Functional Promoter −1271G>C Variant of HSPB1 Predicts Lung Cancer Risk and Survival

Abstract

Purpose Heat-shock protein 27 (Hsp27), encoded by HSPB1, plays crucial roles in tumorigenesis and cell survival and is reported to be an independent prognosis marker for cancer. We hypothesized that genetic variants of the HSPB1 gene may be associated with lung cancer susceptibility and survival. Patients and Methods We first resequenced the full-length HSPB1 gene and then genotyped three selected tag single nucleotide polymorphisms (SNPs) in 1,152 paired Chinese lung cancer patient cases and controls. Another 500 paired patient cases and controls were used for replication. We also evaluated the roles of these tagSNPs in the overall survival of 248 patients with advanced non–small-cell lung cancer (NSCLC), and validated the results in another 335 patients with advanced NSCLC. The genotype-phenotype correlation was assessed in 309 workers with occupational exposure to polycyclic-aromatic hydrocarbons (PAHs) as well as by luciferase reporter assay and Western blotting analysis. Results The −1271C allele was...