Genetic variants in GTF2H1 and risk of lung cancer: a case-control analysis in a Chinese population.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wu, W; Liu, H; Lei, R; Chen, D; Zhang, S; Lv, J; Wang, Y; Fan, W; Qian, J; Jin, G; Ma, H; Miao, R; Hu, Z; Wang, H; Jin, L; Wei, Q; Shen, H; Huang, W; Lu, D

Published Date

  • February 2009

Published In

Volume / Issue

  • 63 / 2

Start / End Page

  • 180 - 186

PubMed ID

  • 18692935

Electronic International Standard Serial Number (EISSN)

  • 1872-8332

International Standard Serial Number (ISSN)

  • 0169-5002

Digital Object Identifier (DOI)

  • 10.1016/j.lungcan.2008.05.014

Language

  • eng