Dataset Information

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

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.

SUBMITTER: Hsiung CA

PROVIDER: S-EPMC2916850 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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

Hsiung Chao Agnes CA Lan Qing Q Hong Yun-Chul YC Chen Chien-Jen CJ Hosgood H Dean HD Chang I-Shou IS Chatterjee Nilanjan N Brennan Paul P Wu Chen C Zheng Wei W Chang Gee-Chen GC Wu Tangchun T Park Jae Yong JY Hsiao Chin-Fu CF Kim Yeul Hong YH Shen Hongbing H Seow Adeline A Yeager Meredith M Tsai Ying-Huang YH Kim Young Tae YT Chow Wong-Ho WH Guo Huan H Wang Wen-Chang WC Sung Sook Whan SW Hu Zhibin Z Chen Kuan-Yu KY Kim Joo Hyun JH Chen Ying Y Huang Liming L Lee Kyoung-Mu KM Lo Yen-Li YL Gao Yu-Tang YT Kim Jin Hee JH Liu Li L Huang Ming-Shyan MS Jung Tae Hoon TH Jin Guangfu G Caporaso Neil N Yu Dianke D Kim Chang Ho CH Su Wu-Chou WC Shu Xiao-Ou XO Xu Ping P Kim In-San IS Chen Yuh-Min YM Ma Hongxia H Shen Min M Cha Sung Ick SI Tan Wen W Chang Chin-Hao CH Sung Jae Sook JS Zhang Mingfeng M Yang Tsung-Ying TY Park Kyong Hwa KH Yuenger Jeff J Wang Chih-Liang CL Ryu Jeong-Seon JS Xiang Yongbing Y Deng Qifei Q Hutchinson Amy A Kim Jun Suk JS Cai Qiuyin Q Landi Maria Teresa MT Yu Chong-Jen CJ Park Ju-Yeon JY Tucker Margaret M Hung Jen-Yu JY Lin Chien-Chung CC Perng Reury-Perng RP Boffetta Paolo P Chen Chih-Yi CY Chen Kun-Chieh KC Yang Shi-Yi SY Hu Chi-Yuan CY Chang Chung-Kai CK Fraumeni Joseph F JF Chanock Stephen S Yang Pan-Chyr PC Rothman Nathaniel N Lin Dongxin D

PLoS genetics 20100805 8

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 assoc ...[more]

PMID: 20700438

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Project description:ImportanceEstimating absolute risk of lung cancer for never-smoking individuals is important to inform lung cancer screening programs.ObjectivesTo integrate data on environmental tobacco smoke (ETS), a known lung cancer risk factor, with a polygenic risk score (PRS) that captures overall genetic susceptibility, to estimate the absolute risk of lung adenocarcinoma (LUAD) among never-smokers in Taiwan.Design, setting, and participantsThe analyses were conducted in never-smoking women in the Taiwan Genetic Epidemiology Study of Lung Adenocarcinoma, a case-control study. Participants were recruited between September 17, 2002, and March 30, 2011. Data analysis was performed from January 17 to July 15, 2022.ExposuresA PRS was derived using 25 genetic variants that achieved genome-wide significance (P < 5 × 10-8) in a recent genome-wide association study, and ETS was defined as never exposed, exposed at home or at work, and exposed at home and at work.Main outcomes and measuresThe Individualized Coherent Absolute Risk Estimator software was used to estimate the lifetime absolute risk of LUAD in never-smoking women aged 40 years over a projected 40-year span among the controls by using the relative risk estimates for the PRS and ETS exposures, as well as age-specific lung cancer incidence rates for never-smokers in Taiwan. Likelihood ratio tests were conducted to assess an additive interaction between the PRS and ETS exposure.ResultsData were obtained on 1024 women with LUAD (mean [SD] age, 59.6 [11.4] years, 47.9% ever exposed to ETS at home, and 19.5% ever exposed to ETS at work) and 1024 controls (mean [SD] age, 58.9 [11.0] years, 37.0% ever exposed to ETS at home, and 14.3% ever exposed to ETS at work). The overall average lifetime 40-year absolute risk of LUAD estimated using PRS alone was 2.5% (range, 0.6%-10.3%) among women never exposed to ETS. When integrating both ETS and PRS data, the estimated absolute risk was 3.7% (range, 0.6%-14.5%) for women exposed to ETS at home or work and 5.3% (range, 1.2%-12.1%) for women exposed to ETS at home and work. A super-additive interaction between ETS and the PRS (P = 6.5 × 10-4 for interaction) was identified.Conclusions and relevanceThis study found differences in absolute risk of LUAD attributed to genetic susceptibility according to levels of ETS exposure in never-smoking women. Future studies are warranted to integrate these findings in expanded risk models for LUAD.

Dataset Information

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

Publications

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

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