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Genetic variant in DNA repair gene GTF2H4 is associated with lung cancer risk: a large-scale analysis of six published GWAS datasets in the TRICL consortium.

Publication ,  Journal Article
Wang, M; Liu, H; Liu, Z; Yi, X; Bickeboller, H; Hung, RJ; Brennan, P; Landi, MT; Caporaso, N; Christiani, DC; Doherty, JA; Amos, CI; Wei, Q ...
Published in: Carcinogenesis
September 2016

DNA repair pathways maintain genomic integrity and stability, and dysfunction of DNA repair leads to cancer. We hypothesize that functional genetic variants in DNA repair genes are associated with risk of lung cancer. We performed a large-scale meta-analysis of 123,371 single nucleotide polymorphisms (SNPs) in 169 DNA repair genes obtained from six previously published genome-wide association studies (GWASs) of 12160 lung cancer cases and 16838 controls. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) using the logistic regression model and used the false discovery rate (FDR) method for correction of multiple testing. As a result, 14 SNPs had a significant odds ratio (OR) for lung cancer risk with P FDR < 0.05, of which rs3115672 in MSH5 (OR = 1.20, 95% CI = 1.14-1.27) and rs114596632 in GTF2H4 (OR = 1.19, 95% CI = 1.12-1.25) at 6q21.33 were the most statistically significant (P combined = 3.99×10(-11) and P combined = 5.40×10(-10), respectively). The MSH5 rs3115672, but not GTF2H4 rs114596632, was strongly correlated with MSH5 rs3131379 in that region (r (2) = 1.000 and r (2) = 0.539, respectively) as reported in a previous GWAS. Importantly, however, the GTF2H4 rs114596632 T, but not MSH5 rs3115672 T, allele was significantly associated with both decreased DNA repair capacity phenotype and decreased mRNA expression levels. These provided evidence that functional genetic variants of GTF2H4 confer susceptibility to lung cancer.

Duke Scholars

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

September 2016

Volume

37

Issue

9

Start / End Page

888 / 896

Location

England

Related Subject Headings

  • Transcription Factor TFIIH
  • Risk
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Lung Neoplasms
  • Humans
  • Genome-Wide Association Study
  • Genetic Variation
  • Genetic Predisposition to Disease
  • DNA Repair
 

Citation

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Wang, M., Liu, H., Liu, Z., Yi, X., Bickeboller, H., Hung, R. J., … Wei, Q. (2016). Genetic variant in DNA repair gene GTF2H4 is associated with lung cancer risk: a large-scale analysis of six published GWAS datasets in the TRICL consortium. Carcinogenesis, 37(9), 888–896. https://doi.org/10.1093/carcin/bgw070
Wang, Meilin, Hongliang Liu, Zhensheng Liu, Xiaohua Yi, Heike Bickeboller, Rayjean J. Hung, Paul Brennan, et al. “Genetic variant in DNA repair gene GTF2H4 is associated with lung cancer risk: a large-scale analysis of six published GWAS datasets in the TRICL consortium.Carcinogenesis 37, no. 9 (September 2016): 888–96. https://doi.org/10.1093/carcin/bgw070.
Wang, Meilin, et al. “Genetic variant in DNA repair gene GTF2H4 is associated with lung cancer risk: a large-scale analysis of six published GWAS datasets in the TRICL consortium.Carcinogenesis, vol. 37, no. 9, Sept. 2016, pp. 888–96. Pubmed, doi:10.1093/carcin/bgw070.
Wang M, Liu H, Liu Z, Yi X, Bickeboller H, Hung RJ, Brennan P, Landi MT, Caporaso N, Christiani DC, Doherty JA, TRICL Research Team, Amos CI, Wei Q. Genetic variant in DNA repair gene GTF2H4 is associated with lung cancer risk: a large-scale analysis of six published GWAS datasets in the TRICL consortium. Carcinogenesis. 2016 Sep;37(9):888–896.
Journal cover image

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

September 2016

Volume

37

Issue

9

Start / End Page

888 / 896

Location

England

Related Subject Headings

  • Transcription Factor TFIIH
  • Risk
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Lung Neoplasms
  • Humans
  • Genome-Wide Association Study
  • Genetic Variation
  • Genetic Predisposition to Disease
  • DNA Repair