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Genetic variants in ABCG1 are associated with survival of nonsmall-cell lung cancer patients.

Publication ,  Journal Article
Wang, Y; Liu, H; Ready, NE; Su, L; Wei, Y; Christiani, DC; Wei, Q
Published in: Int J Cancer
June 1, 2016

Cell membrane transporters and metabolic enzymes play a crucial role in the transportation of a wide variety of substrates that maintain homeostasis in biological processes. We explored associations between genetic variants in these genes and survival of nonsmall-cell lung cancer (NSCLC) patients by reanalyzing two datasets from published genome-wide association studies (GWASs). In the discovery by using the GWAS dataset of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, we evaluated associations of 1,245 single-nucleotide polymorphisms (SNPs) in genes of four transporter families and two metabolic enzyme families with survival of 1,185 NSCLC patients. We then performed a replication analysis in the Harvard University Lung Cancer study (LCS) with 984 NSCLC patients. Multivariate Cox proportional hazards regression and false discovery rate (FDR) corrections were performed to evaluate the associations. We identified that 21 genotyped SNPs in eight gene regions were significantly associated with survival with FDR ≤ 0.1 in the discovery dataset. Subsequently, we confirmed six SNPs, which were putative functional, in ABCG1 of the ATP-binding cassette transporter family in the replication dataset. In the pooled analysis, two tagging (at r(2)  > 0.8 for linkage disequilibrium with other replicated SNPs)/functional SNPs were independently associated with survival: rs225388 G > A [adjusted hazards ratio (HR) = 1.12, 95% confidence interval (CI) = 1.03-1.20, Ptrend  = 4.6 × 10(-3)] and rs225390 A > G (adjusted HR = 1.16, 95% CI = 1.07-1.25, Ptrend  = 3.8 × 10(-4) ). Our results indicated that genetic variants of ABCG1 may be predictors of survival of NSCLC patients.

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Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

June 1, 2016

Volume

138

Issue

11

Start / End Page

2592 / 2601

Location

United States

Related Subject Headings

  • Prognosis
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Neoplasm Staging
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate
  • Humans
  • Genotype
  • Genome-Wide Association Study
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, Y., Liu, H., Ready, N. E., Su, L., Wei, Y., Christiani, D. C., & Wei, Q. (2016). Genetic variants in ABCG1 are associated with survival of nonsmall-cell lung cancer patients. Int J Cancer, 138(11), 2592–2601. https://doi.org/10.1002/ijc.29991
Wang, Yanru, Hongliang Liu, Neal E. Ready, Li Su, Yongyue Wei, David C. Christiani, and Qingyi Wei. “Genetic variants in ABCG1 are associated with survival of nonsmall-cell lung cancer patients.Int J Cancer 138, no. 11 (June 1, 2016): 2592–2601. https://doi.org/10.1002/ijc.29991.
Wang Y, Liu H, Ready NE, Su L, Wei Y, Christiani DC, et al. Genetic variants in ABCG1 are associated with survival of nonsmall-cell lung cancer patients. Int J Cancer. 2016 Jun 1;138(11):2592–601.
Wang, Yanru, et al. “Genetic variants in ABCG1 are associated with survival of nonsmall-cell lung cancer patients.Int J Cancer, vol. 138, no. 11, June 2016, pp. 2592–601. Pubmed, doi:10.1002/ijc.29991.
Wang Y, Liu H, Ready NE, Su L, Wei Y, Christiani DC, Wei Q. Genetic variants in ABCG1 are associated with survival of nonsmall-cell lung cancer patients. Int J Cancer. 2016 Jun 1;138(11):2592–2601.
Journal cover image

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

June 1, 2016

Volume

138

Issue

11

Start / End Page

2592 / 2601

Location

United States

Related Subject Headings

  • Prognosis
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Neoplasm Staging
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate
  • Humans
  • Genotype
  • Genome-Wide Association Study