The intron 3 16bp duplication polymorphism of p53 (rs17878362) is not associated with increased risk of developing triple-negative breast cancer.

Abstract

Very little is known about the genetic risk factors associated with triple-negative breast cancer (TNBC), an aggressive clinical subtype characterised by the absence of ER, PR and HER2. p53, the tumour suppressor gene, is essential for maintaining genomic stability in response to cellular stress. In breast cancer, the mutation rates of TP53 vary depending on the subtype, such that ER-negative tumours have a high rate, and in ER-positive tumours they are less common. Previous studies have implicated the intronic polymorphism in TP53 (rs17878362; or PIN3) with an increased risk of developing breast cancer, although little has been discerned on its prevalence in different subtypes. In this study, we investigated the prevalence of the PIN3 genotype in the blood of cohorts with ER-positive and the ER-negative subtype TNBC, and assessed its association with outcome. We genotyped 656 TNBC and 648 ER-positive breast cancer patients, along with 436 controls, and compared the prevalence of polymorphism rs17878362 in these cohorts. We found there to be no differences in the prevalence of the PIN3 genotype between the ER-positive and TNBC cohorts. Furthermore, no statistically significant difference was observed in the outcome of patients in either cohort with respect to their PIN3 genotype. Taken together, our results do not support an association of the PIN3 genotype with increased breast cancer risk, either in ER-positive or ER-negative patients.