Journal
NATURE COMMUNICATIONS
Volume 7, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/ncomms12451
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Funding
- Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development (AMED) [16ck0106096h0003]
- Japan Society for the Promotion of Science (JSPS) KAKENHI grant [15H05911, 15H05670, 15K14429, 22590516, 19390359]
- Princess Takamatsu Cancer Research Fund
- National Cancer Center Research and Development Fund [26-A-8, 26-A-1]
- Ministry of Education, Culture, Sports, Science, and Technology, Japan (MEXT)
- AMED
- MEXT
- Grants-in-Aid for Scientific Research [19390359, 15H05911, 15K10275, 15H05908, 22590516, 16H06277] Funding Source: KAKEN
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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 x 10(-17), per-allele OR = 1.36) and 6p21.1 (FOXP4) (rs2495239; P = 3.9 x 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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