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.
Highlights
Lung cancer is the leading cause of cancer deaths all over the world, and categorized into non-small cell lung cancer and small-cell lung cancer (SCLC) [1]
Up to the last follow-up date, 521 (59.6%) patients had died of SCLC, with a median survival time (MST) of 25 months; 353 (40.4%) patients are still alive
Based on the genome-wide association study (GWAS)-identified lung cancer susceptibility loci, this study explored whether they are associated with length of survival in SCLC patients
Summary
Lung cancer is the leading cause of cancer deaths all over the world, and categorized into non-small cell lung cancer and small-cell lung cancer (SCLC) [1]. Evidence has been accumulated to show that genetic variants might play a role in the prognosis and length of survival in patients [4, 5] The identification of such loci might have valuable implication in precision treatment of cancer. G SNP, located in the promoter region of the YAP1 gene which creates a transcription factor binding site and results in down-regulation of YAP1 expression, is significantly associated [4] This previous GWAS included only 245 samples in the discovery stage and 305 samples in the replication stage and the limited discovery power might obstruct to find most loci with small or moderate effect.
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