Meta-analysis of genome-wide association studies identifies multiple lung cancer susceptibility loci in never-smoking Asian women

Wang, Zhaoming; Seow, Wei Jie; Shiraishi, Kouya; Hsiung, Chao A.; Matsuo, Keitaro; Liu, Jie; Chen, Kexin; Yamji, Taiki; Yang, Yang; Chang, I‐Shou; Wu, Chen; Hong, Yun Chul; Burdett, Laurie; Wyatt, Kathleen; Chung, Charles C.; Li, Shengchao A.; Yeager, Meredith; Hutchinson, Amy; Hu, Wei; Caporaso, Neil E.; Landi, Maria Teresa; Chatterjee, Nilanjan; Song, Minsun; Fraumeni, Joseph F.; Kohno, Takashi; Yokota, Jun; Kunitoh, Hideo; Ashikawa, Kyota; Momozawa, Yukihide; Daigo, Yataro; Mitsudomi, Tetsuya; Yatabe, Yasushi; Hida, Toyoaki; Hu, Zhibin; Dai, Juncheng; Ma, Hongxia; Jin, Guangfu; Song, Bao; Wang, Zhehai; Cheng, Sensen; Yin, Zhihua; Li, Xuelian; Ren, Yong; Guan, Peng; Chang, Jiang; Tan, Wen; Chen, Chien Jen; Chang, Gee Chen; Tsai, Ying Huang; Su, Wu Chou; Chen, Kuan‐Yu; Huang, Ming Shyan; Chen, Yuh Min; Zheng, Hong; Li, Haixin; Cui, Ping; Guo, Huan; Xu, Ping; Liu, Li; Iwasaki, Motoki; Shimazu, Taichi; Tsugane, Shoichiro; Zhu, Junjie; Jiang, Gening; Fei, Ke; Park, Jae Yong; Kim, Yeul Hong; Sung, Jae Sook; Park, Kyong Hwa; Kim, Young Tae; Jung, Yoo Jin; Kang, Chang Hyun; Park, In Kyu; Kim, Heung Dong; Jeon, Hyo Sung; Choi, Jin Eun; Choi, Yi Young; Kim, Jin Hee; Oh, In Jae; Kim, Young Chul; Sung, Sook Whan; Kim, Jun Suk; Yoon, Ho Il; Kweon, Sun-Seog; Shin, Min Ho; Seow, Adeline; Chen, Ying; Lim, Wei Yen; Li, Jianjun; Wong, Maria Pik; Lee, Victor; Bassig, Bryan A.; Tucker, Margaret A.; Berndt, Sonja I.; Chow, Wong Ho; Ji, Bu Tian; Wang, Junwen; Xu, Jianing; Sihoe, Alan D. L.; Ho, James Chung Man; Chan, John K.; Wang, Jiu Cun; Lu, Daru; Zhao, Xueying; Zhao, Zhenhong; Wu, Junjie; Chen, Hongyan; Jin, Li; Wei, Fusheng; Wu, Guoping; An, She Juan; Zhang, Xu-Chao; Su, Jian; Wu, Yi Long; Gao, Yu Tang; Xiang, Yong Bing; He, Xingzhou; Li, Jihua; Wang, Zheng; Shu, Xiao Ou; Cai, Qiuyin; Klein, Robert J.; Pao, William; Lawrence, Charles E.; Hosgood, H. Dean; Hsiao, Chin‐Fu; Chien, Li Hsin; Chen, Ying Hsiang; Chen, Chung Hsing; Wang, Wen Chang; Chen, Chih Yi; Wang, Chih Liang; Yu, Chong Jen; Chen, Huiling; Su, Yu; Tsai, Fang Yu; Chen, Yi Song; Li, Yao Jen; Yang, Tsung Ying; Lin, Chien Chung; Yang, Pan Chyr; Wu, Tangchun; Lin, Dong; Zhou, Baosen; Yu, Jinming; Shen, Hongbing; Kubo, Michiaki; Chanock, Stephen J.; Rothman, Nathaniel; Lan, Qing

doi:10.1093/hmg/ddv494

Cited by 49 publications

(32 citation statements)

References 43 publications

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“…FOXP proteins play key roles in cell cycle regulation and oncogenesis. Furthermore, meta-analysis, including those of studies in Japan and five other Asian countries, revealed that the FOXP4 SNP, rs7741164, is associated with a higher risk of lung cancer risk among never-smoking Asian females 22 , consistent with the aetiology of EGFR mutation-positive LADC 4 . Levels of FOXP4 mRNA expression in 403 non-cancerous lung tissues, as determined by real-time quantitative PCR, differed according to the rs2495239 SNP ( P by the linear regression test=0.023) genotype, suggesting high expression from the risk (A) allele ( Supplementary Table 15 ).…”

Section: Resultsmentioning

confidence: 92%

Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma

Shiraishi¹,

Okada

Takahashi

et al. 2016

Nat Commun

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Lung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East Asians (30–50%) than in European/Americans (10–20%). Here we investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA class II at 6p21.32 (rs2179920; P =5.1 × 10−17, per-allele OR=1.36) and 6p21.1 (FOXP4) (rs2495239; P=3.9 × 10−9, per-allele OR=1.19) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma. This study indicates that multiple genetic factors underlie the risk of lung adenocarcinomas with EGFR mutations.

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Section: Resultsmentioning

confidence: 92%

Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma

Shiraishi¹,

Okada

Takahashi

et al. 2016

Nat Commun

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“…2,3 Single nucleotide polymorphisms (SNPs) are the most common genetic variants that are found to be associated with cancer risk, including lung cancer. 4,5 Although genome-wide association studies (GWASs) have identified multiple SNPs to be associated with lung cancer risk, most of these SNPs have no annotated biological functions. 6,7 Therefore, we sought to perform a hypothesis-driven pathway-based analysis to identify possible functional SNPs that may be associated with lung cancer risk but have not been reported by previous single GWAS analysis.…”

Section: Introductionmentioning

confidence: 99%

Novel genetic variants in the P38MAPK pathway gene ZAK and susceptibility to lung cancer

Feng

Wang

Liu

et al. 2017

Molecular Carcinogenesis

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The P38MAPK pathway participates in regulating cell cycle, inflammation, development, cell death, cell differentiation, and tumorigenesis. Genetic variants of some genes in the P38MAPK pathway are reportedly associated with lung cancer risk. To substantiate this finding, we used six genome-wide association studies (GWASs) to comprehensively investigate associations of 14,904 single nucleotide polymorphisms (SNPs) in 108 genes of this pathway with lung cancer risk. We identified six significant lung cancer risk-associated SNPs in two genes (CSNK2B and ZAK) after correction for multiple comparisons by a false discovery rate (FDR) < 0.20. After removal of three CSNK2B SNPs that are located on the same locus previously reported GWAS, we performed LD analysis, SNP functional prediction and further analysis for two independent SNPs: rs3769201 and rs722864 in ZAK. We also expanded the analysis by including these two SNPs from additional GWAS datasets of Harvard University (984 cases and 970 controls) and deCODE (1,319 cases and 26,380 controls). The overall effects of these two SNPs were assessed using all eight GWAS datasets (OR=0.92, 95% CI=0.89–0.95, and P=1.03E-05 for rs3769201; OR=0.91, 95% CI=0.88–0.95, and P=2.03E-06 for rs722864). Finally, we performed an eQTL analysis and found that these two SNPs were significantly associated with ZAK mRNA expression levels in lymphoblastoid cell lines. In conclusion, the ZAK rs3769201 and rs722864 may be possible functional susceptibility loci for lung cancer risk.

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“…Lung cancer susceptibility loci have been identified in Asian never-smoking females, which are distinct from those identified in smokers of European ancestry, suggesting that the genetic susceptibility and etiology of lung cancer could differ between groups of distinct ancestral origin and more importantly by smoking status. [13][14][15] Comprehensive tobacco control programs are helping to decrease the incidence of lung cancer in smoking men. However, the oncogenic process seems to differ among nonsmoking females.…”

Section: Smoking and Lung Cancer In Asiamentioning

confidence: 99%

Progress in the Management of Early-Stage Non–Small Cell Lung Cancer in 2017

Donington

Kim

Tong

et al. 2018

Journal of Thoracic Oncology

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The landscape of care for early-stage non-small cell lung cancer continues to evolve. While some of the developments do not seem as dramatic as what has occurred in advanced disease in recent years, there is a continuous improvement in our ability to diagnose disease earlier and more accurately. We have an increased understanding of the diversity of early-stage disease and how to better tailor treatments to make them more tolerable without impacting efficacy. The International Association for the Study of Lung Cancer and the Journal of Thoracic Oncology publish this annual update to help readers keep pace with these important developments. Experts in the care of early-stage lung cancer patients have provided focused updates across multiple areas including screening, pathology, staging, surgical techniques and novel technologies, adjuvant therapy, radiotherapy, surveillance, disparities, and quality of life. The source for information includes large academic meetings, the published literature, or novel unpublished data from other international oncology assemblies.

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Meta-analysis of genome-wide association studies identifies multiple lung cancer susceptibility loci in never-smoking Asian women

Cited by 49 publications

References 43 publications

Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma

Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma

Novel genetic variants in the P38MAPK pathway gene ZAK and susceptibility to lung cancer

Progress in the Management of Early-Stage Non–Small Cell Lung Cancer in 2017

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