TY - JOUR
T1 - Individuals susceptible to lung adenocarcinoma defined by combined HLA-DQA1 and TERT genotypes
AU - Kohno, Takashi
AU - Kunitoh, Hideo
AU - Shimada, Yoko
AU - Shiraishi, Kouya
AU - Ishii, Yuko
AU - Goto, Koichi
AU - Ohe, Yuichiro
AU - Nishiwaki, Yutaka
AU - Kuchiba, Aya
AU - Yamamoto, Seiichiro
AU - Hirose, Hiroshi
AU - Oka, Akira
AU - Yanagitani, Noriko
AU - Saito, Ryusei
AU - Inoko, Hidetoshi
AU - Yokota, Jun
N1 - Funding Information:
Grants-in-Aid from the Ministry of Health, Labor and Welfare for the third-term Comprehensive 10 year Strategy for Cancer Control (J.Y.) and for Cancer Research, 19S-1 (T.K.); Ministry of Education, Culture, Sports, Science and Technology for Scientific Research on Priority Areas, KAKENHI 20014031 (T.K.).
PY - 2010/1/8
Y1 - 2010/1/8
N2 - 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.
AB - 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.
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U2 - 10.1093/carcin/bgq003
DO - 10.1093/carcin/bgq003
M3 - Article
C2 - 20061363
AN - SCOPUS:77952299453
SN - 0143-3334
VL - 31
SP - 834
EP - 841
JO - Carcinogenesis
JF - Carcinogenesis
IS - 5
ER -
