Association of GWAS-identified lung cancer susceptibility loci with survival length in patients with small-cell lung cancer treated with platinum-based chemotherapy.

Abstract

Genetic variants have been shown to affect length of survival in cancer patients. This study explored the association between lung cancer susceptibility loci tagged by single-nucleotide polymorphisms (SNPs) identified in the genome-wide association studies and length of survival in small-cell lung cancer (SCLC). Eighteen SNPs were genotyped among 874 SCLC patients and Cox proportional hazards regression was used to examine the effects of genotype on survival length under an additive model with age, sex, smoking status and clinical stage as covariates. We identified 3 loci, 20q13.2 (rs4809957G >A), 22q12.2 (rs36600C >T) and 5p15.33 (rs401681C >T), significantly associated with the survival time of SCLC patients. The adjusted hazard ratio (HR) for patients with the rs4809957 GA or AA genotype was 0.80 (95% CI, 0.66-0.96; P = 0.0187) and 0.73 (95% CI, 0.55-0.96; P = 0.0263) compared with the GG genotype. Using the dominant model, the adjusted HR for patients carrying at least one T allele at rs36600 or rs401681 was 0.78 (95% CI, 0.63-0.96; P = 0.0199) and 1.29 (95% CI, 1.08-1.55; P = 0.0047), respectively, compared with the CC genotype. Stratification analyses showed that the significant associations of these 3 loci were only seen in smokers and male patients. The rs4809957 SNP was only significantly associated with length of survival of patients with extensive-stage but not limited-stage tumor. These results suggest that some of the lung cancer susceptibility loci might also affect the prognosis of SCLC.

• Authors: Dong Li, Lixuan Wei, Binghe Xu, Dianke Yu, Jiang Chang, Peng Yuan, Zhongli Du, Wen Tan, Hongbing Shen, Tangchun Wu, Chen Wu, Dongxin Lin
• Journal: PloS one (PLoS One) Vol. 9 Issue 11 Pg. e113574 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25415319 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Etoposide
• Carboplatin

Topics

• Adult
• Aged
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Carboplatin (administration & dosage, therapeutic use)
• Chromosomes, Human, Pair 20 (genetics)
• Chromosomes, Human, Pair 22 (genetics)
• Chromosomes, Human, Pair 5 (genetics)
• Etoposide (administration & dosage, therapeutic use)
• Female
• Genetic Loci
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Humans
• Lung Neoplasms (drug therapy, genetics, mortality)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Small Cell Lung Carcinoma (drug therapy, genetics, mortality)
• Survival Analysis
• Treatment Outcome