Arg72Pro polymorphism of p53 may predict poor response to medical treatment in ulcerative colitis.

OBJECTIVE

Arg72Pro is a polymorphism commonly occurring in the proline-rich domain of Tp53. It can determine the development of different types of cancers, such as breast, lung, cervical, colorectal and hepatocellular carcinoma. Previous studies reported a correlation between Pro72 homozygosity and the clinical course of ulcerative colitis (UC). Our aim was to evaluate Arg72Pro genotype in patients who underwent proctocolectomy with ileo-pouch-anal anastomosis (IPAA) for UC compared with those who did not need surgery.

METHODS

The distribution of the different genotype of Arg72Pro was studied in 264 (234 medically treated [MT] and 30 IPAA) patients affected with UC observed between 2008 and 2011. IPAA patients underwent restorative proctocolectomy for refractory UC; MT ones were managed medically. Blood samples for genotyping were collected from all patients. Arg72Pro genotype analysis was carried out by polymerase chain reaction confronting two-pair primers (PCR-CTPP).

RESULTS

In MT patients (n=234) Arg/Arg, Arg/Pro and Pro/Pro frequencies were 51.28%, 41.02% and 7.7%, respectively, while in IPAA patients (n=30) were 53.4%, 23.3% and 23.3%, respectively. A statistically significant association was found between Pro/Pro and need for surgery (p=<0.0059, χ =7.59).

CONCLUSIONS

Our results showed that the Pro/Pro genotype was higher in IPAA (23.3%) than in MT (7.7%) patients. In UC patients the proline homozygosity identifies likeliness to resist to any standard pharmacologic therapy. It could potentially identify patients who would benefit from early surgical treatment, thereby reducing the rate of emergency colectomies and complications related to them.

BACKGROUND

Arg72Pro, Arg72Pro polymorphism, Ileopouch-anal anastomosis, IPAA, p53 polymorphism, Ulcerative colitis.