Codon 72 polymorphism of p53 and its association with cervical cancer

Zehbe, Ingeborg; Voglino, Gianfranco; Wilander, Erik; Genta, Franco Tarro; Tommasino, Massimo

doi:10.1016/s0140-6736(99)01914-5

Cited by 116 publications

(77 citation statements)

References 5 publications

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“…The R72 variant is also more susceptible than the 72P variant to degradation induced by human papillomavirus E6 protein, which may result in an increased susceptibility to human papillomavirus -induced tumors in homozygous R72 individuals (4). Some studies report an overrepresentation of the R72 variant in cervical cancers compared with control samples (5,6), whereas a larger meta-analysis study did not find such an association (7).…”

mentioning

confidence: 98%

Breast Cancer Patients with p53 Pro72 Homozygous Genotype Have a Poorer Survival

Tommiska

Eerola

Heinonen

et al. 2005

Clinical Cancer Research

149

130

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Purpose: The p53 R72P polymorphism has been suggested to play a role in many cancers, including breast cancer. Our aim was to evaluate association of R72P with breast cancer risk as well as histopathologic features of the breast tumors and survival. Experimental Design: The germ line R72P genotype was defined among 939 Finnish familial and 888 unselected breast cancer patients and 736 healthy population controls. The clinical and biological variables were tested for association by univariate analysis and the effects of several variables on survival by Cox's proportional hazards regression model. Results: The distribution of the genotypes was similar in all groups studied, suggesting no association with breast cancer risk. Unselected breast cancer patients with 72P homozygous genotype presented significantly more often with lobular carcinoma, whereas R72 allele carriers had a significantly higher frequency of ductal carcinomas (P = 0.004). No significant association with other histopathologic variables, like tumor grade, hormone receptor status (estrogen and progesterone receptors), or tumor-node-metastasis stage, was observed. Survival analysis showed that unselected breast cancer patients with 72P homozygous genotype had significantly poorer survival than patients with other genotypes (P = 0.003). This effect on survival was independent of p53 expression in the tumors and multivariate analysis showed that 72P homozygous genotype was overall an independent prognostic factor (risk ratio of death, 2.1; 95% confidence interval, 1.4-3.3; P = 0.001). Conclusions: These results suggest no effect of either R72P allele on breast cancer risk but a significantly reduced survival for 72P homozygous breast cancer patients. The finding of codon 72 genotype as an independent prognostic marker for breast cancer warrants further studies.

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mentioning

confidence: 98%

Breast Cancer Patients with p53 Pro72 Homozygous Genotype Have a Poorer Survival

Tommiska

Eerola

Heinonen

et al. 2005

Clinical Cancer Research

149

130

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“…What is more, it has been repeatedly demonstrated that the carriers of the R variant of the P72R polymorphism and especially the RR homozygotes were overrepresented (not underrepresented, as could be expected) in study groups with hPV-associated tumours (cervical carcinoma, Scchn) compared with the normal population, regardless of the smoking status (the latter being regarded as a major environmental risk factor for HPV-related carcinogenesis) (7,18,21). The finding of higher percentage of RR homozygotes, however, was found to be correct for true carcinoma only and not for precancerous highgrade cin (37).…”

Section: Hpv Hasmentioning

confidence: 67%

HPV Has Left the Building—the Absence of Detectable HPV DNA and the Presence of R Allele/S for the P72R Polymorphism in theTP53Gene May Call for More Aggressive Therapeutic Approach in HPV-Associated Tumours

Petkova¹,

Chelenkova²,

Yemendzhiev

et al. 2013

Biotechnology & Biotechnological Equipment

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“…Outros autores associaram o genótipo Arg/Arg p53 a aumento de 20% no risco para câncer cervical quando comparado com o genótipo Arg/Pro. Esta associação parece biologicamente plausível, uma vez que foi demonstrado que a proteína E6 do HPV 16 e 18 reconhece e leva à degradação preferencialmente a variante Arg/Arg da p53 2,[14][15][16] . No presente estudo, encontramos freqüên-cias similares dos genótipos Arg/Arg entre os grupos pesquisados: 60% no grupo com câncer, 50% no grupo com HSIL, 45,8% no grupo com LSIL e 45,2% no grupo controle.…”

Section: Discussionunclassified

Associação entre o polimorfismo no códon 72 da p53 e as lesões pré-malignas e malignas cervicais

Anschau¹,

Schmitt²,

Gonçalves³

et al. 2005

Rev. Bras. Ginecol. Obstet.

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Objetivos: testar a hipótese de que o polimorfismo no códon 72 do gene TP53 é fator de risco para as lesões pré-malignas e malignas cervicais associadas ou não ao papilomavírus humano (HPV). Métodos: foram incluídas amostras de cérvice uterina, para pesquisa de DNA de HPV e do polimorfismo no códon 72 da p53 com o uso da reação em cadeia da polimerase (PCR), de 155 pacientes que se submeteram à biópsia cervical. Foram formados três grupos de acordo com o diagnóstico histológico: lesão escamosa intra-epitelial de baixo grau (LSIL), lesão escamosa intra-epitelial de alto grau (HSIL) e carcinoma cervical. Aquelas pacientes sem alterações displásicas, citológicas e histológicas, foram consideradas controles. Para testar a associação entre o polimorfismo no códon 72 do gene TP53 e os grupos, foi utilizado o teste de χ 2 . Considerou-se como significativo o intervalo de confiança no nível de 95% (α=0,05). Resultados: quarenta pacientes tiveram o diagnóstico histológico de carcinoma cervical, 18 tinham HSIL, 24 tinham LSIL e 73 foram consideradas controles. O genótipo Arg/Arg p53 foi encontrado em 60,0% das pacientes com câncer, 50,0% dos casos com HSIL, 45,8% dos casos com LSIL e em 45,2% dos controles. Não houve diferença significativa entre as proporções de cada genótipo da p53 nos diferentes grupos independente da presença do HPV (χ 2 : 3,7; p=0,716). Conclusões: nossos dados não suportam a hipótese de que o polimorfismo no códon 72 do gene TP53 é importante no desenvolvimento de lesões cervicais pré-malignas e malignas associadas ou não ao HPV. PALAVRAS-CHAVE:Proteína p53; Polimorfismo; Neoplasias do colo uterino; Papillomavirus humano; Condições pré-cancerosas ABSTRACT Purpose: to test the hypothesis that gene TP53 codon 72 polymorphism is a risk factor for premalignant and malignant cervical lesions associated or not with human papillomavirus (HPV). Methods: uterine cervical samples were collected for HPV DNA and TP53 codon 72 polymorphism tests from 155 patients who underwent cervical biopsy. Three groups were formed according to histological diagnosis: low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and cervical carcinoma. Subjects without cytological and histological displasic changes were considered controls. To verify the association between the gene TP53 codon 72 polymorphism and the groups, the χ 2 test was applied. Confidence interval was considered significant at 95% (α=0.05). Results: forty subjects were found to present cervical carcinoma, 18 had HSIL, 24 had LSIL and 73 were grouped as controls. The genotype Arg/Arg p53 was found in 60% of the patients with cancer, in 50.0% of the cases with HSIL, 45.8% with LSIL, and in 45.2% of the controls. No significant differences were identified in the frequencies of p53 genotype between all groups, independently of the presence of HPV (χ 2 : 3.7; p=0.716). Conclusions: our data do not support hypothesis that the gene TP53 codon 72 polymorphism is important for the development of pre-malignant and malignant c...

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Codon 72 polymorphism of p53 and its association with cervical cancer

Cited by 116 publications

References 5 publications

Breast Cancer Patients with p53 Pro72 Homozygous Genotype Have a Poorer Survival

Breast Cancer Patients with p53 Pro72 Homozygous Genotype Have a Poorer Survival

HPV Has Left the Building—the Absence of Detectable HPV DNA and the Presence of R Allele/S for the P72R Polymorphism in theTP53Gene May Call for More Aggressive Therapeutic Approach in HPV-Associated Tumours

Associação entre o polimorfismo no códon 72 da p53 e as lesões pré-malignas e malignas cervicais

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