Genetic variants in ABCG1 are associated with survival of non-small cell lung cancer patients

ABSTRACT

Genetically determined 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 non-small cell lung cancer (NSCLC) patients by re-analyzing a selected dataset 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 r²>0.8 for LD with other replicated SNPs)/functional SNPs were independently associated with survival: rs225388 G>A (adjusted hazards ratio = 1.12, 95% confidence interval = 1.03-1.20, P_trend = 4.6 × 10⁻³) and rs225390 A>G (adjusted hazards ratio = 1.16, 95% confidence interval = 1.07-1.25, P_trend = 3.8 × 10⁻⁴). Our results indicated that genetic variants of ABCG1 may be predictors of survival of NSCLC patients. This article is protected by copyright. All rights reserved.

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