J Cancer 2019; 10(7):1772-1780. doi:10.7150/jca.26722 This issue
Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China
Although the impact and potential mechanisms of p53 polymorphisms on human malignancies have been intensively studied, analyses for association between p53 polymorphisms and colorectal cancer (CRC) risk were still limited to some common variants. Moreover, the majority of previous studies did not classify the specimens of CRC based on tumor location. This case-control study aimed to evaluate the association of five p53 polymorphisms (rs1042522, rs12947788, rs1625895, rs2909430 and rs12951053) with the risk of low rectal cancer (LRC) and investigate the prognostic significance. A total of 347 cases and 353 controls from a Chinese population were recruited and genotyped using KASP assay. Individuals carrying the variant rs12947788 A allele were observed to associate with an increased risk of LRC. After stratification for clinicopathological parameters, rs12947788 was significantly co-related with the histological type of LRC under a dominant model. Although none of the selected p53 polymorphisms was significantly associated with patient prognosis in total population, significant associations with the overall survival were revealed in the heterozygosis carriers vs. wild type carriers model through subgroup analyses based on clinical characteristics. Moreover, haplotype analyses showed that C-A-G-A-A haplotype was associated with a significantly higher LRC risk as compared to the other haplotypes. In low rectal cancer, P53 protein expression was obviously higher in p53 rs1042522 mutant carriers than in other genotypes. Our study further proves the involvement of p53 polymorphisms in pathogenesis of LRC and may provide potential therapeutic implications.
Keywords: p53, polymorphisms, low rectal cancer, risk, prognosis