Increase In P53 Mutation Linked To Advanced Colorectal Cancer In African Americans

Understanding the relationship between molecular defects and differences in colorectal cancer incidence, aggressiveness and clinical outcomes is important in individualizing the treatment and in eliminating racial disparities.

"Several studies have identified a disparity between African-Americans and whites for colorectal cancer. What this study does is pinpoint a possible genetic cause," said Upender Manne, Ph.D., associate professor in the Department of Pathology at the University of Alabama at Birmingham.

For the current study, Manne and colleagues analyzed 137 colorectal adenocarcinomas from African-American patients and 236 colorectal adenocarcinomas from non-Hispanic whites. Researchers assessed these carcinomas for p53 mutations and genotyped for codon 72 polymorphisms.

Overall, whites and African-Americans had a similar rate of p53 mutations. However, the frequency of the Pro72 allele was higher in blacks at 17 percent compared with 7 percent among whites. By contrast, the Arg72 allele frequency was higher in whites at 36 percent than in African-Americans, where the frequency was 19 percent.

Presence of the Pro72 allele in blacks was associated with a more than two-fold increase in mortality due to colorectal cancer.

"This paper shows that in a subset of patients with the Pro72 allele, and the susceptibility to p53 mutations may be a possible molecular explanation for the racial disparity," said Manne.