Impact of TP53 polymorphisms (IVS3 + 40-41ins16, EX4 215G > C and IVS6 + 62G > A) on the risk of endometrial cancer, survival and hazard ratio of the patients

Abstract

TP53 is most frequently mutated gene in various cancers. Reports suggest that TP53 mutations are more prevalent in endometrial cancer (EC). Spectra of TP53 mutations vary within the sub-types of endometrial cancer. Studies on association of TP53 polymorphisms (IVS3+40-41ins16, EX4 215G>C and IVS6+62G>A) with EC are limited. Hence, we determined the association of TP53 polymorphisms with risk of EC, survival and hazard ratio (HR) of the patients. The study approved by the institute’s ethics committee (Ethical Committee reference no: IEC/2016/33 dated 04-02-2016) included 539 subjects, of which 359 were control subjects and 180 were confirmed cases of EC. Univariate and multivariate analyses were performed using SPSS 23.0. Haplotype analysis was done using Haploview 4.2. Variables with P < 0 .05 were considered statistically significant. IVS3+40-41ins16 polymorphism decreased the risk of EC, while EX4 215GC increased the risk by two folds. EX4 215G>C and IVS6+62G>A polymorphisms impacted the survival of patients with respect to clinical factors (grade, metastasis, recurrence and relapse). IVS6+62G>A did not impact the risk of cancer but impacted the HR of the patents, wherever grade was a covariate. Interestingly, BMI (≥23) decreased HR of the patients when either of the intronic polymorphisms was included in the Cox-model. There was weak and moderate LD (linkage disequilibrium) between the polymorphisms in control and cancer subjects, respectively. In conclusion, the study suggests that both the intronic and exonic polymorphisms of TP53 altered the risk of EC and affected the survival and HR of the patients.