Linking TP53 codon 72 and P21 nt590 genotypes to the development of cervical and ovarian cancer.
ABSTRACT TP53 and its downstream effector gene P21 are two important genes in cell cycle regulation. Genetic alterations on p53 and attenuation of p21 expression result in progression through cell cycle G1 checkpoint, which can lead to cancer development. We analysed the frequency of TP53 codon 72 and 3'UTR P21 polymorphisms in 681 blood samples from 371 cervical cancer patients, 122 ovarian cancer patients and 188 healthy controls using AS-PCR and PCR-RFLP. Approximately twofold increased risk of ovarian cancer (OC) was observed for TP53 Pro carriers (P = 0.038), with a significantly higher risk for advanced OC (P = 0.018). Furthermore, among the P21 CC genotypes, TP53 P allele was also associated with a twofold increased risk of OC (P = 0.014) and to a threefold increased risk for advanced OC (P = 0.003) with an attributable proportion of 44.2%. These results were confirmed in an age-adjusted logistic regression analysis. No association was found between these polymorphisms and cervical cancer. Our results suggest that the TP53 codon 72 genotypes may be considered as a molecular marker, contributing to a genetic profile for ovarian cancer in women.
Article: A comprehensive review on host genetic susceptibility to human papillomavirus infection and progression to cervical cancer.[show abstract] [hide abstract]
ABSTRACT: Cervical cancer is the second most common cancer in women worldwide. This is caused by oncogenic types of human papillomavirus (HPV) infection. Although large numbers of young sexually active women get HPV-infected, only a small fraction develop cervical cancer. This points to different co-factors for regression of HPV infection or progression to cervical cancer. Host genetic factors play an important role in the outcome of such complex or multifactor diseases such as cervical cancer and are also known to regulate the rate of disease progression. The aim of this review is to compile the advances in the field of host genetics of cervical cancer. MEDLINE database was searched using the terms, 'HPV', 'cervical', 'CIN', 'polymorphism(s)', 'cervical'+ *the name of the gene* and 'HPV'+ *the name of the gene*. This review focuses on the major host genes reported to affect the progression to cervical cancer in HPV infected individuals.Indian Journal of Human Genetics 09/2011; 17(3):132-44.
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ABSTRACT: The functional outcome after stroke is unpredictable; it is not accurately predicted by clinical pictures upon hospital admission. The presence of apoptotic neurons in the ischemic penumbra and perihematoma area may account for poor prognosis, but whether the highly variable stroke outcome reflects differences in genetic susceptibility to apoptosis is elusive. The p53 tumor suppressor protein, an important transcriptional regulator of apoptosis, naturally occurs in humans in two variants with single nucleotide polymorphisms resulting in Arg or Pro at residue 72. We show that poor functional outcome after either ischemic or hemorrhagic stroke was linked to the Arg/Arg genotype. This genotype was also associated with early neurological deterioration in ischemic stroke and with increased residual cavity volume in intracerebral hemorrhage. In primary cultured neurons, Arg(72)-p53, but not Pro(72)-p53, interacted directly with mitochondrial Bcl-xL and activated the intrinsic apoptotic pathway, increasing vulnerability to ischemia-induced apoptotic cell death. These results suggest that the Tp53 Arg/Arg genotype governs neuronal vulnerability to apoptosis and can be considered as a genetic marker predicting poor functional outcome after stroke.Journal of Experimental Medicine 02/2011; 208(3):429-37. · 13.85 Impact Factor
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ABSTRACT: BACKGROUND: The p21 codon 31 single nucleotide polymorphism (SNP), rs1801270, has been linked to cervical cancer but with controversial results. The aims of this study were to investigate the role of p21 SNP-rs1801270 and other untested p21 SNPs in the risk of cervical cancer in a Chinese population. METHODS: We genotyped five p21 SNPs (rs762623, rs2395655, rs1801270, rs3176352, and rs1059234) using peripheral blood DNA from 393 cervical cancer patients and 434 controls. RESULTS: The frequency of the rs1801270 A allele in patients (0.421) was significantly lower than that in controls (0.494, p = 0.003). The frequency of the rs3176352 C allele in cases (0.319) was significantly lower than that in controls (0.417, p < 0.001).The allele frequency of other three p21 SNPs showed not statistically significantly different between patients and controls. The rs1801270 AA genotype was associated with a decreased risk for the development of cervical cancer (OR = 0.583, 95%CI: 0.399 - 0.853, P = 0.005). We observed that the three p21 SNPs (rs1801270, rs3176352, and rs1059234) was in linkage disequilibrium (LD) and thus haplotype analysis was performed. The AGT haplotype (which includes the rs1801270A allele) was the most frequent haplotype among all subjects, and both homozygosity and heterozygosity for the AGT haplotype provided a protective effect from development of cervical cancer. CONCLUSIONS: We show an association between the p21 SNP rs1801270A allele and a decreased risk for cervical cancer in a population of Chinese women. The AGT haplotype formed by three p21 SNPs in LD (rs1801270, rs3176352 and rs1059234) also provided a protective effect in development of cervical cancer in this population.BMC Cancer 12/2012; 12(1):589. · 3.01 Impact Factor