Genetic variant in TP63 on locus 3q28 is associated with risk of lung adenocarcinoma among never-smoking females in Asia

H. Dean Hosgood, Wen Chang Wang, Yun Chul Hong, Jiu Cun Wang, Kexin Chen, I. Shou Chang, Chien Jen Chen, Daru Lu, Zhihua Yin, Chen Wu, Wei Zheng, Biyun Qian, Jae Yong Park, Yeul Hong Kim, Nilanjan Chatterjee, Ying Chen, Gee Chen Chang, Chin Fu Hsiao, Meredith Yeager, Ying Huang TsaiHu Wei, Young Tae Kim, Wei Wu, Zhenhong Zhao, Wong Ho Chow, Xiaoling Zhu, Yen Li Lo, Sook Whan Sung, Kuan Yu Chen, Jeff Yuenger, Joo Hyun Kim, Liming Huang, Ying Hsiang Chen, Yu Tang Gao, Jin Hee Kim, Ming Shyan Huang, Tae Hoon Jung, Neil Caporaso, Xueying Zhao, Zhang Huan, Dianke Yu, Chang Ho Kim, Wu Chou Su, Xiao Ou Shu, In San Kim, Bryan Bassig, Yuh Min Chen, Sung Ick Cha, Wen Tan, Hongyan Chen, Tsung Ying Yang, Jae Sook Sung, Chih Liang Wang, Xuelian Li, Kyong Hwa Park, Chong Jen Yu, Jeong Seon Ryu, Yongbing Xiang, Amy Hutchinson, Jun Suk Kim, Qiuyin Cai, Maria Teresa Landi, Kyoung Mu Lee, Jen Yu Hung, Ju Yeon Park, Margaret Tucker, Chien Chung Lin, Yangwu Ren, Reury Perng Perng, Chih Yi Chen, Li Jin, Kun Chieh Chen, Yao Jen Li, Yu Fang Chiu, Fang Yu Tsai, Pan Chyr Yang, Joseph F. Fraumeni, Adeline Seow, Dongxin Lin, Baosen Zhou, Stephen Chanock, Chao Agnes Hsiung, Nathaniel Rothman, Qing Lan

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Abstract

A recent genome-wide association study (GWAS) of subjects from Japan and South Korea reported a novel association between the TP63 locus on chromosome 3q28 and risk of lung adenocarcinoma (p = 7.3 × 10 -12); however, this association did not achieve genome-wide significance (p ≠10 -7) among never-smoking males or females. To determine if this association with lung cancer risk is independent of tobacco use, we genotyped the TP63 SNPs reported by the previous GWAS (rs10937405 and rs4488809) in 3,467 never-smoking female lung cancer cases and 3,787 never-smoking female controls from 10 studies conducted in Taiwan, Mainland China, South Korea, and Singapore. Genetic variation in rs10937405 was associated with risk of lung adenocarcinoma [n = 2,529 cases; p = 7.1 × 10 -8; allelic risk = 0.80, 95% confidence interval (CI) = 0.74-0.87]. There was also evidence of association with squamous cell carcinoma of the lung (n = 302 cases; p = 0.037; allelic risk = 0.82, 95% CI = 0.67-0.99). Our findings provide strong evidence that genetic variation in TP63 is associated with the risk of lung adenocarcinoma among Asian females in the absence of tobacco smoking.

Original languageEnglish
Pages (from-to)1197-1203
Number of pages7
JournalHuman Genetics
Volume131
Issue number7
DOIs
StatePublished - 1 Jul 2012

Cite this

Hosgood, H. D., Wang, W. C., Hong, Y. C., Wang, J. C., Chen, K., Chang, I. S., Chen, C. J., Lu, D., Yin, Z., Wu, C., Zheng, W., Qian, B., Park, J. Y., Kim, Y. H., Chatterjee, N., Chen, Y., Chang, G. C., Hsiao, C. F., Yeager, M., ... Lan, Q. (2012). Genetic variant in TP63 on locus 3q28 is associated with risk of lung adenocarcinoma among never-smoking females in Asia. Human Genetics, 131(7), 1197-1203. https://doi.org/10.1007/s00439-012-1144-8