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- Title
Individuals susceptible to lung adenocarcinoma defined by combined HLA-DQA1 and TERT genotypes.
- Authors
Kohno, Takashi; Kunitoh, Hideo; Shimada, Yoko; Shiraishi, Kouya; Ishii, Yuko; Goto, Koichi; Ohe, Yuichiro; Nishiwaki, Yutaka; Kuchiba, Aya; Yamamoto, Seiichiro; Hirose, Hiroshi; Oka, Akira; Yanagitani, Noriko; Saito, Ryusei; Inoko, Hidetoshi; Yokota, Jun
- Abstract
Adenocarcinoma (ADC) is the commonest histological type of lung cancer, and its weak association with smoking indicates the necessity to identify high-risk individuals for targeted screening and/or prevention. By a genome-wide association study (GWAS), we identified an association of polymorphisms in the 6p21.31 locus containing four human leukocyte antigen (HLA) class II genes with lung ADC risk. DQA1*03 of the HLA-DQA1 gene was defined as a risk allele with odds ratio (OR) of 1.36 [95% confidence interval (CI) = 1.21–1.54, P = 5.3 × 10−7] by analysis of 1656 ADC cases and 1173 controls. DQA1*03 and the minor allele for a polymorphism, rs2736100, in TERT, another lung cancer susceptibility locus identified in recent GWASs on Europeans and Americans, were indicated to independently contribute to ADC risk with per allele OR of 1.43 (95% CI = 1.31–1.56, P = 7.8 × 10−16). Individuals homozygous both for the DQA1*03 and minor TERT alleles were defined as high-risk individuals with an OR of 4.76 (95% CI = 2.53–9.47, P = 4.2 × 10−7). The present results indicated that individuals susceptible to lung ADC can be defined by combined genotypes of HLA-DQA1 and TERT.
- Subjects
ADENOCARCINOMA; LUNG cancer; DISEASE susceptibility; SMOKING; PHYSIOLOGICAL effects of tobacco
- Publication
Carcinogenesis, 2010, Vol 31, Issue 5, p834
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgq003