Polymorphisms of survivin promoter are associated with risk of esophageal squamous cell carcinoma

Abstract

Survivin is undetectable in normal adult tissues, but has been shown to be overexpressed in various cancers and has been regarded as a marker of malignancy. Polymorphisms which increase the expression of survivin are potential risk factors for esophageal carcinogenesis. The aim of this study is to genotype the survivin promoter polymorphisms namely -31G/C, -241T/C, -625G/C, and -644T/C in esophageal squamous cell cancer patients and controls and to identify a possible association between individual genetic variation and susceptibility to esophageal squamous cell carcinoma (ESCC). The expression of survivin in cancer tissues was detected by semiquantitative RT-PCR. A total of 221 Chinese ESCC patients and 268 cancer-free controls were evaluated for the four polymorphisms in survivin promoter. Polymorphisms were identified using the PCR-RFLP technique (-31G/C, -241T/C) or primer-introduced restriction analysis-PCR assay (-644T/C, -625G/C). Compared with the -625GG genotype, the -625CC genotype was associated with significant elevated risk of ESCC (OR = 2.404, 95% CI = 1.342-4.307). Furthermore, significant difference in survivin expression in esophageal squamous cell cancer tissues was found between subgroups with different -625G/C variants. When we examined the combined effect of the survivin promoter polymorphisms, the haplotypes constructed of -644T/C--625G/C--31G/C revealed significant associations with ESCC (global P = 0.0034). -644T--625C--31C was a risk haplotype for ESCC (P < 0.001) and -644T--625G--31C was a protective haplotype (P = 0.004). Our finding suggested that survivin promoter polymorphisms -625G/C might influence the susceptibility to ESCC in the Chinese population, maybe by influencing survivin expression.