A functional germline variant in the P53 polyadenylation signal and risk of esophageal squamous cell carcinoma

Aim: P53 plays a critical role in the maintenance of genomic stability as well as the control of cell growth and apoptosis. Recently, an uncommon P53 genetic variant (rs78378222) was reported to be significantly associated with multiple cancers in Caucasians in a genome-wide association study. rs78378222 locates in the 3'-untranslated region of the P53 gene, and this A-to-C polymorphism results in changes of the AATAAA polyadenylation signal to AATACA, which leads to impaired 3'-end processing of P53 mRNA and decreased P53 expression. Methods: We evaluated the association between this polymorphism and esophageal squamous cell carcinoma (ESCC) risk in a case-control cohort consisting of 405 ESCC patients and 810 healthy controls. Odds ratios (ORs) and 95% confidence intervals (as) were calculated by logistic regression. Results: We did observe this polymorphism with low minor allele frequency in Chinese Han population. Additionally, significantly increased ESCC risk was associated with P53 rs78378222 A>C polymorphism. Compared with rs78378222AA carriers, the OR of developing ESCC for AC carriers was 3.22 (95% CI = 1.71 - 6.33, P = 1.34 x 10(-4)). Conclusion: These results suggest that this functional uncommon P53 rs78378222 variant is associated with ESCC risk in the current Han Chinese population. (C) 2012 Elsevier B.V. All rights reserved.