Genetic polymorphisms in 15q25 and 19q13 loci, cotinine levels, and risk of lung cancer in EPIC.
نویسندگان
چکیده
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.
منابع مشابه
Genetic polymorphisms in 15q25 and 19q13 loci, cotinine levels and risk of lung cancer in EPIC Running title: 15q25 and 19q13 loci, cotinine levels and lung cancer risk
Maria N. Timofeeva, James D. McKay, George Davey Smith, Mattias Johansson, Graham B. Byrnes, Amélie Chabrier, Caroline Relton, Per Magne Ueland, Stein Emil Vollset, Øivind Midttun, Ottar Nygård, Nadia Slimani, Isabelle Romieu, Françoise ClavelChapelon, Marie-Christine Boutron-Ruault , Guy Fagherazzi 8,9,10 Rudolf Kaaks, Birgit Teucher, Heiner Boeing, Cornelia Weikert, H Bas Bueno-de-Mesquita, C...
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ورودعنوان ژورنال:
- Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
دوره 20 10 شماره
صفحات -
تاریخ انتشار 2011