Polymorphisms of H-ras-1 and p53 in Breast Cancer and Lung Cancer: A Meta-Analysis

Weston, Ainsley; Godbold, James

doi:10.2307/3433304

Cited by 28 publications

(30 citation statements)

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“…These changes in conjunction with certain environmental exposures (e.g., smoking, lung cancer) may increase the risk for cancer development in people with susceptible genotypes. However, these studies have been inconsistent, most likely because of a number of factors, including racial frequency differences between cases and controls, varied population bases, and lack of Hardy-Weinberg equilibrium in some examined cases (15)(16)(17)(18)(19)(20). In our opinion, these variables and others account for the discrepant results between independent studies examining the polymorphism of p53 at codon 72 and carcinogenesis.…”

Section: Discussionmentioning

confidence: 84%

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Polymorphism at Codon 72 of p53 Is Not Associated with Cervical Cancer Risk

et al. 2000

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P53 allelic polymorphism at codon 72 has been studied as a possible predisposing factor for cervical carcinogenesis with inconsistent results. Storey and colleagues recently published the interesting finding of a 7-fold increased risk for cervical cancer in women homozygous for the arginine allele at codon 72. This stimulated a number of independent investigations, the majority of which found no association of cervical cancer and arginine homozygosity.With the use of a modified Storey method for determining codon 72 allelotypes, DNA was examined from 431 microdissected, formalin-fixed, archival cervical conization specimens ranging from low-grade squamous lesions to invasive cancer. An alternative independent method using restriction fragment length polymorphism analysis was performed on all arginine homozygotes and all indeterminate cases for confirmation and final allelotype assignment.With the use of Storey's method alone, logistic regression suggested an association (odds ratio, 1.42) between arginine homozygosity and invasive disease. However, with the use of the combined method for accurate allelotyping, this trend disappeared (odds ratio, 1.00), the discordance was clearly resolvable as being due to methodologic variables.With the use of two separate methods for codon 72 allelotyping and accounting for a number of the issues raised in previously published reports, there is no increased risk for invasive cervical cancer associated with arginine homozygosity at codon 72 of p53.KEY WORDS: Cervix, Neoplasia, p53, Papillomavirus, Polymorphism.Mod Pathol 2000;13(4):373-378Human papillomaviruses (HPVs) are epitheliotropic double-stranded DNA viruses that have been implicated in cervical carcinogenesis. More than 100 HPV genotypes have been identified. Traditionally, HPV genotypes, which are frequently identified in cervical neoplasms, have been segregated into those with a low risk and those with a high risk for malignant transformation. HPV types 6 and 11 are the prototypes of low-risk viruses that are most frequently found in low-grade squamous intraepithelial lesions (LSIL) and condylomata. HPV 16, 18, 31, and 45 account for approximately 80% of invasive cervical carcinomas, and the HPV 16 -related group is overrepresented in high-grade squamous intraepithelial lesions (HSIL) and squamous cancers compared with the HPV 18 -related viruses. The expression of HPV mRNA and proteins provides a coherent model for cervical carcinogenesis (1-3). Within the HPV genomes, the E6 and E7 genes are the driving forces behind epithelial proliferation and transformation. These transcribed genes are conserved and expressed within all HPV-infected pathologies. In many high-risk cervical dysplasias and invasive carcinomas, the E6 and E7 proteins are restrictively transcribed from the HPV genome integrated into the host DNA (4 -6). The link between oncogenesis and the transforming properties of HPV infection was identified by the interaction between these proteins and host cellular tumor suppressor gene products. Specifically, E7...

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Section: Discussionmentioning

confidence: 84%

“…Ethnic differences in these allelic frequencies exist as well (14). In the U.S. population, the proline allele is identified more commonly in African Americans (61%) than in Caucasians (34%) (13)(14)(15).…”

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confidence: 99%

Polymorphism at Codon 72 of p53 Is Not Associated with Cervical Cancer Risk

et al. 2000

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“…Although biochemically different, the significance of the p53 codon 72 polymorphism remains controversial in terms of cancer epidemiology. Significant association between the codon 72 polymorphism and risk of cancer had been reported, although the results with regard to most cancer diseases, including breast cancer, remain inconclusive (7)(8)(9). Nonetheless, it is possible that the differences between various reports can reflect the populations that were analyzed, as there are inherent differences in the relative prevalence of the polymorphic alleles in various populations (10).…”

Section: Introductionmentioning

confidence: 82%

Evidence for Selective Expression of the p53 Codon 72 Polymorphs: Implications in Cancer Development

Siddique

Chowbay²,

Fiszer-Maliszewska

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Polymorphism at codon 72 of p53 results in either the arginine or proline form of p53, whose functional significance in carcinogenesis is controversial. We have investigated if the expression of these p53 polymorphs is selectively regulated, using mRNA from peripheral blood of healthy Asian (Chinese) and the Caucasian (Polish) arginine/proline (arg/pro) heterozygote subjects. Asians were found to preferentially express the pro allele whereas the Caucasians preferentially express the arg allele. On the contrary, about 75% of the heterozygote Chinese breast cancer patients preferentially expressed the arg allele, which rarely contained any somatic mutations. Moreover, histologically normal tissues from Chinese heterozygote breast cancer patients showed selective expression of the arg allele, in contrast to the preferential expression of the pro allele in heterozygote healthy normal breast tissues. Together, the data suggest that the expression of the different p53 polymorphs is selectively regulated in different ethnic populations, and that the arg allele is activated during cancer development in Asians. Thus, the expression status of the p53 polymorphs, rather than the genotypic status, might be a useful indicator for cancer susceptibility. (Cancer Epidemiol Biomarkers Prev 2005;14(9):2245 -52)

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“…By contrast, the Trp53 72R allele was preferentially expressed in most heterozygote breast cancer patients . These data, together with the many reports indicating that the Trp53 72R was associated with cancer predisposition (Sja¨lander et al, 1996;Weston and Godbold, 1997;Papadakis et al, 2000;Bergamaschi et al, 2003), suggested to us that although the Trp53 72R form might be capable of inducing apoptosis better, it might not be efficient in preventing cancer formation. We have therefore investigated if the two different Trp53 variants would have differential ability to regulate DNA-repair, a process that is regulated by Trp53 and that is essential for the prevention of accumulation of genomic instability and hence, cancer formation (Risinger and Groden, 2004;Sengupta and Harris, 2005 (Figure 1a), excluding the possibility that differential expression may account for the observed transactivation differences.…”

Section: P -Expressing Cells Exhibit Reduced Micronuclei Formation mentioning

confidence: 88%