Purpose: 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).
Methods: 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).
Results: 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).
Conclusions: Our finding suggested that survivin promoter polymorphisms -625G/C might influence the susceptibility to ESCC in the Chinese population, maybe by influencing survivin expression.