Common genetic polymorphisms modify the effect of smoking on absolute risk of bladder cancer
| Autor: | Margaret R. Karagas, Molly Schwenn, Demetrius Albanes, Kevin B. Jacobs, W. R. Diver, Laurie Burdett, Debra T. Silverman, Montserrat Garcia-Closas, Michael J. Thun, Amanda Black, Nilanjan Chatterjee, Joseph F. Fraumeni, Josep Lloreta, Stephen J. Chanock, Yi-Ping Fu, Ludmila Prokunina-Olsson, Alison Johnson, Alan R. Schned, David J. Hunter, Núria Malats, Wei Tang, Manolis Kogevinas, Nathaniel Rothman, Consol Serra, Adonina Tardón, Zhaoming Wang, Summer S. Han, Neil E. Caporaso, Mark P. Purdue, Jarmo Virtamo, Gerald L. Andriole, Alfredo Carrato, Eric J. Jacobs, Jonine D. Figueroa, Immaculata De Vivo, Dalsu Baris, Amy Hutchinson, Maria Teresa Landi, Susan M. Gapstur, Sapna Sharma, Robert L. Grubb, Stephanie J. Weinstein, Meredith Yeager, Reina García-Closas |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Genotype Genome-wide association study Article Young Adult 03 medical and health sciences 0302 clinical medicine Risk Factors Internal medicine medicine Humans Prospective Studies Risk factor Young adult Prospective cohort study Aged 030304 developmental biology Aged 80 and over 0303 health sciences Polymorphism Genetic Bladder cancer business.industry Smoking Case-control study Absolute risk reduction Middle Aged Prognosis medicine.disease 3. Good health Surgery Urinary Bladder Neoplasms Oncology Quartile Case-Control Studies 030220 oncology & carcinogenesis Female Gene-Environment Interaction business Carcinoma in Situ Follow-Up Studies Genome-Wide Association Study |
| Zdroj: | Cancer Research; Vol 73 |
| Popis: | 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 (Padditive = 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. Cancer Res; 73(7); 2211–20. ©2012 AACR. |
| Databáze: | OpenAIRE |
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