Individuals susceptible to lung adenocarcinoma defined by combined HLA-DQA1 and TERT genotypes.
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.
Kohno
Takashi
T
Biology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Kunitoh
Hideo
H
Shimada
Yoko
Y
Shiraishi
Kouya
K
Ishii
Yuko
Y
Goto
Koichi
K
Ohe
Yuichiro
Y
Nishiwaki
Yutaka
Y
Kuchiba
Aya
A
Yamamoto
Seiichiro
S
Hirose
Hiroshi
H
Oka
Akira
A
Yanagitani
Noriko
N
Saito
Ryusei
R
Inoko
Hidetoshi
H
Yokota
Jun
J
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*
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D011978:Receptors, Nicotinic; D019098:Telomerase; C069050:HLA-DQA1 antigen; C509186:TERT protein, human