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Pathway-analysis of published genome-wide association studies of lung cancer: A potential role for the CYP4F3 locus.

Publication ,  Journal Article
Yin, J; Liu, H; Liu, Z; Owzar, K; Han, Y; Su, L; Wei, Y; Hung, RJ; Brhane, Y; McLaughlin, J; Brennan, P; Bickeboeller, H; Rosenberger, A ...
Published in: Mol Carcinog
June 2017

The fatty acids (FAs) metabolism is suggested to play a pivotal role in the development of lung cancer, and we explored that by conducting a pathway-based analysis. We performed a meta-analysis of published datasets of six genome wide association studies (GWASs) from the Transdisciplinary Research in Cancer of the Lung (TRICL) consortium, which included 12 160 cases with lung cancer and 16 838 cancer-free controls. A total of 30 722 single-nucleotide polymorphisms (SNPs) from 317 genes relevant to FA metabolic pathways were identified. An additional dataset from the Harvard Lung Cancer Study with 984 cases and 970 healthy controls was also added to the final meta-analysis. In the initial meta-analysis, 26 of 28 SNPs that passed false discovery rate multiple tests were mapped to the CYP4F3 gene. Among the 26 top ranked hits was a proxy SNP, CYP4F3 rs4646904 (P = 8.65 × 10-6 , FDR = 0.018), which is suggested to change splicing pattern/efficiency and to be associated with gene expression levels. However, after adding data of rs4646904 from the Harvard GWAS, the significance in the combined analysis was reduced to P = 3.52 × 10-3 [odds ratio (OR) = 1.07, 95% confidence interval (95%CI) = 1.03-1.12]. Interestingly, the small Harvard dataset also pointed to the same direction of the association in subgroups of smokers (OR = 1.07) and contributed to a combined OR of 1.13 (95% CI = 1.06-1.20, P = 6.70 × 10-5 ). The results suggest that a potentially functional SNP in CYP4F3 (rs4646904) may contribute to the etiology of lung cancer, especially in smokers. Additional mechanistic studies are warranted to unravel the potential biological significance of the finding.

Duke Scholars

Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

June 2017

Volume

56

Issue

6

Start / End Page

1663 / 1672

Location

United States

Related Subject Headings

  • Signal Transduction
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Lung Neoplasms
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Loci
  • Fatty Acids
 

Citation

APA
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MLA
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Yin, J., Liu, H., Liu, Z., Owzar, K., Han, Y., Su, L., … Wei, Q. (2017). Pathway-analysis of published genome-wide association studies of lung cancer: A potential role for the CYP4F3 locus. Mol Carcinog, 56(6), 1663–1672. https://doi.org/10.1002/mc.22622
Yin, Jieyun, Hongliang Liu, Zhensheng Liu, Kouros Owzar, Younghun Han, Li Su, Yongyue Wei, et al. “Pathway-analysis of published genome-wide association studies of lung cancer: A potential role for the CYP4F3 locus.Mol Carcinog 56, no. 6 (June 2017): 1663–72. https://doi.org/10.1002/mc.22622.
Yin J, Liu H, Liu Z, Owzar K, Han Y, Su L, et al. Pathway-analysis of published genome-wide association studies of lung cancer: A potential role for the CYP4F3 locus. Mol Carcinog. 2017 Jun;56(6):1663–72.
Yin, Jieyun, et al. “Pathway-analysis of published genome-wide association studies of lung cancer: A potential role for the CYP4F3 locus.Mol Carcinog, vol. 56, no. 6, June 2017, pp. 1663–72. Pubmed, doi:10.1002/mc.22622.
Yin J, Liu H, Liu Z, Owzar K, Han Y, Su L, Wei Y, Hung RJ, Brhane Y, McLaughlin J, Brennan P, Bickeboeller H, Rosenberger A, Houlston RS, Caporaso N, Landi MT, Heinrich J, Risch A, Christiani DC, Amos CI, Wei Q. Pathway-analysis of published genome-wide association studies of lung cancer: A potential role for the CYP4F3 locus. Mol Carcinog. 2017 Jun;56(6):1663–1672.
Journal cover image

Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

June 2017

Volume

56

Issue

6

Start / End Page

1663 / 1672

Location

United States

Related Subject Headings

  • Signal Transduction
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Lung Neoplasms
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Loci
  • Fatty Acids