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.

A Review of Cancer Genetics and Genomics Studies in Africa

“…Other studies have also explored the contribution of epigenetic changes to colorectal cancer carcinogenesis in Africa ( 278 , 282 – 285 ). For example, the methylation of UCH1 and p14ARF genes were reported to drive colorectal cancer in the presence of TP53 mutation in Tunisia ( 282 , 283 , 286 , 287 ). Other studies on the North African populations reported the influence of polymorphisms in telomere and mitochondrial D-loop region on the clinicopathological characteristics of the colorectal cancers among their patients ( 288 , 289 ).…”

TP73 G4C14-A4T14polymorphism and cancer susceptibility: evidence from 36 case–control studies

“…The characteristics of these studies were showed in Table 1. Among these publications, there are 6 concerned about cervical cancer [17,34,40,50–52], 5 about lung cancer [16,29,33,35,38], 4 about colorectal cancer [28,37,46,47], 4 about esophageal cancer [14,27,28,39], 4 about gastric cancer [28,39,43,48], 3 about breast cancer [15,26,30], 3 about squamous cell carcinoma of the head and neck [32,41,45], as well as other 7 publications focus on Endometrial cancer [36], lymphoma [31], melanoma [42], nasopharyngeal carcinoma [53], neuroblastoma [25], ovarian cancer [44] and prostate cancer [49], respectively. As to the ethnicity, 14 studies were performed in Caucasians, while the other 22 studies were managed in Asian population.…”

Association between TP73 G4C14-A4T14 polymorphism and different cancer types: an updated meta-analysis of 55 case–control studies

“…However, another study failed to observe any significant association between the TP73 GC/AT variant genotype and allele distribution and clinical parameters of CRC. 30,35,42,44,57 Some previous studies identified the AC/GT genotype of G4C14-A4T14 as a significant risk factor for GCs, although other studies found no such association. 31,36,40,67,70 Decreased expression of p73 mRNA was identified in both inflammatory and noninflammatory BC cells compared with normal breast epithelial cells, indicating that this variant might increase the risk of BC by reducing the expression of p73.…”