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The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia

  1. Author:
    Hsiung, C. A.
    Lan, Q.
    Hong, Y. C.
    Chen, C. J.
    Hosgood, H. D.
    Chang, I. S.
    Chatterjee, N.
    Brennan, P.
    Wu, C.
    Zheng, W.
    Chang, G. C.
    Wu, T. C.
    Park, J. Y.
    Hsiao, C. F.
    Kim, Y. H.
    Shen, H. B.
    Seow, A.
    Yeager, M.
    Tsai, Y. H.
    Kim, Y. T.
    Chow, W. H.
    Guo, H. A.
    Wang, W. C.
    Sung, S. W.
    Hu, Z. B.
    Chen, K. Y.
    Kim, J. H.
    Chen, Y.
    Huang, L. M.
    Lee, K. M.
    Lo, Y. L.
    Gao, Y. T.
    Liu, L.
    Huang, M. S.
    Jung, T. H.
    Jin, G. F.
    Caporaso, N.
    Yu, D. K.
    Kim, C. H.
    Su, W. C.
    Shu, X. O.
    Xu, P.
    Kim, I. S.
    Chen, Y. M.
    Ma, H. X.
    Shen, M.
    Cha, S. I.
    Tan, W.
    Chang, C. H.
    Sung, J. S.
    Zhang, M. F.
    Yang, T. Y.
    Park, K. H.
    Yuenger, J.
    Wang, C. L.
    Ryu, J. S.
    Xiang, Y. B.
    Deng, Q. F.
    Hutchinson, A.
    Kim, J. S.
    Cai, Q. Y.
    Landi, M. T.
    Yu, C. J.
    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, J. F.
    Chanock, S.
    Yang, P. C.
    Rothman, N.
    Lin, D. X.

  2. Author Address

    [Hsiung, Chao Agnes; Hsiao, Chin-Fu; Wang, Wen-Chang; Lo, Yen-Li; Chang, Chin-Hao; Hu, Chi-Yuan; Chang, Chung-Kai] Natl Hlth Res Inst, Inst Populat Hlth Sci, Div Biostat & Bioinformat, Zhunan, Taiwan. [Lan, Qing; Hosgood, H. Dean, III; Chatterjee, Nilanjan; Yeager, Meredith; Chow, Wong-Ho; Caporaso, Neil; Shen, Min; Hutchinson, Amy; Landi, Maria Teresa; Tucker, Margaret; Fraumeni, Joseph F., Jr.; Chanock, Stephen; Rothman, Nathaniel] NCI, Div Canc Epidemiol, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hong, Yun-Chul; Lee, Kyoung-Mu] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. [Hong, Yun-Chul; Kim, Jin Hee] Seoul Natl Univ, Inst Environm Med, Med Res Ctr, Seoul, South Korea. [Chen, Chien-Jen] Acad Sin, Genom Res Ctr, Taipei, Taiwan. [Chen, Chien-Jen; Yang, Shi-Yi] Natl Taiwan Univ, Grad Inst Epidemiol, Coll Publ Hlth, Taipei 10764, Taiwan. [Chang, I-Shou] Natl Hlth Res Inst, Natl Inst Canc Res, Zhunan, Taiwan. [Brennan, Paul; Boffetta, Paolo] Int Agcy Res Canc, F-69372 Lyon, France. [Wu, Chen; Huang, Liming; Yu, Dianke; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Etiol, Beijing 100037, Peoples R China. [Wu, Chen; Huang, Liming; Yu, Dianke; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Carcinogenesis, Beijing 100037, Peoples R China. [Wu, Chen; Huang, Liming; Yu, Dianke; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100037, Peoples R China. [Wu, Chen; Huang, Liming; Yu, Dianke; Tan, Wen; Lin, Dongxin] Peking Union Med Coll, Beijing 100021, Peoples R China. [Zheng, Wei; Shu, Xiao-Ou; Cai, Qiuyin] Vanderbilt Univ, Sch Med, Dept Med,Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Inst Med & Publ Hlth, Nashville, TN 37212 USA. [Chang, Gee-Chen; Yang, Tsung-Ying] Taichung Vet Gen Hosp, Div Chest Med, Dept Internal Med, Taichung, Taiwan. [Chang, Gee-Chen] Natl Chung Hsing Univ, Inst Biomed Sci, Taichung 40227, Taiwan. [Chang, Gee-Chen] China Med Univ, Sch Med, Taichung, Taiwan. [Wu, Tangchun; Guo, Huan; Liu, Li; Xu, Ping; Deng, Qifei] Huazhong Univ Sci & Technol, Sch Publ Hlth, Inst Occupat Med, Wuhan 430074, Peoples R China. [Wu, Tangchun; Guo, Huan; Liu, Li; Xu, Ping; Deng, Qifei] Huazhong Univ Sci & Technol, Sch Publ Hlth, Minist Educ, Key Lab Environm & Hlth, Wuhan 430074, Peoples R China. [Park, Jae Yong; Jung, Tae Hoon; Kim, Chang Ho] Kyungpook Natl Univ, Sch Med, Dept Internal Med, Taegu, South Korea. [Park, Jae Yong] Kyungpook Natl Univ, Sch Med, Dept Biochem, Taegu, South Korea. [Park, Jae Yong] Kyungpook Natl Univ Hosp, Canc Res Ctr, Taegu, South Korea. [Kim, Yeul Hong; Sung, Jae Sook; Park, Kyong Hwa; Kim, Jun Suk] Korea Univ, Anam Hosp, Genom Res Ctr Lung & Breast Ovarian Canc, Seoul, South Korea. [Kim, Yeul Hong; Sung, Jae Sook; Kim, Jun Suk] Korea Univ, Coll Med, Dept Internal Med, Seoul 136705, South Korea. [Kim, Yeul Hong; Sung, Jae Sook; Kim, Jun Suk] Korea Univ, Coll Med, Div Brain, Seoul 136705, South Korea. [Kim, Yeul Hong; Kim, Jun Suk] Korea Univ, Coll Med, Div Oncol Hematol, Dept Internal Med, Seoul 136705, South Korea. [Shen, Hongbing; Jin, Guangfu; Ma, Hongxia; Zhang, Mingfeng] Nanjing Med Univ, Dept Epidemiol & Biostat, Ctr Canc, Nanjing, Peoples R China. [Seow, Adeline; Chen, Ying] Natl Univ Singapore, Dept Epidemiol & Publ Hlth, Singapore 0511, Singapore. [Yeager, Meredith; Yuenger, Jeff] NCI, Core Genotyping Facil, Adv Technol Program,Dept Hlth & Human Serv, Sci Applicat Int Corporat Frederick,NIH, Frederick, MD 21701 USA. [Tsai, Ying-Huang; Wang, Chih-Liang] Chang Gung Mem Hosp, Dept Pulm & Crit Care, Taipei, Taiwan. [Tsai, Ying-Huang] Chang Gung Univ, Dept Resp Care, Taipei, Taiwan. [Kim, Young Tae; Park, Ju-Yeon] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea. [Kim, Young Tae; Kim, Joo Hyun] Seoul Natl Univ Hosp, Dept Thorac & Cardiovasc Surg, Clin Res Inst, Seoul 110744, South Korea. [Sung, Sook Whan] Seoul Natl Univ, Coll Med, Dept Thorac & Cardiovasc Surg, Seoul, South Korea. [Sung, Sook Whan] Seoul Natl Univ, Bundang Hosp, Dept Thorac & Cardiovasc Surg, Geongi Do, South Korea. [Chen, Kuan-Yu; Yu, Chong-Jen; Yang, Pan-Chyr] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Chen, Kuan-Yu; Yu, Chong-Jen; Yang, Pan-Chyr] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. [Gao, Yu-Tang; Xiang, Yongbing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Huang, Ming-Shyan; Hung, Jen-Yu] Kaohsiung Med Univ Hosp, Dept Internal Med, Kaohsiung, Taiwan. [Su, Wu-Chou; Lin, Chien-Chung] Natl Cheng Kung Univ Hosp, Dept Internal Med, Tainan 70428, Taiwan. [Su, Wu-Chou; Lin, Chien-Chung] Natl Cheng Kung Univ, Coll Med, Tainan 70101, Taiwan. [Chen, Yuh-Min; Perng, Reury-Perng] Taichung Vet Gen Hosp, Chest Dept, Taipei, Taiwan. [Chen, Yuh-Min] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan. [Ryu, Jeong-Seon] Inha Univ, Coll Med, Dept Internal Med, Inchon, South Korea. [Chen, Chih-Yi] China Med Univ Hosp, Ctr Canc, Taipei, Taiwan. [Chanock, Stephen] NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.;Hsiung, CA, Natl Hlth Res Inst, Inst Populat Hlth Sci, Div Biostat & Bioinformat, Zhunan, Taiwan.;hsiung@nhri.org.tw qingl@mail.nih.gov
    1. Year: 2010
    2. Date: Aug
  2. Journal: Plos Genetics
    1. 6
    2. 8
    3. Pages: 9
  4. Type of Article: Article
  5. Article Number: e1001051
  6. ISSN: 1553-7390
  1. 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 x 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 x 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 x 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.

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External Sources

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  2. DOI: 10.1371/journal.pgen.1001051
  3. View record in Web of Science®
  4. WOS: 000281383800007

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  1. Fiscal Year: FY2009-2010
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