Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Nat Genet. 2010 Oct;42(10):893-6. doi: 10.1038/ng.667. Epub 2010 Sep 26.
Lung cancer is the most common cause of death from cancer worldwide, and its incidence is increasing in East Asian and Western countries. To identify genetic factors that modify the risk of lung adenocarcinoma, we conducted a genome-wide association study in a Japanese cohort, with replication in two independent studies in Japanese and Korean individuals, in a total of 2,098 lung adenocarcinoma cases and 11,048 controls. The combined analyses identified two susceptibility loci for lung adenocarcinoma: TERT (rs2736100, combined P = 2.91 × 10⁻¹¹), odds ratio (OR) = 1.27) and TP63 (rs10937405, combined P = 7.26 × 10⁻¹²), OR = 1.31). Fine mapping of the region containing TP63 showed that a SNP (rs4488809) in intron 1 of TP63 showed the most significant association. Our results suggest that genetic variation in TP63 may influence susceptibility to lung adenocarcinoma in East Asian populations.
肺癌是全世界癌症死亡的最常见原因，其发病率在东亚和西方国家都在上升。为了确定能改变肺腺癌风险的遗传因素，我们在日本队列中进行了全基因组关联研究，在日本和韩国的两个独立研究中进行了复制，共包括 2098 例肺腺癌病例和 11048 例对照。综合分析确定了肺腺癌的两个易感位点：TERT(rs2736100，联合 P = 2.91×10⁻¹¹)，比值比（OR）=1.27)和 TP63(rs10937405，联合 P = 7.26×10⁻¹²)，OR=1.31)。TP63 包含区域的精细作图显示，TP63 内含子 1 中的 SNP(rs4488809) 与该区域关联最显著。我们的研究结果表明，TP63 中的遗传变异可能影响东亚人群肺腺癌的易感性。
