p53 codon 72 polymorphism in patients affected with ulcerative colitis.

BACKGROUND

The p53 tumor suppressor protein plays a fundamental role in maintaining genomic integrity through its ability to arrest the cell cycle in G1 and induce apoptosis. The proapoptotic activity of p53 seems to be strictly related to proline-rich regions, homologous to the SH3 binding domain. In the literature, reported data suggest a role for polymorphism at codon 72 of p53 in the predisposition to neoplastic transformation, although the results are still controversial. In this study, we investigated Arg72Pro polymorphism of p53 and related this polymorphism to clinical parameters in patients affected with ulcerative colitis (UC).

METHODS

We studied 243 consecutive outpatients affected with well-established UC. The control group comprised 142 healthy blood donors, with age and sex comparable to those of the patients.

RESULTS

p53 Pro/Pro was significantly related to the clinical course and duration of disease (odds ratio, 55.8 and 8.8, respectively). Nineteen of 24 patients with Pro homozygosity had a duration of disease >7 years. In contrast, 87 of 123 patients with Arg/Arg had short-standing UC (< or =7 yrs) and 66 of 96 with Arg/Pro had short-standing UC (chi-squared, 22.86; P < 0.0001). Thirty-four of 243 patients affected with UC had a positive family history for colorectal carcinoma (CRC). In those patients p53, Pro/Pro was significantly related to a family history of CRC (odds ratio, 38.1).

CONCLUSIONS

These preliminary data suggest that polymorphism at codon 72 of the p53 gene influences the clinical course of UC, with continuous disease associated with p53 Pro homozygosity.