Prognostic Significance of p53 Codon 72 Polymorphism Differs with Race in Colorectal Adenocarcinoma

Abstract

Purpose Several studies have examined the prognostic value of the codon 72 polymorphism of the p53 gene in colorectal adenocarcinoma, but none have addressed patient race/ethnicity. Therefore, this study assessed the prognostic value of this polymorphism in African American and Caucasian colorectal adenocarcinoma patients separately. Experimental Design Colorectal adenocarcinomas from137 African Americans and 236 non-Hispanic Caucasians were assessed for p53 mutations and genotyped for the codon 72 polymorphism. The phenotypes were correlated with p53 mutational status, clinicopathologic features, and patient survival using the χ2 test and Kaplan-Meier and Cox regression models. Results The incidence of p53 mutations was similar in African American and Caucasian patients (50% versus 54%, respectively); however, the homozygous Pro72 allele frequency was higher in African Americans (17%) as compared with Caucasians (7%). In contrast, the homozygous Arg72 allele frequency was higher in Caucasians (36%) than in African Americans (19%). In African Americans but not Caucasians, the Pro/Pro phenotype significantly correlated with a higher incidence of missense p53 mutations and with nodal metastasis. African Americans, but not Caucasians, with the Pro/Pro phenotype had significantly higher mortality (log-rank P = 0.005 versus. P = 0.886) and risk of death due to colorectal adenocarcinoma (hazard ratio, 2.15; 95% confidence interval, 1.02-4.53 versus hazard ratio, 1.60; 95% confidence interval, 0.69-3.18) than those with the phenotype Arg/Arg orArg/Pro. Conclusions The higher frequency of the Pro/Pro phenotype of p53 in African American patients with colorectal adenocarcinoma is associated with an increased incidence of p53 mutations, with advanced tumor stage, and with short survival.

Association of EGF and p53 gene polymorphisms and colorectal cancer risk in the Slovak population

“…Previous studies have implicated that both Arg and Pro alleles may be associated with the higher risk of malignancy. The risk of tumour progression in CRC patients considerably vary between racial and ethnic groups [6,13,17,18]. We found that frequency of genotype …”

“…A common SNP, referred to as Arg72Pro, is located in the proline-rich region in exon 4 in the segment of p53 [5] and encodes either an arginine amino acid (CGC, Arg72) or a proline residue (CCC, Pro72). This region is required for the growth suppression and apoptosis mediated by p53 but not for cell cycle arrest [6]. Arg72 form of p53 is a more efficient inducer of apoptosis than Pro72, and thus may increase the responsiveness to chemotherapy [7][8][9].…”

“…Pro72 is more efficient in transactivating p21 and inducing cell cycle arrest [10]. The earlier studies have reported a controversal results about the association between Pro72Pro mutant phenotype and the CRC [6,[11][12][13][14][15][16][17][18]. These discrepancies have been suggested to be due to the race-specific effects, as the Pro has been ancestral allele (~ 95% allele frequence in Africans), and the frequency of the Arg allele progressively increased as populations migrated further North [19][20].…”

Helicobacter pylori Infection and a P53 Codon 72 Single Nucleotide Polymorphism: a Reason for an Unexplained Asian Enigma

“…Of these, the codon 72 polymorphism (rs1042522) is by far the more common, which results in the substitution of arginine (Arg) by proline (Pro) in the transactivating domain.54Changes in its amino acid sequence can alter the ability of p53 to bind to receptors in target genes, alter DOI:http://dx.doi.org/10.7314/APJCP.2014.15.21.9171 Helicobacter pylori Infection and a P53 Codon 72 SNP: a Reason for an Unexplained Asian Enigma recognition motifs for post-translational modifications or alter p53 stability and interactions with other proteins (Walker and Levine, 1996;Thomas, 1999;Shepherd et al, 2002;Bergamaschi et al, 2003;Li and Prives, 2007). Such changes may contribute to tumor progression and a poor prognosis (Katkoori et al, 2009).…”

TP53 Gene Polymorphisms in Cancer Risk: The Modulating Effect of Ageing, Ethnicity and TP53 Somatic Abnormalities

“…Racespecific differences in the frequency of TP53 alterations have been shown between colorectal patients of Afro-American and Caucasian origin, with the prevalence of mutations in the former, which were rs1042522 CC carriers. Surprisingly, the African American CC genotype was associated with a high risk of lymph node metastasis and increased mortality (Katkoori et al, 2009). Although the above evidence is small in number and needs further approval, calculation of the ethnic component is essential to perform accurate and qualitatively correct association studies.…”