joon Yong; Hewitt Stephen M; Nickerson Michael L; Tardon Adonina; Serra Consol; Carrato Alfredo; Garcia Closas Reina

来源：JNCI-Journal of the National Cancer Institute, 2015, 107(11): djv223.

DOI：10.1093/jnci/djv223

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.

• 出版日期2015-11
• 单位NIH; 河北医科大学