p53 Arg72Pro polymorphism and risk of colorectal adenoma and cancer

Abstract

A single nucleotide polymorphism (SNP) at codon 72 of the p53 gene (Arg72Pro) alters the p53 protein structure and affects its activity. We investigated this SNP in relation to colorectal adenoma and cancer among men and women from case-control studies nested within the Nurses' Health Study, the Health Professionals Follow-up Study and the Physicians' Health Study. Among 856 colorectal adenoma cases and 1,184 controls, we observed a modest association with p53 Arg72Pro genotype (multivariate odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.04-1.50 for Arg/Pro and Pro/Pro vs. Arg/Arg). This association did not vary by colorectal site or by sex. Among 442 colorectal cancer cases and 904 controls, we observed no significant overall association between p53 Arg72Pro genotype and colorectal cancer (multivariate OR = 1.14, 95% CI = 0.90-1.45). However, when colorectal site and sex was accounted for, the Pro carrier genotypes compared to Arg/Arg were associated with an increased risk of proximal colon cancers in women (multivariate OR = 2.59, 95% CI = 1.49-4.52) though not with distal colon or rectal cancers, while among men the same genotypes were associated with an increased risk of distal colon cancers (multivariate OR = 2.09, 95% CI = 1.28-3.40) but not proximal colon or rectal cancers. Our results suggest that Arg72Pro may play a role in the early stages of colorectal neoplasia and possibly in progression to invasive disease, depending on site and sex.