title: Individuals susceptible to lung adenocarcinoma defined by combined HLA-DQA1 and TERT genotypes.
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.
authors.affiliation: Biology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunitoh
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shimada
authors.forename: Kouya
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ishii
authors.forename: Koichi
authors.initials: K
authors.lastname: Goto
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nishiwaki
authors.forename: Aya
authors.initials: A
authors.lastname: Kuchiba
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirose
authors.forename: Akira
authors.initials: A
authors.lastname: Oka
authors.forename: Noriko
authors.initials: N
authors.lastname: Yanagitani
authors.forename: Ryusei
authors.initials: R
authors.lastname: Saito
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Inoko
authors.forename: Jun
authors.initials: J
authors.lastname: Yokota
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics*; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D006801:Humans; D015810:Linkage Disequilibrium; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics; D019098:Telomerase / Q000235:genetics*
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D011978:Receptors, Nicotinic; D019098:Telomerase; C069050:HLA-DQA1 antigen; C509186:TERT protein, human