Genetic variants of CHEK1, PRIM2 and CDK6 in the mitotic phase-related pathway are associated with nonsmall cell lung cancer survival

Abstract

The mitotic phase is a vital step in cell division and may be involved in cancer progression, but it remains unclear whether genetic variants in mitotic phase-related pathways genes impact the survival of these patients. Here, we investigated associations between 31 032 single nucleotide polymorphisms (SNPs) in 368 mitotic phase-related pathway genes and overall survival (OS) of patients with nonsmall cell lung cancer (NSCLC). We assessed the associations in a discovery data set of 1185 NSCLC patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and validated the findings in another data set of 984 patients from the Harvard Lung Cancer Susceptibility Study. As a result, we identified three independent SNPs (ie, CHEK1 rs76744140 T>C, PRIM2 rs6939623 G>T and CDK6 rs113181986 G>C) to be significantly associated with NSCLC OS with an adjusted hazard ratio of 1.29 (95% confidence interval = 1.11-1.49, P = 8.26 × 10−4), 1.26 (1.12-1.42, 1.10 × 10−4) and 0.73 (0.63-0.86, 1.63 × 10−4), respectively. Moreover, the number of combined unfavorable genotypes of these three SNPs was significantly associated with NSCLC OS and disease-specific survival in the PLCO data set (Ptrend