title: Genetic variants in ABCG1 are associated with survival of nonsmall-cell lung cancer patients.
abstract: 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.
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC.|Department of Medicine, Duke University School of Medicine, Durham, NC.
authors.forename: Yanru
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC.|Department of Medicine, Duke University School of Medicine, Durham, NC.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC.|Department of Medicine, Duke University School of Medicine, Durham, NC.
authors.forename: Neal E
authors.initials: NE
authors.lastname: Ready
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA.|Department of Epidemiology, Harvard School of Public Health, Boston, MA.
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA.|Department of Epidemiology, Harvard School of Public Health, Boston, MA.
authors.forename: Yongyue
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA.|Department of Epidemiology, Harvard School of Public Health, Boston, MA.|Department of Medicine, Massachusetts General Hospital, Boston, MA.
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC.|Department of Medicine, Duke University School of Medicine, Durham, NC.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
chemical_list: C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters
keywords: ABCG1; drug transporters; lung cancer; overall survival; single-nucleotide polymorphism