The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia

Chao Agnes Hsiung, Qing Lan, Yun Chul Hong, Chien Jen Chen, III Dean Hosgood, I. Shou Chang, Nilanjan Chatterjee, Paul Brennan, Chen Wu, Wei Zheng, Gee Chen Chang, Tangchun Wu, Jae Yong Park, Chin Fu Hsiao, Yeul Hong Kim, Hongbing Shen, Adeline Seow, Meredith Yeager, Ying Huang Tsai, Young Tae KimWong Ho Chow, Huan Guo, Wen Chang Wang, Sook Whan Sung, Zhibin Hu, Kuan Yu Chen, Joo Hyun Kim, Ying Chen, Liming Huang, Kyoung Mu Lee, Yen Li Lo, Yu Tang Gao, Jin Hee Kim, Li Liu, Ming Shyan Huang, Tae Hoon Jung, Guangfu Jin, Neil Caporaso, Dianke Yu, Chang Ho Kim, Wu Chou Su, Xiao Ou Shu, Ping Xu, In San Kim, Yuh Min Chen, Hongxia Ma, Min Shen, Sung Ick Cha, Wen Tan, Chin Hao Chang, Jae Sook Sung, Mingfeng Zhang, Tsung Ying Yang, Kyong Hwa Park, Jeff Yuenger, Chih Liang Wang, Jeong Seon Ryu, Yongbing Xiang, Qifei Deng, Amy Hutchinson, Jun Suk Kim, Qiuyin Cai, Maria Teresa Landi, Chong Jen Yu, Ju Yeon Park, Margaret Tucker, Jen Yu Hung, Chien Chung Lin, Reury Perng Perng, Paolo Boffetta, Chih Yi Chen, Kun Chieh Chen, Shi Yi Yang, Chi Yuan Hu, Chung Kai Chang, Joseph F. Fraumeni, Stephen Chanock, Pan Chyr Yang, Nathaniel Rothman, Dongxin Lin

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Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10-7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30×10-11). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38×10-11). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60×10-20, allelic risk = 1.54, 95% Confidence Interval (CI) 1.41-1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40-1.87), and 2.35 (95% CI: 1.95-2.83), respectively. In summary, our results show that genetic variation in the CLPTM1LTERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.

Original languageEnglish
JournalPLoS Genetics
Issue number8
StatePublished - Aug 2010
Externally publishedYes


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