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

Takashi Kohno, Hideo Kunitoh, Yoko Shimada, Kouya Shiraishi, Yuko Ishii, Koichi Goto, Yuichiro Ohe, Yutaka Nishiwaki, Aya Kuchiba, Seiichiro Yamamoto, Hiroshi Hirose, Akira Oka, Noriko Yanagitani, Ryusei Saito, Hidetoshi Inoko, Jun Yokota

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)834-841
Number of pages8
JournalCarcinogenesis
Volume31
Issue number5
DOIs
Publication statusPublished - 2010 Jan 8

ASJC Scopus subject areas

  • Cancer Research

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