Correlation between human papillomavirus-associated cervical cancer and p53 codon 72 arginine/proline polymorphism

Tachezy, Ruth; Mikysková, I; Saláková, Martina; Ranst, Marc Van

doi:10.1007/s004390051146

Cited by 15 publications

(13 citation statements)

References 9 publications

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“…Storey et al [1998] showed that women homozygous for the Arg allele were more susceptible to develop cervical cancer than Arg/Pro heterozygous or Pro/Pro homozygous women and concluded therefore that this polymorphism might be involved in cervical carcinogenesis. However, our study shows that there is no increased risk concerning Arg/Arg genotype in the different cytological categories (P ¼ 0.336), in agreement with the most recently studies including those that used blood [Hayes et al, 1998;Kim et al, 2001;Humbey et al, 2002;Santos et al, 2005] or exfoliated cervical cells [Klaes et al, 1999;Tachezy et al, 1999;Tenti et al, 2000;Abba et al, 2003].…”

Section: Discussionsupporting

confidence: 94%

The p53 R72P polymorphism does not influence cervical cancer development in a portuguese population: A study in exfoliated cervical cells

Oliveira

Sousa

Santos

et al. 2008

Journal of Medical Virology

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The interaction between the E6 protein of the high-risk human papillomaviruses (HPVs) with p53 seems to be crucial in cervical carcinogenesis. The presence of Arg/Arg genotype at codon 72 of TP53 gene was characterized as a risk factor in development of cervical cancer. However, the role of this polymorphism remains controversial and some authors suggested that the origin of DNA (blood or exfoliated cervical cells) might influence these results. This study analyzed the effect of the p53 codon 72 polymorphism (R72P) in exfoliated cervical cells of women from the northern region of Portugal using two methodologies: allele-specific polymerase chain reaction and real-time polymerase chain reaction. We studied 700 cervical exfoliated cells which showed: 334 cases from women without cervical cancer or cervical lesion (N), 114 low-grade squamous intraepithelial lesions (LSIL), 107 high-grade squamous intraepithelial lesions (HSIL), 20 invasive cervical cancers (ICC) and 125 atypical squamous cells of unknown significance (ASCUS). No statistically significant differences between cases and controls were found, regarding the influence of the R72P polymorphism with cytological classification, high risk-HPV infection and HPV16 presence (P = 0.336, P = 0.945, and P = 0.964, respectively). Also, the influence of this polymorphism in the median age of onset for LSIL, HSIL, and ICC was not statistically significant (P = 0.674, P = 0.810, and P = 0.928, respectively). Therefore, the hypothesis that women with Arg/Arg genotype have an increased risk of developing cervical cancer failed to be proven in this study. Moreover, our study reveals that results using exfoliated cervical cells are reliable as compared with studies on blood.

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Section: Discussionsupporting

confidence: 94%

The p53 R72P polymorphism does not influence cervical cancer development in a portuguese population: A study in exfoliated cervical cells

Oliveira

Sousa

Santos

et al. 2008

Journal of Medical Virology

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“…One of the most studied polymorphism is the aminoacidic variation p.Arg72Pro within the exon 4 (rs1042522:C4G), which results in a structural alteration of the protein [Pietsch et al, 2006]. The rs1042522:C4G polymorphism was associated with a higher risk of oral, nasopharyngeal, lung, thyroid, skin, cervical, prostate, bladder, gastric, colorectal, and hepatic tumors [Cenci et al, 2003;Comar et al, 2004;Ezzikouri et al, 2007;Fan et al, 2000;Granja et al, 2004;Huang et al, 2003Huang et al, , 2004Kietthubthew et al, 2003;Koushik et al, 2004;Li et al, 2004;Makni et al, 2000;Miller et al, 2002;Mitra et al, 2005;Nan et al, 2008;Perez et al, 2006;rbel-Alon et al, 2002;Shen et al, 2002;Sotamaa et al, 2005;Soulitzis et al, 2002;Starinsky et al, 2005;Szymanowska et al, 2006;Tachezy et al, 1999;teenyi-Agaba et al, 2004;Tiwawech et al, 2003;Twu et al, 2006;Whibley et al, 2009;Yang et al, 2001;Zhou et al, 2007]. Previous studies have suggested differences in the function of p53 depending on the codon 72 allele present.…”

Section: Introductionmentioning

confidence: 98%

ΔN133p53 expression levels in relation to haplotypes of the TP53 internal promoter region

Bellini¹,

Pitto²,

Marini³

et al. 2010

Hum. Mutat.

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The transcription of the DeltaN133p53 isoform of the TP53 gene is controlled by an internal promoter region (IPR) containing eight polymorphisms in 11 common haplotypes, following a resequencing of 47 Caucasians. We assayed the functional effects of the commonest six haplotypes on the promoter activity with a luciferase reporter system, in HeLa and 293T cells. These studies showed that different IPR haplotypes are associated with differences in the promoter activity resulting in marked variation in the baseline expression of DeltaN133p53. In vivo quantitative-polymerase chain reaction (PCR) on human tissues confirmed that the baseline levels of DeltaN133p53 showed haplotype specific differences that paralleled those seen in vitro. When cell lines were treated with camptothecin, the fold-increase in DeltaN133p53 levels was dose-dependent but haplotype-independent (i.e., similar for all the haplotypes). Finally, we used an electrophoretic mobility shift assay to analyze the rs1794287 polymorphism and found changes in the pattern of protein binding. This partially confirmed our in silico analysis showing that the polymorphism rs1794287 can affect the function of the internal promoter by changing its affinity for several transcription factors. Thus, we showed that the expression of DeltaN133p53 is under genetic control, and suggested the presence of interindividual differences underlying this mechanism.

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“…Consequently, these authors noted that, in the United Kingdom, individuals homozygous for the arginine allele were about seven times more susceptible to HPV-associated tumorigenesis than proline/ arginine heterozygotes. Subsequent studies in several countries (Rosenthal et al, 1998;Lanham et al, 1998;Minaguchi et al, 1998;Hayes et al, 1998;Helland et al, 1998;Josefsson et al, 1998; Hildesheim et BR SHORT -COMMUNICATION al., 1998;Ngan et al, 1999;Tachezy et al, 1999;Dybikowska et al, 2000;Klug et al, 2001;Suárez-Rincon et al, 2002) failed to confirm this association, leading to the suspicion that in the process of HPVassociated tumorigenesis due to genotype differences at the codon 72 of p53, other factors in addition to these isoforms of p53 are important as risk factors for the development of cervical cancer.…”

Section: Introductionmentioning

confidence: 99%

p53 Codon 72 Polymorphism and Risk of Cervical Cancer

Ojeda¹,

Ampuero²,

Rojas

et al. 2003

Biol. Res.

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implicated the proline/argine polymorphism of the codon 72 of the tumor-suppressor gene p53 in the development of cervical cancer (CC) with the observation that the p53 protein is more efficiently inactivated by the E6 oncoprotein of human papillomavirus in p53 arginine as compared with its proline isoform. These authors further noted that in the United Kingdom, individuals homozygous for the arginine allele were several times more susceptible to HPV-associated tumorigenesis that proline/arginine heterozygotes. Subsequent studies in different countries failed to unanimously confirm this association. Motivated by the high incidence of CC in Chile, we undertook a case control study obtaining the following frequencies for genotypes PP, AP and AA in 60 ICC cases and 53 carefully selected controls: 0.067, 0.250, 0.683 and 0.075, 0.453, 0.472 respectively. A significant difference (X 2 = 3.19 p < 0.02) and an odds ratio of 2.62 supported Storey et al (1998)'s results. In addition, rejecting previous hypotheses about the world distribution of the p53 codon 72 polymorphism, we conclude that this distribution most likely represents ancient human dispersal routes. Several methodological and biological explanations for the results obtained in previous negative association studies are briefly discussed.

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Correlation between human papillomavirus-associated cervical cancer and p53 codon 72 arginine/proline polymorphism

Cited by 15 publications

References 9 publications

The p53 R72P polymorphism does not influence cervical cancer development in a portuguese population: A study in exfoliated cervical cells

The p53 R72P polymorphism does not influence cervical cancer development in a portuguese population: A study in exfoliated cervical cells

ΔN133p53 expression levels in relation to haplotypes of the TP53 internal promoter region

p53 Codon 72 Polymorphism and Risk of Cervical Cancer

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