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

Research output: Contribution to journalArticle

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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 CLPTM1LTERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.

Original languageEnglish
JournalPLoS Genetics
Volume6
Issue number8
DOIs
Publication statusPublished - Aug 2010
Externally publishedYes

Fingerprint

adenocarcinoma
smoking
chromosome
genome
Chromosomes
Smoking
lungs
confidence interval
chromosomes
loci
Genome-Wide Association Study
Confidence Intervals
lung neoplasms
cancer
Lung Neoplasms
tobacco use
Genome
Far East
cigarettes
Homozygote

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Hsiung, C. A., Lan, Q., Hong, Y. C., Chen, C. J., Dean Hosgood, III., Chang, I. S., ... Lin, D. (2010). The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia. PLoS Genetics, 6(8). https://doi.org/10.1371/journal.pgen.1001051

The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia. / Hsiung, Chao Agnes; Lan, Qing; Hong, Yun Chul; Chen, Chien Jen; Dean Hosgood, III; Chang, I. Shou; Chatterjee, Nilanjan; Brennan, Paul; Wu, Chen; Zheng, Wei; Chang, Gee Chen; Wu, Tangchun; Park, Jae Yong; Hsiao, Chin Fu; Kim, Yeul Hong; Shen, Hongbing; Seow, Adeline; Yeager, Meredith; Tsai, Ying Huang; Kim, Young Tae; Chow, Wong Ho; Guo, Huan; Wang, Wen Chang; Sung, Sook Whan; Hu, Zhibin; Chen, Kuan Yu; Kim, Joo Hyun; Chen, Ying; Huang, Liming; Lee, Kyoung Mu; Lo, Yen Li; Gao, Yu Tang; Kim, Jin Hee; Liu, Li; Huang, Ming Shyan; Jung, Tae Hoon; Jin, Guangfu; Caporaso, Neil; Yu, Dianke; Kim, Chang Ho; Su, Wu Chou; Shu, Xiao Ou; Xu, Ping; Kim, In San; Chen, Yuh Min; Ma, Hongxia; Shen, Min; Cha, Sung Ick; Tan, Wen; Chang, Chin Hao; Sung, Jae Sook; Zhang, Mingfeng; Yang, Tsung Ying; Park, Kyong Hwa; Yuenger, Jeff; Wang, Chih Liang; Ryu, Jeong Seon; Xiang, Yongbing; Deng, Qifei; Hutchinson, Amy; Kim, Jun Suk; Cai, Qiuyin; Landi, Maria Teresa; Yu, Chong Jen; Park, Ju Yeon; Tucker, Margaret; Hung, Jen Yu; Lin, Chien Chung; Perng, Reury Perng; Boffetta, Paolo; Chen, Chih Yi; Chen, Kun Chieh; Yang, Shi Yi; Hu, Chi Yuan; Chang, Chung Kai; Fraumeni, Joseph F.; Chanock, Stephen; Yang, Pan Chyr; Rothman, Nathaniel; Lin, Dongxin.

In: PLoS Genetics, Vol. 6, No. 8, 08.2010.

Research output: Contribution to journalArticle

Hsiung, CA, Lan, Q, Hong, YC, Chen, CJ, Dean Hosgood, III, Chang, IS, Chatterjee, N, Brennan, P, Wu, C, Zheng, W, Chang, GC, Wu, T, Park, JY, Hsiao, CF, Kim, YH, Shen, H, Seow, A, Yeager, M, Tsai, YH, Kim, YT, Chow, WH, Guo, H, Wang, WC, Sung, SW, Hu, Z, Chen, KY, Kim, JH, Chen, Y, Huang, L, Lee, KM, Lo, YL, Gao, YT, Kim, JH, Liu, L, Huang, MS, Jung, TH, Jin, G, Caporaso, N, Yu, D, Kim, CH, Su, WC, Shu, XO, Xu, P, Kim, IS, Chen, YM, Ma, H, Shen, M, Cha, SI, Tan, W, Chang, CH, Sung, JS, Zhang, M, Yang, TY, Park, KH, Yuenger, J, Wang, CL, Ryu, JS, Xiang, Y, Deng, Q, Hutchinson, A, Kim, JS, Cai, Q, Landi, MT, Yu, CJ, Park, JY, Tucker, M, Hung, JY, Lin, CC, Perng, RP, Boffetta, P, Chen, CY, Chen, KC, Yang, SY, Hu, CY, Chang, CK, Fraumeni, JF, Chanock, S, Yang, PC, Rothman, N & Lin, D 2010, 'The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia', PLoS Genetics, vol. 6, no. 8. https://doi.org/10.1371/journal.pgen.1001051
Hsiung, Chao Agnes ; Lan, Qing ; Hong, Yun Chul ; Chen, Chien Jen ; Dean Hosgood, III ; Chang, I. Shou ; Chatterjee, Nilanjan ; Brennan, Paul ; Wu, Chen ; Zheng, Wei ; Chang, Gee Chen ; Wu, Tangchun ; Park, Jae Yong ; Hsiao, Chin Fu ; Kim, Yeul Hong ; Shen, Hongbing ; Seow, Adeline ; Yeager, Meredith ; Tsai, Ying Huang ; Kim, Young Tae ; Chow, Wong Ho ; Guo, Huan ; Wang, Wen Chang ; Sung, Sook Whan ; Hu, Zhibin ; Chen, Kuan Yu ; Kim, Joo Hyun ; Chen, Ying ; Huang, Liming ; Lee, Kyoung Mu ; Lo, Yen Li ; Gao, Yu Tang ; Kim, Jin Hee ; Liu, Li ; Huang, Ming Shyan ; Jung, Tae Hoon ; Jin, Guangfu ; Caporaso, Neil ; Yu, Dianke ; Kim, Chang Ho ; Su, Wu Chou ; Shu, Xiao Ou ; Xu, Ping ; Kim, In San ; Chen, Yuh Min ; Ma, Hongxia ; Shen, Min ; Cha, Sung Ick ; Tan, Wen ; Chang, Chin Hao ; Sung, Jae Sook ; Zhang, Mingfeng ; Yang, Tsung Ying ; Park, Kyong Hwa ; Yuenger, Jeff ; Wang, Chih Liang ; Ryu, Jeong Seon ; Xiang, Yongbing ; Deng, Qifei ; Hutchinson, Amy ; Kim, Jun Suk ; Cai, Qiuyin ; Landi, Maria Teresa ; Yu, Chong Jen ; Park, Ju Yeon ; Tucker, Margaret ; Hung, Jen Yu ; Lin, Chien Chung ; Perng, Reury Perng ; Boffetta, Paolo ; Chen, Chih Yi ; Chen, Kun Chieh ; Yang, Shi Yi ; Hu, Chi Yuan ; Chang, Chung Kai ; Fraumeni, Joseph F. ; Chanock, Stephen ; Yang, Pan Chyr ; Rothman, Nathaniel ; Lin, Dongxin. / The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia. In: PLoS Genetics. 2010 ; Vol. 6, No. 8.
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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 CLPTM1LTERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.",
author = "Hsiung, {Chao Agnes} and Qing Lan and Hong, {Yun Chul} and Chen, {Chien Jen} and {Dean Hosgood}, III and Chang, {I. Shou} and Nilanjan Chatterjee and Paul Brennan and Chen Wu and Wei Zheng and Chang, {Gee Chen} and Tangchun Wu and Park, {Jae Yong} and Hsiao, {Chin Fu} and Kim, {Yeul Hong} and Hongbing Shen and Adeline Seow and Meredith Yeager and Tsai, {Ying Huang} and Kim, {Young Tae} and Chow, {Wong Ho} and Huan Guo and Wang, {Wen Chang} and Sung, {Sook Whan} and Zhibin Hu and Chen, {Kuan Yu} and Kim, {Joo Hyun} and Ying Chen and Liming Huang and Lee, {Kyoung Mu} and Lo, {Yen Li} and Gao, {Yu Tang} and Kim, {Jin Hee} and Li Liu and Huang, {Ming Shyan} and Jung, {Tae Hoon} and Guangfu Jin and Neil Caporaso and Dianke Yu and Kim, {Chang Ho} and Su, {Wu Chou} and Shu, {Xiao Ou} and Ping Xu and Kim, {In San} and Chen, {Yuh Min} and Hongxia Ma and Min Shen and Cha, {Sung Ick} and Wen Tan and Chang, {Chin Hao} and Sung, {Jae Sook} and Mingfeng Zhang and Yang, {Tsung Ying} and Park, {Kyong Hwa} and Jeff Yuenger and Wang, {Chih Liang} and Ryu, {Jeong Seon} and Yongbing Xiang and Qifei Deng and Amy Hutchinson and Kim, {Jun Suk} and Qiuyin Cai and Landi, {Maria Teresa} and Yu, {Chong Jen} and Park, {Ju Yeon} and Margaret Tucker and Hung, {Jen Yu} and Lin, {Chien Chung} and Perng, {Reury Perng} and Paolo Boffetta and Chen, {Chih Yi} and Chen, {Kun Chieh} and Yang, {Shi Yi} and Hu, {Chi Yuan} and Chang, {Chung Kai} and Fraumeni, {Joseph F.} and Stephen Chanock and Yang, {Pan Chyr} and Nathaniel Rothman and Dongxin Lin",
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T1 - The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia

AU - Hsiung, Chao Agnes

AU - Lan, Qing

AU - Hong, Yun Chul

AU - Chen, Chien Jen

AU - Dean Hosgood, III

AU - Chang, I. Shou

AU - Chatterjee, Nilanjan

AU - Brennan, Paul

AU - Wu, Chen

AU - Zheng, Wei

AU - Chang, Gee Chen

AU - Wu, Tangchun

AU - Park, Jae Yong

AU - Hsiao, Chin Fu

AU - Kim, Yeul Hong

AU - Shen, Hongbing

AU - Seow, Adeline

AU - Yeager, Meredith

AU - Tsai, Ying Huang

AU - Kim, Young Tae

AU - Chow, Wong Ho

AU - Guo, Huan

AU - Wang, Wen Chang

AU - Sung, Sook Whan

AU - Hu, Zhibin

AU - Chen, Kuan Yu

AU - Kim, Joo Hyun

AU - Chen, Ying

AU - Huang, Liming

AU - Lee, Kyoung Mu

AU - Lo, Yen Li

AU - Gao, Yu Tang

AU - Kim, Jin Hee

AU - Liu, Li

AU - Huang, Ming Shyan

AU - Jung, Tae Hoon

AU - Jin, Guangfu

AU - Caporaso, Neil

AU - Yu, Dianke

AU - Kim, Chang Ho

AU - Su, Wu Chou

AU - Shu, Xiao Ou

AU - Xu, Ping

AU - Kim, In San

AU - Chen, Yuh Min

AU - Ma, Hongxia

AU - Shen, Min

AU - Cha, Sung Ick

AU - Tan, Wen

AU - Chang, Chin Hao

AU - Sung, Jae Sook

AU - Zhang, Mingfeng

AU - Yang, Tsung Ying

AU - Park, Kyong Hwa

AU - Yuenger, Jeff

AU - Wang, Chih Liang

AU - Ryu, Jeong Seon

AU - Xiang, Yongbing

AU - Deng, Qifei

AU - Hutchinson, Amy

AU - Kim, Jun Suk

AU - Cai, Qiuyin

AU - Landi, Maria Teresa

AU - Yu, Chong Jen

AU - Park, Ju Yeon

AU - Tucker, Margaret

AU - Hung, Jen Yu

AU - Lin, Chien Chung

AU - Perng, Reury Perng

AU - Boffetta, Paolo

AU - Chen, Chih Yi

AU - Chen, Kun Chieh

AU - Yang, Shi Yi

AU - Hu, Chi Yuan

AU - Chang, Chung Kai

AU - Fraumeni, Joseph F.

AU - Chanock, Stephen

AU - Yang, Pan Chyr

AU - Rothman, Nathaniel

AU - Lin, Dongxin

PY - 2010/8

Y1 - 2010/8

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AB - 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.

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