期刊
NATURE GENETICS
卷 40, 期 5, 页码 616-622出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.109
关键词
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资金
- Cancer Research UK Funding Source: Medline
- NCI NIH HHS [P50 CA070907, R01CA55769, R01 CA127219-02, R01 CA133996, R01 CA121197-02, R01 CA121197, R01CA121197, R01 CA055769, R01 CA127219, P50 CA70907, R01CA133996] Funding Source: Medline
- NHGRI NIH HHS [N01HG65403] Funding Source: Medline
To identify risk variants for lung cancer, we conducted a multistage genome-wide association study. In the discovery phase, we analyzed 315,450 tagging SNPs in 1,154 current and former (ever) smoking cases of European ancestry and 1,137 frequency-matched, ever-smoking controls from Houston, Texas. For replication, we evaluated the ten SNPs most significantly associated with lung cancer in an additional 711 cases and 632 controls from Texas and 2,013 cases and 3,062 controls from the UK. Two SNPs, rs1051730 and rs8034191, mapping to a region of strong linkage disequilibrium within 15q25.1 containing PSMA4 and the nicotinic acetylcholine receptor subunit genes CHRNA3 and CHRNA5, were significantly associated with risk in both replication sets. Combined analysis yielded odds ratios of 1.32 (P < 1 x 10(-17)) for both SNPs. Haplotype analysis was consistent with there being a single risk variant in this region. We conclude that variation in a region of 15q25.1 containing nicotinic acetylcholine receptors genes contributes to lung cancer risk.
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