期刊
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
卷 102, 期 13, 页码 959-971出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/jnci/djq178
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资金
- US National Institutes of Health (NIH)
- National Cancer Institute (NCI) [R03 CA133939-01, R01 CA092039, CA55769, CA127219, CA121197, CA133996, CA77118, CA80127, CA84354, PO1 CA68384, K07 CA104231, K99CA131477, CA55874, CA85997]
- Deutsche Forschungsgemeinschaft (DFG) [BI 576/2-1, BI 576/2-2]
- Helmholtz Association, Germany
- Deutsche Krebshilfe
- European Commission (Sante et protection des consommateurs [SANCO])
- German Cancer Aid
- German Cancer Research Center
- German Federal Ministry of Education and Research
- National Institute of Environmental Health Sciences [ES06717]
- Ministry of Education, Science, Sports, Culture and Technology of Japan [17015052]
- Ministry of Health, Labor and Welfare of Japan [H20-002]
- National Medical Research Council, Singapore [NMRC/1075/2006]
- Norwegian Cancer Society
- NIH [DA11386, CA90833, CA09142, ES011667]
- Alper Research Center for Environmental Genomics of the UCLA's Jonsson Comprehensive Cancer Center
- National Center for Research Resources of the NIH [P20RR018787]
- United States-Israel Binational Science Foundation (BSF) [2003159]
- Pennsylvania Department of Health [PA-DOH 4100038714, PA-DOH 4100038715]
- Baden-Wurttemberg Ministry of Research, Science and Arts
- Helmholtz Association, Germany [VH.VI-143]
- Monika Kutzner Stiftung
- Canadian Cancer Society [20214]
Background Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies. Methods Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case-control studies for 11 645 lung cancer case patients and 14 954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided. Results Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, P-trend = 2 x 10(-26)), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, P-trend = 1 x 10(-10)) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, P-trend = 5 x 10(-8)) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, P-trend = 2 x 10(-5); rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, P-trend = .007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer. Conclusions In this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histology.
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