Role of Functional Polymorphisms of P53 and P73 Genes with the Risk of Prostate Cancer in a Case-Control Study from Northern India

Mittal, Rama Devi; George, Ginu P.; Mishra, Jyotsna; Mittal, Tulika; Kapoor, Rakesh

doi:10.1016/j.arcmed.2011.03.001

Cited by 29 publications

(28 citation statements)

References 26 publications

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“…In agreement with the results of the present study, Mittal et al (47) The intron sequences in TP53 are involved in regulating gene expression and in DNA-protein interactions (56,57). It has been proposed that the TP53 intron 3 16-bp I variant is associated with lower levels of TP53 transcripts, which suggests that this duplication polymorphism causes an alteration in mRNA processing and may be a risk factor for developing cancer (57).…”

Section: Patient Characteristicssupporting

confidence: 81%

Association between polymorphisms in TP53 and MDM2 genes and susceptibility to prostate cancer

et al. 2017

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Abstract. Tumor protein 53 (TP53), a tumor suppressor gene, is a vital cellular cancer suppressor in multicellular organisms. Murine double minute-2 (MDM2) is an oncoprotein that inhibits TP53 activity. A number of studies have examined the association of TP53 and MDM2 polymorphisms with the risk of common forms of cancer, but the findings remain inconclusive. The present study aimed to evaluate the impact of the 40-bp insertion/deletion (I/D) polymorphism (rs3730485) in the MDM2 promoter region and the 16-bp I/D polymorphism (rs17878362) in TP53 on the susceptibility of prostate cancer (PCa) in a sample of the Iranian population. This case-control study included 103 patients with pathologically confirmed PCa and 142 patients with benign prostatic hyperplasia. The IntroductionProstate cancer (PCa) is the most prevalent form of cancer among males in the United States (1). In Iran, the incidence of PCa is ~9.6 cases per 100,000 individuals, with a range of 3.2-16.0 per 100,000 in various geographical settings (2,3). This is comparable with the Asia-Pacific region (9.9 per 100,000), but significantly lower than in the rest of the world (32.8 per 100,000) (4). The median age at diagnosis is ~66 years and the 5-year survival rate of patients with PCa has been estimated to be 98.9% (5).The molecular mechanisms underlying the progression and carcinogenesis of PCa have not yet been clarified. Additional molecular markers that may be employed to detect PCa and to individualize patient therapy and prognosis are of great clinical importance. A number of large cohort and case-control studies with various populations suggest that family history is a primary risk factor for PCa (6-10).In humans, the tumor protein 53 (TP53) gene is located on the short arm of chromosome 17 (17p13.1) (11). TP53, an important tumor suppressor gene, is a crucial regulator of apoptosis and the cell cycle (12-15). When it is mutated, this regulation may be lost, leading to uncontrolled cell proliferation and potentially tumorigenesis (16).The human MDM2 gene is mapped on chromosome 12q14. 3-15 (17). MDM2 functions as a key negative regulator of TP53 (18)

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Section: Patient Characteristicssupporting

confidence: 81%

Association between polymorphisms in TP53 and MDM2 genes and susceptibility to prostate cancer

et al. 2017

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“…An allele frequency of Arg72Pro polymorphism has been reported to vary with respect to ethnicity and latitude (Nagpal et al, 2002). The allele frequency of proline at codon 72 varies from 0.12-0.69 worldwide (Francisco et al, 2011) whereas for the Indian population; it ranges from 0.42-0.72 (Nagpal et al, 2002;Tandle et al, 2001;Mitra et al, 2003;Mittal et al, 2011;Suresh et al, 2011). In our population, the frequency of proline was 0.46.…”

Section: Discussionmentioning

confidence: 99%

“…Meta-analysis by Zhuo et al (2009) on this polymorphism revealed that there was no association between Arg72Pro polymorphism and oral cancer risk. When comparison was made for all other cancers from India, proline allele was at risk for colorectal cancer and bladder cancer but it was found to be protective in breast cancer and prostate cancer and no association was observed for head and neck cancer (Pandith et al, 2010;Sameer et al, 2010;Suresh et al, 2010;Mittal et al, 2011). Studies from other populations showed conflicting results for the association of Arg72Pro polymorphism with oral cancer risk (Kietthubthew et al, 2003;Kuroda et al, 2007;Saini et al, 2011).…”

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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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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“…By contrast, another study of a Caucasian population performed by Quiñones et al (21) identified a positive association of the Pro/Pro genotype with prostate cancer risk (OR=2.89; 95% CI, 1.17-7.10). Studies carried out in Japan (22), China (23) and Northern India (24) reported the same increased association of the Pro allele with prostate cancer risk as the study by Quiñones et al (21), however, the studies of men in Argentina (27) and Iran (28) did not. One study by Ricks-Santi et al (26) found a significant association of the Arg allele with the prevalence of prostate cancer in populations of men of African descent.…”

Section: P21 C98a P21 C70t ------------------------------------------mentioning

confidence: 57%

“…The two variants were considered wild-type, resulting in a non-conservative change (6,15). In certain studies the Pro allele was associated with increased prostate cancer risk (21)(22)(23)(24)(25), while in others the Arg allele was associated with prostate cancer predisposition (26). Other studies, mainly larger studies and meta-analyses, did not detect any association of the p53 codon 72 polymorphism with prostate cancer risk (27)(28)(29)(30).…”

Section: Introductionmentioning

confidence: 99%

Association of p53 and p21 polymorphisms with prostate cancer

Sivoňová¹,

Vilčková²,

Kliment³

et al. 2015

Biomedical Reports

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Abstract. Cell cycle deregulation is common in human cancer. Alterations of the tumor-suppressor gene p53 and its downstream effector p21 have been indicated in the development of numerous human malignancies. Therefore, we hypothesize that the p53 codon 72 polymorphism, either on its own or in combination with p21 (C98A and C70T) polymorphisms, modifies the risk of prostate cancer within the Slovak population, and no previous studies have investigated these gene-gene interactions in the pathogenesis of prostate cancer in the Slovak population. Polymerase chain reaction-restriction fragment length polymorphism was used to determine the p53 and p21 genotypes in subjects comprising 300 prostate cancer patients and 446 healthy individuals. These 3 polymorphisms individually did not correlate with the prostate cancer risk. Conversely, the interaction between the p53 and p21 polymorphisms significantly decreased the risk of prostate cancer, with the odds ratio (OR) being 0.49 [95% confidence interval (CI), 0.27-0.86; P<0.05] for subjects carrying the p53 codon 72 arginine (Arg)/proline (Pro)+Pro/Pro and p21 C98A CA genotypes compared to the combined reference genotypes p53 codon 72 Arg/Arg and p21 C98A CC. Neither the p53 genotypes nor the p21 genotypes showed statistically significant differences in Gleason score or serum prostate-specific antigen levels (P>0.05). A decreased risk of prostate cancer association with the p21 C98A CA genotype (OR=0.58; 95% CI, 0.36-0.93; P<0.05) in non-smokers compared to the non-smokers with the p21 C98A CC genotype was observed. Smokers carrying the p53 codon 72 Pro/Pro genotype were not at any significant risk of prostate cancer (OR=2.97; 95% CI, 0.51-17.15) compared to the non-smokers with the Arg/Arg genotype. Taken together, to the best of our knowledge this is the first study to show that a combination of the variant genotypes of p53 codon 72 and p21 C98A may modify the prostate cancer risk within the Slovak population.

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Role of Functional Polymorphisms of P53 and P73 Genes with the Risk of Prostate Cancer in a Case-Control Study from Northern India

Cited by 29 publications

References 26 publications

Association between polymorphisms in TP53 and MDM2 genes and susceptibility to prostate cancer

Association between polymorphisms in TP53 and MDM2 genes and susceptibility to prostate cancer

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

Association of p53 and p21 polymorphisms with prostate cancer

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