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 Fatih Eren & Mustafa Akkiprik & Özlen Atuğ & Özgür Sönmez & Gülgün Tahan & Filiz Özdemir & Hülya Över Hamzaoğlu & Çiğdem Ataizi Çelikel & Neşe İmeryüz & Erol Avşar & Ayşe Özer Received: 13 April 2009 / Accepted: 24 February 2010 / Published online: 23 March 2010 # Arányi Lajos Foundation 2010 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 polymor- phism 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 develop- ment 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. Keywords p53 . Codon 72 polymorphism . Colorectal cancer . Ulcerative colitis . Colectomy . Steroid . Family history Introduction Apart from point mutations, polymorphic variants in the TP53 (geneID: 7157) locus might determine its function and cancer-related phenotypical effects. The polymorphism at codon 72 encodes either an arginine amino acid (Arg/ 72R) or a proline residue (Pro/72P) and localizes on exon 4 in the polyproline domain. Mutation of the domain is not a common location in tumor, but this domain is essential for apoptotic response and inhibition of tumorogenesis [1, 2]. Functional analysis studies show that R72P polymorphism changes p53 protein properties by different ways and plays a pivotal role in cancer development [3]. The polymorphism has potential modifier capacity of mutant p53 protein [4], and also determines transcript levels of p53 [5]. Arginin allele of codon 72 has been found to be a more potent inducer of apoptosis than proline allele [6]. Clinically, R72P polymorphism might affect prognosis and response to Fatih Eren and Mustafa Akkiprik contributed equally to this work. F. Eren : M. Akkiprik (*) : Ö. Sönmez : A. Özer School of Medicine, Department of Medical Biology, Marmara University, Tibbiye Cad., No: 49, Haydarpasa, 34668 Istanbul, Turkey e-mail: akkiprik@yahoo.com F. Eren : Ö. Atuğ : G. Tahan : F. Özdemir : H. Ö. Hamzaoğlu : N. İmeryüz : E. Avşar Marmara University Gastroenterology Institute, Basibuyuk, Istanbul Ç. A. Çelikel School of Medicine, Department of Pathology, Marmara University, Altunizade, Istanbul Pathol. Oncol. Res. (2010) 16:563–568 DOI 10.1007/s12253-010-9255-9