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    Carcinogenesis. 2010 May;31(5):834-41. Epub 2010 Jan 8.

    Individuals susceptible to lung adenocarcinoma defined by combined HLA-DQA1 and TERT genotypes.

    Kohno T, Kunitoh H, Shimada Y, Shiraishi K, Ishii Y, Goto K, Ohe Y, Nishiwaki Y, Kuchiba A, Yamamoto S, Hirose H, Oka A, Yanagitani N, Saito R, Inoko H, Yokota J.

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    Biology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.

    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 x 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 x 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 x 10(-7)). The present results indicated that individuals susceptible to lung ADC can be defined by combined genotypes of HLA-DQA1 and TERT.

    PMID:
    20061363
    [PubMed - indexed for MEDLINE]
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