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Nat Commun. 2016 Aug 9;7:12451. doi: 10.1038/ncomms12451.

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

Author information

1
Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
2
Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
3
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Yokohama 230-0045, Japan.
4
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
5
Omics Research Center, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan.
6
Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama 113-8510, Japan.
7
Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo 150-0012, Japan.
8
Division of Translational Research, Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center Research Institute, Chiba 277-0882, Japan.
9
Center for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo 108-0071, Japan.
10
Department of Medical Oncology and Cancer Center, Shiga University of Medical Science, Otsu 520-2121, Japan.
11
Department of Integrative Center of General Surgery, Gunma University Hospital, Gunma 371-8511, Japan.
12
Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita 010-8543, Japan.
13
Department of Pathology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
14
Department of Pathology and Laboratory Medicine, Kansai Medical University, Osaka 573-1010, Japan.
15
Division of Thoracic Surgery, National Cancer Centre Hospital, Tokyo 104-0045, Japan.
16
Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
17
Department of Clinical Laboratories, National Cancer Center Hospital, Tokyo 104-0045, Japan.
18
Division of Clinical Laboratory, Kanagawa Cancer Center, Kanagawa 241-0815, Japan.
19
Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba 277-0882, Japan.
20
Department of Thoracic Surgery, National Cancer Center Hospital East, Chiba 277-0882, Japan.
21
Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Kanagawa 241-0815, Japan.
22
Department of Thoracic Surgery, Kanagawa Cancer Center, Kanagawa 241-0815, Japan.
23
Department of Pathology, Kanagawa Cancer Center, Kanagawa 241-0815, Japan.
24
Department of Thoracic Surgery, Graduate School of Medicine, Akita University, Akita 010-8543, Japan.
25
Division of Genetics, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
26
StaGen Co., Ltd., Tokyo 111-0051, Japan.
27
Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
28
Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
29
Bioresource Research Center, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
30
Department of Medicine and Department of Surgery, Center for Personalized Therapeutics, The University of Chicago, Chicago 60637, USA.
31
Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), 08916 Badalona, Spain.
32
Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
33
Division of Division of Molecular Medicine, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya 464-8681, Japan.

Abstract

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.

PMID:
27501781
PMCID:
PMC4980483
DOI:
10.1038/ncomms12451
[Indexed for MEDLINE]
Free PMC Article

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