R72P Polymorphism of TP53 in Ulcerative Colitis Patients is Associated with the Incidence of Colectomy, Use of Steroids and the Presence of a Positive Family History
Source: Pathology & Oncology Research, Volume 16, Number 4, December 2010 , pp. 563-568(6)
Abstract:P53 tumor suppressor protein is one of the pivotal regulators for genome integrity, cell cycle and apoptosis. The most commonly and extensively studied single nucleotide polymorphism (SNP) of p53 is Arg>Pro substitution on codon 72 (R72P). Although we know that the SNP has unique functional effects on the protein, its clinical significance is not clearly identified yet. Aim of the study was to access the relationship between R72P genotype distribution and clinical variables in patients with ulcerative colitis (UC) and colorectal cancer (CRC). Genomic DNA samples were extracted from 95 UC, 50 CRC, and 219 healthy controls. R72P genotype analysis was carried out with polymerase chain reaction following by restriction enzyme digestion. We observed that Pro allele carriage is a strong risk factor for CRC (OR = 3.03; 95%CI = 1.91–2.40; p = 0.003), but only modest association with UC (OR = 1.61; 95%CI = 0.98–2.65; p = 0.059) (Pro/Pro and Pro/Arg genotypes vs. Arg/Arg genotype). We did not find any correlation between genotype distribution of the polymorphism and clinical parameters of CRC, but in UC, Pro/Pro genotype was significantly related to an inflammatory bowel disease family history (OR = 8.0; 95%CI = 1.68–38.08, p = 0.015), and Arg/Pro genotype was significantly associated with the history of disease-related colectomy (OR = 17.77; 95%CI = 0.98–323.34, p = 0.012) and steroid use (OR = 10.14; 95%CI = 2.63–39.12, p = 0.0002). Our data suggest that R72P variant seems to be associated with high risk for development of CRC but carries low risk for development of UC. R72P genotypes might be a useful predictive marker for surgical and medical treatment of UC.
Document Type: Research Article
Affiliations: 1: School of Medicine, Department of Medical Biology, Marmara University, Tibbiye Cad., No: 49, Haydarpasa, 34668, Istanbul, Turkey 2: School of Medicine, Department of Medical Biology, Marmara University, Tibbiye Cad., No: 49, Haydarpasa, 34668, Istanbul, Turkey, Email: firstname.lastname@example.org 3: Marmara University Gastroenterology Institute, Basibuyuk, Istanbul 4: School of Medicine, Department of Pathology, Marmara University, Altunizade, Istanbul
Publication date: 2010-12-01