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Lookup NU author(s): Professor Caroline Relton
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Backgrounds: Multiple polymorphisms affecting smoking behavior have been identified through genome-wide association studies. Circulating levels of the nicotine metabolite cotinine is a marker of recent smoking exposure. Hence, genetic variants influencing smoking behavior are expected to be associated with cotinine levels. Methods: We conducted an analysis in a lung cancer case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We investigated the effects of single-nucleotide polymorphisms (SNP) previously associated with smoking behavior on (i) circulating cotinine and (ii) lung cancer risk. A total of 894 cases and 1,805 controls were analyzed for cotinine and genotyped for 10 polymorphisms on 7p14, 8p11, 10q23, 15q25, and 19q13. Results: Two variants in the nicotinic acetylcholine receptor subunit genes CHRNA5 and CHRNA3 on 15q25, rs16969968 and rs578776, were associated with cotinine (P = 0.001 and 0.03, respectively) in current smokers and with lung cancer risk (P < 0.001 and P 0.001, respectively). Two 19q13 variants, rs7937 and rs4105144, were associated with increased cotinine (P = 0.003 and P < 0.001, respectively) but decreased lung cancer risk (P = 0.01 for both, after adjusting for cotinine). Variants in 7p14, 8p11, and 10q23 were not associated with cotinine or lung cancer risk. Conclusions: 15q25 and 19q13 SNPs were associated with circulating cotinine. The directions of association for 15q25 variants with cotinine were in accordance with that expected of lung cancer risk, whereas SNPs on 19q13 displayed contrasting associations of cotinine and lung cancer that require further investigation. Impact: This study is the largest to date investigating the effects of polymorphisms affecting smoking behavior on lung cancer risk using circulating cotinine measures as proxies for recent smoking behavior. Cancer Epidemiol Biomarkers Prev; 20(10); 2250-61. (C) 2011 AACR.
Author(s): Timofeeva MN, McKay JD, Smith GD, Johansson M, Byrnes GB, Chabrier A, Relton C, Ueland PM, Vollset SE, Midttun O, Nygard O, Slimani N, Romieu I, Clavel-Chapelon F, Boutron-Ruault MC, Fagherazzi G, Kaaks R, Teucher B, Boeing H, Weikert C, Bueno-de-Mesquita HB, van Gils C, Peeters PHM, Agudo A, Barricarte A, Huerta JM, Rodriguez L, Sanchez MJ, Larranaga N, Khaw KT, Wareham N, Allen NE, Travis RC, Gallo V, Norat T, Krogh V, Masala G, Panico S, Sacerdote C, Tumino R, Trichopoulou A, Lagiou P, Trichopoulos D, Rasmuson T, Hallmans G, Riboli E, Vineis P, Brennan P
Publication type: Article
Publication status: Published
Journal: Cancer Epidemiology, Biomarkers & Prevention
Year: 2011
Volume: 20
Issue: 10
Pages: 2250-2261
Print publication date: 23/08/2011
Acceptance date: 03/08/2011
ISSN (print): 1055-9965
ISSN (electronic): 1538-7755
Publisher: American Association for Cancer Research
URL: http://dx.doi.org/10.1158/1055-9965.EPI-11-0496
DOI: 10.1158/1055-9965.EPI-11-0496
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