Genetic status of p53 in stomach cancer: Somatic mutations and polymorphism of codon 72

Belyavskaya, V. A.; Vardosanidze, V. K.; Smirnova, O. Yu.; Karakin, E. I.; Savkin, I.; Gervas, Polina; Чердынцева, Н. В.; Воевода, М. И.

doi:10.1007/s10517-006-0139-7

Cited by 21 publications

(12 citation statements)

References 8 publications

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“…Inconsistent associations were observed for tumor protein p53 (TP53) Arg73Pro, the most widely studied polymorphism. Meta-analysis of the 14 included studies showed that, overall, the Pro allele at codon 72 of TP53 was not significantly associated with GC (OR, 1.08; 95% confidence interval (CI), 0.91 -1.27) (Figure 2 15,20,26,27 and two in the Caucasian populations 16,25 ), and therefore the summarized results have to be interpreted with caution. 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.…”

Section: Resultsmentioning

confidence: 98%

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

Gao

Nieters

Brenner³

2009

Eur J Hum Genet

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Apart from Helicobacter pylori infection and lifestyle factors, host genetic susceptibility has been suggested to contribute to individual variation in gastric cancer risk as well. Aiming to evaluate the associations between host cell proliferation-related genetic polymorphisms and gastric cancer susceptibility, we reviewed the related studies published until 15 September 2008 and quantitatively summarized the associations of the most widely studied polymorphisms (TP53 Arg72Pro, L-myc EcoRI) using meta-analysis. Fifty-five eligible studies were included in this review. Twenty-three polymorphisms significantly related to gastric cancer risk in at least one study were identified. Polymorphisms determining higher levels of growth factors, which are important for tissue repair, were recently observed to be associated with reduced risk of gastric cancer. In the meta-analysis, TP53 72Pro was associated with increased risk of diffuse gastric cancer among Asians (OR, 1.44; 95% CI, 1.04-1.99), but decreased risk of intestinal gastric cancer among Caucasians (OR, 0.56; 95% CI, 0.36-0.89). This review suggests that cell proliferation-related genetic polymorphisms could be candidate biomarkers of gastric cancer risk, but current evidence for the use for risk stratification is still very limited. Modestly significant associations in meta-analyses stratified by population or type of gastric cancer may be observed by chance because of the limited number of studies and small sample size. Larger studies are warranted to clarify the effect of cell proliferation-related genetic polymorphisms on gastric carcinogenesis.

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Section: Resultsmentioning

confidence: 98%

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

Gao

Nieters

Brenner³

2009

Eur J Hum Genet

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“…Several polymorphisms and somatic mutations in p53 have been identiWed. A common one at codon 72 of exon 4, which encodes proline (Pro) or arginine (Arg), has been reported to aVect the risks of many types of cancer especially of lung cancer (Agorastos et al 2004;Belyavskaya et al 2006;Chen et al 2000;Lee et al 2000;Weston et al 1992;Zehbe et al 2001). Although many studies have reported the Pro allele at codon 72 was a risk factor for developing lung cancer (Fernandez-Rubio et al 2008;Liu et al 2001;Mechanic et al 2007;Popanda et al 2007;Sreeja et al 2008;Szymanowska et al 2006), the results are inconclusive.…”

Section: Introductionmentioning

confidence: 99%

P53 polymorphism and lung cancer susceptibility: a pooled analysis of 32 case–control studies

et al. 2009

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To explore the real association between p53 codon 72 polymorphism and lung cancer risk, a pooled analysis of 32 case-control studies involving 19,255 subjects was conducted. When all 32 studies were pooled into the analysis, significantly elevated lung cancer risks were associated with variant genotypes in all genetic models (for Pro/Arg vs. Arg/Arg: OR 1.21, 95% CI 1.01-1.23; for Pro/Pro vs. Arg/Arg: OR 1.20, 95% CI 1.03-1.39; for Pro/Pro + Pro/Arg vs. Arg/Arg: OR 1.14, 95% CI 1.03-1.25; for Pro/Pro vs. Arg/Arg + Pro/Arg: OR 1.06, 95% CI 1.01-1.12). In the subgroup analysis by ethnicity, histological type, or smoking status, significantly increased risks were found in subgroups such as Asians, Caucasians, lung adenocarcinoma patients, or smokers, respectively. In conclusion, our results suggest that the Pro allele at p53 codon 72 is emerging as a low-penetrance susceptibility allele for lung cancer development.

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“…Chung et al [10] reported frequent polymorphism at codon-72 and suggested that the Pro/Pro genotype was associated with proximal cancer and Arg/Arg genotype with distal cancer. Mutation at codon-72, exon-4 of p53 was also reported in gastric cancer patients by Belyavskaya et al [6], Yi and Lee [11], Cañas et al [12], and many other studies. It is worthy to mention that mutation at codon-72, exon-4 of p53 has also been reported not to be associated with gastric carcinoma in different populations [13,14].…”

Section: Introductionmentioning

confidence: 56%

“…More than 50% of human cancers contain a mutation of the p53 gene [4]. Many somatic and germ line p53 mutations lead to a loss of p53 function have been detected in gastric cancer patients [5,6]. Kirsten rat sarcoma viral oncogene homolog (K-RAS) is an important regulator in many signal transduction pathways.…”

Section: Introductionmentioning

confidence: 99%

Genetic mutations of p53 and k-ras in gastric carcinoma patients from Hunan, China

Chen

Rao

et al. 2010

Tumor Biol.

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This case-control study investigated the mutations in p53 and k-ras genes of 123 gastric carcinoma patients and 129 normal individuals from Hunan, China. By isolating genomic DNA from peripheral blood and employing polymerase chain reaction-single strand conformation polymorphism and DNA sequencing, the mutations of p53 exons-5, 6, 7, and 8 and k-ras were detected. The overall mutation frequency of p53 was 29.3%, and mutation was found in all four exons studied. The point mutations were predominant and among them, G:C→A:T was the highest (41.7%), followed by A:T→G:C (25%), G:C→C:G (11.1%), G:C→T:A (8.3%), and A:T→T:A (2.8%). The frameshift mutation was 11.1%. Mutations were detected in codons-131, 132, 133, 135, 149, 151, 162, 167, 173, 174, and 175 of exon 5, codons-193, 197, 213, and 215 of exon 6, codons-245, 246, 248, 249, and 270 of exon 7, and codons-271, 272, 273, and 282 of exon 8 of p53. The overall frequency of mutation in k-ras was 9.8%, mostly in codon-12 (91.7%) and in codon-13 (8.3%). There was no significant relationship between p53 and k-ras gene mutation in gastric carcinoma patients. Also, the relationships between p53 mutation and age, sex, smoking or drinking, and tumor metastasis were not significant. However, the patients with high/high-middle differentiated gastric carcinoma had a higher association with of p53 mutations. This study identified some novel p53 mutations in gastric cancer and showed mutation pattern and frequency of p53 and k-ras in the population of the central southern region of China.

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Genetic status of p53 in stomach cancer: Somatic mutations and polymorphism of codon 72

Cited by 21 publications

References 8 publications

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

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

P53 polymorphism and lung cancer susceptibility: a pooled analysis of 32 case–control studies

Genetic mutations of p53 and k-ras in gastric carcinoma patients from Hunan, China

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