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

• Published in: International journal of cancer 2016-06, Vol.138 (11), p.2592-2601
• Main Authors: Wang, Yanru, Liu, Hongliang, Ready, Neal E., Su, Li, Wei, Yongyue, Christiani, David C., Wei, Qingyi
• Format: Article
• Language: English
• Subjects: ABCG1; Aged; Aged, 80 and over; ATP Binding Cassette Transporter, Subfamily G, Member 1; ATP-Binding Cassette Transporters - genetics; Cancer; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - therapy; Confidence intervals; Datasets; drug transporters; Female; Genes; Genome-Wide Association Study; Genomes; Genotype; Humans; Kaplan-Meier Estimate; Lung cancer; Male; Medical research; Metabolism; Middle Aged; Neoplasm Staging; overall survival; Polymorphism; Polymorphism, Single Nucleotide; Prognosis; single‐nucleotide polymorphism
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.29991

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 r2 > 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. What's new? Certain genetic variants may predict lung cancer survival, according to new findings. Cell surface transporters can shuttle chemotherapy agents out of the cell, decreasing their effectiveness. In this paper, the authors investigated genetic variation in these proteins. Using published data from genome‐wide association studies, they identified 2 single nucleotide polymorphisms in the ABCG1 gene that associate with survival of NSCLC patients and could possibly be used in personalized prognoses and treatment plans.