Polymorphisms of the TP53 codon 72 and WRN codon 1367 in individuals from Northern Brazil with gastric adenocarcinoma

Abstract

Gastric cancer is the second most frequent type of neoplasia and also the second most common cause of death in the world. TP53 codon 72, which produces variant proteins with an arginine (Arg) or proline (Pro), has been reported to be associated with cancers of the lung, oesophagus, stomach and cervix. Werner's syndrome (WS) is a premature ageing disease caused by a mutation in the WRN gene. The WRN protein acts as a DNA helicase and as an exonuclease. WRN codon 1367 produces variant proteins with an Arg or cysteine (Cys). This polymorphism has been studied, in order to understand the clinical impact of the molecular variants in WS and in age-related disorders. In the present study, the TP53 codon 72 and the WRN codon 1367 polymorphisms were investigated in 54 gastric adenocarcinoma patients (31 diffuse-type and 25 intestinal-type) and 54 controls. DNA samples were extracted, and PCR-RFLP was utilised for genotyping TP53 codon 72 and WRN codon 1367. The allele frequencies of the TP53 polymorphism were: Arg=0.74 and Pro=0.26. The allele frequencies of the WRN polymorphism were: Cys=0.73 and Arg=0.27. The crude genotypic frequencies in gastric cancer patients were similar to those of the controls, but in the WRN codon 1367 polymorphisms the mean age tended to be higher in the Arg/Arg genotypes. There also was an association, although not statistically significant, between the presence of Helicobacter pylori and the genotypes Cys/Cys and Cys/Arg and a higher percentage of cardia cancer among the Arg/Arg genotypes, and of non-cardia cancer among genotypes Cys/Cys and Cys/Arg. These findings may be a reflection of differences in the interaction between WRN codon 1367 polymorphisms and local factors in the stomach. To our knowledge, this is the first study to examine a genetic polymorphism of the WRN gene in cancer. The precise mechanisms of action of the TP53 and WRN polymorphisms involved in the aetiopathogeny of this disease need further investigation.

Cell proliferation-related genetic polymorphisms and gastric cancer risk: systematic review and meta-analysis

“…One study on this polymorphism shown in Table 1 was excluded from the meta-analysis because the genotype frequencies and ORs were not reported by the original article. 24 No evident publication bias was observed as assessed by Begg rank correlation method (P ¼ 0.83) and Egger weighted regression method…”

Prognostic value of TP53 Pro47Ser and Arg72Pro single nucleotide polymorphisms and the susceptibility to gliomas in individuals from Southeast Brazil

“…Granja et al (2004), besides demonstrating an association between the Pro/Pro genotype and thyroid cancer, also reported a frequency of 0.65 for Arg72 allele in a control group from southeast Brazil. Khayat et al (2005), in a case-control study of gastric adenocarcinoma in the State of Pará, northern Brazil, described a frequency of 0.69 for Arg72 allele in their control group.…”

p 53 codon 72 polymorphism in stomach and colorectal adenocarcinomas in Iranian patients

“…[2] The p53 codon 72 Arg/Pro polymorphism has been linked to cancer susceptibility in a variety of malignant processes, notably lung cancer, however, these findings remain controversial. [3][4][5][6][7][8][9][10][11][12][13][14]19] This controversy might be due to the fact that the genotype distribution of the p53 codon 72 Arg/Pro polymorphism differs significantly with race. [19] For instance, Shepherd et al showed that Arg/ Arg genotype frequency was 64% in whites as compared to 24% in blacks.…”

“…[2] Despite the strong association of somatic p53 gene mutations with malignant processes, [2] the association of germline polymorphisms of p53 with malignancies is the subject of controversy in different ethnic backgrounds and in different types of cancer. [5][6][7][8][9][10][11][12][13][14] At least 13 polymorphisms have been described in this gene. [14] The most commonly studied one is a single nucleotide polymorphism (SNP) at codon 72 in exon 4 of the p53 gene, which results in the substitution of arginine (Arg) by proline (Pro) in the transactivating domain.…”

“…[6][7][8]13] However, other reports have failed to confirm this association. [5,[9][10][11] The discrepancies between studies may be related in part to significant differences in the genotype distribution of the p53 codon 72 among ethnic groups. [17] The role of this SNP in stomach and colorectal cancers has apparently not been investigated in Iran.…”