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

机译:常见遗传多态性对职业性膀胱癌风险暴露的影响

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摘要

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.
机译:很少有研究证明癌症研究中的基因/环境相互作用。使用来自两项膀胱癌研究的2258例患者和2410例对照患者的高风险职业数据,我们观察到16种已知或候选膀胱癌易感性变体中的3种在统计学上具有显着性且一致的加性相互作用证据。具体来说,是GSTM1缺失多态性(P相互作用≤.001),rs11892031(UGT1A,P相互作用= .01)和rs798766(TMEM129-TACC3-FGFR3,P相互作用= .03)。乘法相互作用的证据有限。当我们检查有关与膀胱癌风险增加,纯金属加工液相关的普遍职业暴露的详细数据时,我们还观察到rs798766具有统计学意义的显着加性相互作用(TMEM129-TACC3-FGFR3,P相互作用= .02),而在FGFR3表达阳性的肿瘤患者。所有统计检验都是双面的。我们观察到的rs798766(TMEM129-TACC3-FGFR3)与直接暴露于纯金属加工液中的相互作用说明了整合种系遗传变异,环境暴露和肿瘤标志物数据的价值,以提供对膀胱癌发生机理的了解。

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