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Common genetic polymorphisms modify the effect of smoking on absolute risk of bladder cancer.


ABSTRACT: Bladder cancer results from the combined effects of environmental and genetic factors, smoking being the strongest risk factor. Evaluating absolute risks resulting from the joint effects of smoking and genetic factors is critical to assess the public health relevance of genetic information. Analyses included up to 3,942 cases and 5,680 controls of European background in seven studies. We tested for multiplicative and additive interactions between smoking and 12 susceptibility loci, individually and combined as a polygenic risk score (PRS). Thirty-year absolute risks and risk differences by levels of the PRS were estimated for U.S. males aged 50 years. Six of 12 variants showed significant additive gene-environment interactions, most notably NAT2 (P = 7 × 10(-4)) and UGT1A6 (P = 8 × 10(-4)). The 30-year absolute risk of bladder cancer in U.S. males was 6.2% for all current smokers. This risk ranged from 2.9% for current smokers in the lowest quartile of the PRS to 9.9% for current smokers in the upper quartile. Risk difference estimates indicated that 8,200 cases would be prevented if elimination of smoking occurred in 100,000 men in the upper PRS quartile compared with 2,000 cases prevented by a similar effort in the lowest PRS quartile (P(additive) = 1 × 10(-4)). Thus, the potential impact of eliminating smoking on the number of bladder cancer cases prevented is larger for individuals at higher than lower genetic risk. Our findings could have implications for targeted prevention strategies. However, other smoking-related diseases, as well as practical and ethical considerations, need to be considered before any recommendations could be made.

SUBMITTER: Garcia-Closas M 

PROVIDER: S-EPMC3688270 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Common genetic polymorphisms modify the effect of smoking on absolute risk of bladder cancer.

Garcia-Closas Montserrat M   Rothman Nathaniel N   Figueroa Jonine D JD   Prokunina-Olsson Ludmila L   Han Summer S SS   Baris Dalsu D   Jacobs Eric J EJ   Malats Nuria N   De Vivo Immaculata I   Albanes Demetrius D   Purdue Mark P MP   Sharma Sapna S   Fu Yi-Ping YP   Kogevinas Manolis M   Wang Zhaoming Z   Tang Wei W   Tardón Adonina A   Serra Consol C   Carrato Alfredo A   García-Closas Reina R   Lloreta Josep J   Johnson Alison A   Schwenn Molly M   Karagas Margaret R MR   Schned Alan A   Andriole Gerald G   Grubb Robert R   Black Amanda A   Gapstur Susan M SM   Thun Michael M   Diver William Ryan WR   Weinstein Stephanie J SJ   Virtamo Jarmo J   Hunter David J DJ   Caporaso Neil N   Landi Maria Teresa MT   Hutchinson Amy A   Burdett Laurie L   Jacobs Kevin B KB   Yeager Meredith M   Fraumeni Joseph F JF   Chanock Stephen J SJ   Silverman Debra T DT   Chatterjee Nilanjan N  

Cancer research 20130327 7


Bladder cancer results from the combined effects of environmental and genetic factors, smoking being the strongest risk factor. Evaluating absolute risks resulting from the joint effects of smoking and genetic factors is critical to assess the public health relevance of genetic information. Analyses included up to 3,942 cases and 5,680 controls of European background in seven studies. We tested for multiplicative and additive interactions between smoking and 12 susceptibility loci, individually  ...[more]

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