A TP53 polymorphism is associated with increased risk of colorectal cancer and with reduced levels of TP53 mRNA

Gemignani, Federica; Moreno, Vı́ctor; Landi, Stefano; Moullan, Norman; Chabrier, Amélie; Gutiérrez‐Enríquez, Sara; Hall, Janet; Guinó, Elisabet; Peinado, Miguel A.; Capellà, Gabriel; Canzian, Federico

doi:10.1038/sj.onc.1207305

Cited by 193 publications

(189 citation statements)

References 13 publications

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“…We observed no association between intron 3 and intron 6 polymorphisms and oral cancer risk. Recent researches suggest that intronic polymorphisms may affect the function of wild type p53 protein and hence cancer risk (Avigad et al, 1997;Lehman et al, 2000;Gemignani et al, 2004). However, in cell culture analysis, these two intronic polymorphisms (16 bp duplication in intron 3 and G>A in intron 6) did not seem to be sufficient to impair p53 function during the neoplastic transformation but required an additional coding region mutation.…”

Section: Discussionmentioning

confidence: 99%

“…Wu et al (2002) have reported low apoptotic index and less repair capacity of lymphoblastoid cell lines that harbor A2 and A alleles of intron 3 and intron 6 polymorphisms, respectively. Gemignani et al (2004) have also found that 16 bp duplication in intron 3 reduced the mRNA level of p53 but because of strong linkage disequilibrium between intron 3 and exon 4 polymorphism, it remains to be determined that whether intron 3 alone influence mRNA stability or need the presence of exon 4 polymorphism. Overall, the functional role of these 2 intronic polymorphisms of p53 in cancer risk remains uncertain.…”

Section: Discussionmentioning

confidence: 99%

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Association between p53 Gene Variants and Oral Cancer Susceptibility in Population from Gujarat, West India

Patel

Vajaria²,

Begum³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: p53 gene variants i.e. 16 bp duplication in intron 3, Arg72Pro in exon 4 and G>A in intron 6 have been reported to modulate susceptibility to various malignancies. Therefore, the present study evaluated the role of these p53 polymorphisms in oral cancer susceptibility in a population from Gujarat, West India. Method: Genotype frequencies at the three p53 loci in 110 controls and 79 oral cancer cases were determined by the PCR-RFLP method. Results: Heterozygous individuals at exon 4 showed protection from developing oral cancer. Homozygous wild and heterozygous individuals at intron 3 and those heterozygous at exon 4 in combination appeared to be at lowered risk. Furthermore, carriers of the 16 bp duplication allele at intron 3, proline allele at exon 4 and G allele at intron 6 were protected from oral cancer development. Conclusion: p53 polymorphisms, especially Arg72Pro in exon 4 could significantly modify the risk of oral cancer development in Gujarat, West Indian population.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Association between p53 Gene Variants and Oral Cancer Susceptibility in Population from Gujarat, West India

Patel

Vajaria²,

Begum³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…56 Recently, reduced levels of p53 mRNA has been proposed to be associated with the p53 intron 3 16 bp duplication allele. 57 Overall, the functional role of the 2 intronic polymorphisms of p53 analyzed and their modulatory role in cancer risk remain uncertain. Further studies need to be conducted to unveil any regulatory role of these intronic sequences.…”

Section: Discussionmentioning

confidence: 99%

Risk assessment of p53 genotypes and haplotypes in tobacco‐associated leukoplakia and oral cancer patients from eastern india

Mitra

Sikdar

Misra

et al. 2005

Intl Journal of Cancer

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The role of 3 p53 polymorphisms (16 bp duplication at intron 3, codon 72 Arg/Pro and intron 6 NciI RFLP at np 13494) as potential markers for indicating cancer risk remains inconclusive. In our case-control study consisting of 197 leukoplakia and 310 oral squamous cell carcinoma (SCC) patients and 348 controls, genotype frequencies at these 3 p53 loci were determined by PCR-RFLP method and analyzed by multiple logistic regression to determine the risks of the diseases. The 2/2 genotype at codon 72 of p53 was at risk for developing leukoplakia (OR 5 1.6, 95% CI 1.1-2.3), whereas the combination of 1/2 and 2/2 genotypes at intron 3 and 1/1 and 1/2 genotypes at intron 6 conferred a protective effect against leukoplakia and oral SCC development, respectively (OR 5 0.5, 95% CI 0.4-0.8 and OR 5 0.6, 95% CI 0.5-0.9, respectively). When subjects were stratified according to specific tobacco habit, the risk/protection estimates improved significantly in some cases. Specifically, the exclusive smokers with p53 codon 72 2/2 genotype showed a higher risk of developing leukoplakia (OR 5 2.7, 95% CI 1.2-6.3). Furthermore, a particular p53 haplotype 1-2-2 was at risk for both tobacco-associated leukoplakia and oral SCC (OR 5 1.5, 95% CI 1.1-1.9 and OR 5 1.3, 95% CI 1.1-1.7, respectively). Our results show that both specific p53 genotype and haplotype can indicate risk of tobacco-associated leukoplakia, but risk of development of tobacco-associated oral SCC can be predicted by specific p53 haplotype only. ' 2005 Wiley-Liss, Inc.

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“…However, it is interesting to note that the rare haplotypes (rare allele in introns 3 and 6) were slightly associated with a risk of oral cancer (OR ¼ 1.72; 95% CI, 0.97 -3.07) ( Table 2). Recently, Gemignani et al (2004) have observed that a rare allele in intron 3 was associated with an increased risk of colorectal cancer and reduced basal levels of p53 mRNA in immortalised lymphoblastoid cell lines. Taken together, these results could support the speculation by Wu et al (2002) that introns 3 and 6 rare alleles might exert a functional effect, because as the copy number of the rare allele in introns 3 and 6 is increased, the level of the apoptotic index is decreased.…”

Section: Discussionmentioning

confidence: 99%

p53 polymorphisms associated with mutations in and loss of heterozygosity of the p53 gene in male oral squamous cell carcinomas in Taiwan

Huang

et al. 2004

Br J Cancer

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The present study was designed to examine whether different p53 haplotypes of exon 4 -intron 3 -intron 6 affect the frequency of mutations and loss of heterozygosity (LOH) of the p53 gene in male oral squamous cell carcinomas (OSCCs) in Taiwan. We found that individuals without two Pro-W-G alleles had significantly higher frequency of p53 mutations than those with two Pro-W-G alleles (odds ratio (OR) ¼ 1.98; 95% confidence interval (CI), 1.10 -3.56). Out of the 172 p53 gene exon 4 informative male OSCCs, 72 (41.9%) showed LOH. Among these 72 OSCCs with LOH, the frequency of Pro allele loss was 73.6% (53/72). It is notable that alcohol drinking increased the frequency of Arg allele loss (OR ¼ 10.56; 95% CI, 1.23 -234.94) in OSCCs from patients who both smoked cigarettes and chewed areca quid (AQ). The frequency of LOH of p53 was not different between p53-mutated OSCCs and p53-normal OSCCs. Thus, the present study revealed that (a) the Arg allele is associated with p53 mutations, (b) the Pro allele is preferentially lost in OSCCs associated with cigarette smoking and AQ chewing, while the frequency of Arg allele loss is increased with alcohol drinking, and (c) haploinsufficiency of p53 is in itself likely to contribute to tumour progression in Taiwanese OSCCs.

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A TP53 polymorphism is associated with increased risk of colorectal cancer and with reduced levels of TP53 mRNA

Cited by 193 publications

References 13 publications

Association between p53 Gene Variants and Oral Cancer Susceptibility in Population from Gujarat, West India

Association between p53 Gene Variants and Oral Cancer Susceptibility in Population from Gujarat, West India

Risk assessment of p53 genotypes and haplotypes in tobacco‐associated leukoplakia and oral cancer patients from eastern india

p53 polymorphisms associated with mutations in and loss of heterozygosity of the p53 gene in male oral squamous cell carcinomas in Taiwan

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