1. The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia
- Author
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Hongxia Ma, Wen Chang Wang, Chang Ho Kim, Zhibin Hu, Kyong Hwa Park, Neil E. Caporaso, Jeff Yuenger, Ping Xu, Qiuyin Cai, Shi Yi Yang, Yen Li Lo, Kyoung Mu Lee, Mingfeng Zhang, Ju Yeon Park, Chih-Liang Wang, Wu Chou Su, Ying-Huang Tsai, Chao A. Hsiung, Iii Dean Hosgood, Nathaniel Rothman, Ming Shyan Huang, Li Liu, Nilanjan Chatterjee, Liming Huang, Chung Kai Chang, Sook Whan Sung, Tangchun Wu, Chin-Fu Hsiao, Joseph F. Fraumeni, Chong-Jen Yu, Joohyun Kim, Qifei Deng, Margaret A. Tucker, Yuh Min Chen, Chien Chung Lin, Paolo Boffetta, Tsung-Ying Yang, I. Shou Chang, Chi Yuan Hu, Yong-Bing Xiang, Kuan-Yu Chen, Paul Brennan, Maria Teresa Landi, Amy Hutchinson, Wei Zheng, Qing Lan, Min Shen, Chien-Jen Chen, Adeline Seow, Guangfu Jin, Kun-Chieh Chen, Ying Chen, Gee-Chen Chang, Huan Guo, Wong Ho Chow, Xiao-Ou Shu, Jun Suk Kim, Young Tae Kim, Pan-Chyr Yang, Tae Hoon Jung, In San Kim, Chin-Hao Chang, Yu Tang Gao, Meredith Yeager, Chen Wu, Jeong Seon Ryu, Sung Ick Cha, Jae Sook Sung, Jae Yong Park, Dongxin Lin, Yeul Hong Kim, Reury Perng Perng, Jen Yu Hung, Stephen J. Chanock, Wen Tan, Yun Chul Hong, Chih Yi Chen, Jin Hee Kim, Dianke Yu, Hongbing Shen, Hsiung, C.A., Lan, Q., Hong, Y.C., Chen, C.-J., Dean Hosgood, H., Chang, I.-S., Chatterjee, N., Brennan, P., Wu, C., Zheng, W., Chang, G.-C., Wu, T., Park, J.Y., Hsiao, C.-F., Kim, Y.H., Shen, H., Seow, A., Yeager, M., Tsai, Y.-H., Kim, Y.T., Chow, W.-H., Guo, H., Wang, W.-C., Sung, S.W., Hu, Z., Chen, K.-Y., Kim, J.H., Chen, Y., Huang, L., Lee, K.-M., Lo, Y.-L., Gao, Y.-T., Liu, L., Huang, M.-S., Jung, T.H., Jin, G., Caporaso, N., Yu, D., Kim, C.H., Su, W.-C., Shu, X.-O., Xu, P., Kim, I.-S., Chen, Y.-M., Ma, H., Shen, M., Cha, S.I., Tan, W., Chang, C.-H., Sung, J.S., Zhang, M., Yang, T.-Y., Park, K.H., Yuenger, J., Wang, C.-L., Ryu, J.-S., Xiang, Y., Deng, Q., Hutchinson, A., Kim, J.S., Cai, Q., Landi, M.T., Yu, C.-J., Park, J.-Y., Tucker, M., Hung, J.-Y., Lin, C.-C., Perng, R.-P., Boffetta, P., Chen, C.-Y., Chen, K.-C., Yang, S.-Y., Hu, C.-Y., Chang, C.-K., Fraumeni Jr., J.F., Chanock, S., Yang, P.-C., Rothman, N., and Lin, D.
- Subjects
Male ,Oncology ,Cancer Research ,Lung Neoplasms ,never-smoking ,0302 clinical medicine ,Risk Factors ,Genetics (clinical) ,Genetics ,0303 health sciences ,Middle Aged ,3. Good health ,female ,030220 oncology & carcinogenesis ,Chromosomes, Human, Pair 5 ,Adenocarcinoma ,Research Article ,Adult ,medicine.medical_specialty ,Asia ,lcsh:QH426-470 ,Single-nucleotide polymorphism ,Locus (genetics) ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Asian People ,Internal medicine ,medicine ,Adenocarcinoma of the lung ,Humans ,Genetic Predisposition to Disease ,Allele ,Lung cancer ,Genetics and Genomics/Cancer Genetics ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Aged ,030304 developmental biology ,Case-control study ,Genetics and Genomics ,lung adenocarcinoma ,medicine.disease ,Minor allele frequency ,lcsh:Genetics ,Case-Control Studies ,5p15.33 locu ,Genome-Wide Association Study - Abstract
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 CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma., Author Summary Worldwide, approximately 15% of lung cancer cases occur among nonsmokers. Genome-wide association studies (GWAS) of lung cancer conducted in populations of European background have identified three regions on chromosomes 5, 6, and 15 that harbor genetic variants that confer risk for lung cancer. Prior studies were conducted primarily in cigarette smokers, raising the possibility that the associations could be related to tobacco use, lung carcinogenesis, or both. A GWAS of lung cancer among never-smokers is an optimal setting to discover effects that are independent of smoking. Since most women in Asia do not smoke, we conducted a GWAS of lung adenocarcinoma among never-smoking females (584 cases, 585 controls) in Taiwan, and observed a region on chromosome 5 significantly associated with risk for lung cancer in never-smoking women. The finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls. To our knowledge, this study is the first reported GWAS of lung cancer in East Asian women, and together with the replication studies represents the largest genetic association study in this population. The findings provide insight into the genetic contribution of common variants to lung carcinogenesis.
- Published
- 2010
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