title: Association of a p73 exon 2 GC/AT polymorphism with colorectal cancer risk and survival in Tunisian patients.
abstract: We examined the association of one linked GC/AT polymorphism at p73 with the risk of colorectal cancer. In the present study, we investigated whether this polymorphism was related to the risk of colorectal cancer, and whether there were relationships between the polymorphism and LOH, protein expression or clinicopathological variables. The p73 genotypes were determined by PCR-restriction fragment length polymorphism in 150 Tunisians patients with colorectal cancer and in 204 healthy control subjects. Immunohistochemistry was performed on normal mucosa, primary tumour and metastasis. The frequencies of the genotypes were 52% for wild-type (GC/GC), 31% for heterozygotes (GC/AT) and 17% for variants (AT/AT) in patients, and 54%, 35% and 11% in controls, respectively. There were no significant differences of the frequencies of the three genotypes between the patients and controls (p = 0.11). We did not find any relationship of the genotypes with clinicopathological features of patients. We found that patients with the AT/AT genotype had a significantly worse clinical outcome than those with the GC/AT and GC/GC genotype. There were no significant differences between tumoural immunostaining of the total p73 and p73 polymorphism (p = 0.16). However, we found a significant difference between the expression profile of DeltaNp73 isoform and frequencies of the three genotypes (p = 0.0001). No LOH was observed at p73 locus. Our results suggest that the AT/AT genotype is significantly associated with poor prognosis in colorectal cancer. All these findings suggest that p73 polymorphism analysis may provide useful prognostic information for colorectal cancer patients.
authors.affiliation: Laboratory of Colorectal Cancer Research UR03ES04, Science University Tunis, Tunis, Tunisia. arfaouiamira@hotmail.com
authors.forename: Amira Toumi
authors.initials: AT
authors.lastname: Arfaoui
authors.forename: Lilia Ben Mahmoud
authors.initials: LB
authors.lastname: Kriaa
authors.forename: Olfa El Amine
authors.initials: Oel A
authors.lastname: El Hadj
authors.forename: Majid A
authors.initials: MA
authors.lastname: Ben Hmida
authors.forename: Myriam
authors.initials: M
authors.lastname: Khiari
authors.forename: T
authors.initials: T
authors.lastname: Khalfallah
authors.forename: Lasaad
authors.initials: L
authors.lastname: Gharbi
authors.forename: Sabeh
authors.initials: S
authors.lastname: Mzabi
authors.forename: Sadaa
authors.initials: S
authors.lastname: Bouraoui
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019656:Loss of Heterozygosity; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D014416:Tunisia
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human