title: Genetic variants in GTF2H1 and risk of lung cancer: a case-control analysis in a Chinese population.
abstract: GTF2H1, the p62 subunit of the multiprotein complex transcription factor IIH (TFIIH), participates in both the nucleotide excision repair process and transcription control by specifically interacting with a variety of factors important in carcinogenesis. To elucidate the role of genetic variation in GTF2H1 in the etiology of lung cancer, we conducted a case-control study of 500 incident lung cancer cases and 517 controls in a Chinese population by genotyping six common single nucleotide polymorphisms (SNPs) in GTF2H1. An increased risk was associated with the variant genotypes of rs3802967 [adjusted odds ratio (OR)=1.38, 95% confidence interval (CI)=1.04-1.82], rs4150606 (adjusted OR=1.44, 95% CI=1.08-1.92), and rs4150678 (adjusted OR=1.37, 95% CI=1.04-1.81) in a dominant genetic model. The risk for rs3802967C/T+T/T genotypes was more pronounced among males subjects (P=0.002). In contrast, a decreased risk was associated with the rs4150667T/T genotype (adjusted OR=0.59, 95% CI=0.38-0.93) in a recessive model. Haplotype analysis showed that the haplotype "222212" (1 for common alleles and 2 for minor alleles) was associated with increased risk of lung cancer (P=0.03). Further evaluation using luciferase reporter constructs showed that the T allele of rs3802967 had higher luciferase expression, suggesting that the -79C-->T change may affect transcriptional activation of GTF2H1. Taken together, these results suggest that GTF2H1 polymorphisms/haplotypes may contribute to genetic susceptibility to lung cancer.
authors.affiliation: The State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Wu
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.forename: Rong
authors.initials: R
authors.lastname: Lei
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.forename: Shuyu
authors.initials: S
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Lv
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Fan
authors.forename: Ji
authors.initials: J
authors.lastname: Qian
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.forename: Ruifen
authors.initials: R
authors.lastname: Miao
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Daru
authors.initials: D
authors.lastname: Lu
mesh_terms: D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051758:Transcription Factor TFIIH; D019473:Transcription Factors, TFII / Q000235:genetics*
chemical_list: C072546:GTF2H1 protein, human; D010750:Phosphoproteins; D019473:Transcription Factors, TFII; D051758:Transcription Factor TFIIH