Genome-Wide Association Study Of Lung Adenocarcinoma And Relationship With Tumor EGFR Mutations Among Never-Smoking Women In Asia, And Comparison With Findings In Western Populations

Qing LAN, National Cancer Institute, United States
SEOW W. 1 , MATSUO K. 2 , HSIUNG C. 3 , SHIRAISHI K. 4 , HOSGOOD III D. 5 , LANDI M. 1 , ZHENG W. 6 , CAPORASO N. 1 , SHU X. 6 , DONGXIN L. 7 , CHEN K. 8 , SHEN H. 9 , KOHNO T. 4 , CHANOCK S. 1 , ROTHMAN N. 1

1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
2 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
3 Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
4 Division of Genome Biology, National Cancer Research Institute, Tokyo, Japan
5 Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA
6 Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA
7 Department of Etiology & Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
8 Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
9 Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China

Among never-smokers, rates of lung cancer in Asian women are among the highest in the world. We have previously shown that indoor use of coal for home heating and cooking is causally associated with risk of lung cancer among women in China. To provide further insight into the environmental and genetic etiology of lung cancer among never-smoking females in Asia, we formed the Female Lung Cancer Consortium in Asia (FLCCA) including study centers in Mainland China, Hong Kong, Taiwan, South Korea, Japan, and Singapore and conducted a multistage GWAS and meta-analysis of 10,780 cases of lung adenocarcinoma and 10,938 controls. We identified nine independent signals associated with risk of adenocarcinoma overall and a tenth signal (rs3817963, BTNL2) associated with risk of adenocarcinoma among cases with tumors that contained EGFR mutations. In addition, rs9387478 (ROS1-DCBLD1) and rs2179920 (HLA-DPB1) showed stronger effects in EGFR-positive compared to EGFR-negative cases. Comparison of the overall associations with findings in Western populations reported to date revealed that the majority of signals in our studies among Asians were distinct from those reported for Western populations. We also found evidence of gene-environment interactions between two GWAS findings and use of coal for indoor cooking and heating. Our results suggest that both environmental and distinct genetic variants may contribute to the excess of lung cancer among never-smoking women in this region.