Association of p53 codon 248 (exon7) with urinary bladder cancer risk in the North Indian population (original) (raw)
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Role of p53 gene polymorphism and bladder cancer predisposition in northern India
Cancer biomarkers : section A of Disease markers
p53 is a major orchestrator of cellular response to a broad array of stress types by regulating apoptosis, cell cycle arrest, etc. A few polymorphic sites, one at codon72 of exon4, intron3 16bpdel/ins, intron6G>A have been studied with regard to Bladder cancer (BC) risk in North Indians. Genotypes were assessed in hospital-based case-control study comprising of 200BC cases, 265healthy controls. After extraction of genomic DNA from blood, genotyping was done using PCR Restriction Fragment Length Polymorphism. Individuals with p53R72P G>C, CC genotype demonstrated marginally reduced risk of BC (p=0.053, OR=0.29, 95% 16bp-ins/del.
TP53 is considered to be the most frequently mutated gene in every forms of human cancer. The objective of this study was to evaluate the association of TP53 codon 72 and 248 polymorphisms with the susceptibility and severity of bladder cancer in Bangladeshi population. A case-control study on 102 bladder cancer patients and 140 control subjects was conducted. The genotype analysis was done by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. The patients with Pro/Pro genotypes at 72 position were at high risk (odds ratio (OR)=3.02; 95 % confidence interval (95 % CI)=1.42 to 6.40) of developing bladder cancer. The cigarette smokers with Pro/Pro genotypes at 72 position were found to have a 3.91-fold increased risk to develop bladder cancer (OR=3.91; 95 % CI=1.33 to 11.5). There was no significant association of codon 248 polymorphisms with bladder cancer in the study population. Taken together, these findings indicate an association between p53 codon72 polymorphismand bladder cancer risk in Bangladeshi population.
Research Square (Research Square), 2019
Background Breast cancer (BC) is known to be the most common malignancy in females whereas colorectal cancer (CRC) incidence also higher in both genders in Sri Lanka. TP53 is an important tumour suppressor gene and its somatic mutations are reported in approximately 27% of BC and 43% of CRC cases. Analysis of TP53 gene variants not only provides clues for the aetiology of the tumour formation, but also has an impact on treatment efficacy. The current study was conducted to investigate the pattern of TP53 variants in patients with BC and CRC from Sri Lanka. Methods 30 patients with BC, 21 patients with CRC and an equal number of healthy controls were screened for mutational status of TP53 by polymerase chain reaction (PCR) followed by direct sequencing. In addition, a subset of these samples were analysed for the protein expression of p53 and comparison made with the mutational status of TP53. We also analysed the protein expression of p21 and MDM2 as potential indicators of p53 functional status and compared it with the protein expression of p53. Additionally, hotspot codons of the KRAS, BRAF and PIK3CA genes were also analysed in a subset of CRC patients. Results Twenty seven sequence variants, including several novel variants in the TP53 gene were found. Nine BC and seven CRC tumour samples carried pathogenic TP53 variants. Pathogenic point missense variants were associated with strong and diffuse positive staining for p53 by immunohistochemistry (IHC), whereas, wild type TP53 showed complete absence of positive IHC staining or rare positive cells, regardless of the type of cancer. There was no direct correlation between p21 or MDM2 expression and p53 expression in either BCs or CRCs. Four of the CRC patients had pathogenic hotspot variants in KRAS; three of them were on codon 12 and one was on codon 61. Conclusion The prevalence of pathogenic somatic TP53 variants was 31% and 33.33% in the studied BC and CRC cohorts respectively. All of them were located in exons 5-8 and the pathogenic missense variants were associated with strong immuno-positive staining for p53. In addition, association of BCs with CRCs is controversial, as some studies have suggested that BC survivors are at a higher risk of developing CRC due to risk factors such as obesity and the level of exogenous and endogenous sex hormones [11, 12] while other studies have proposed that there are no such associations [13]. In this study, we compared the mutation spectrum of TP53 among BCs and CRCs to evaluate their genetic basis. Furthermore, immunohistochemistry (IHC) was carried out to measure the protein expression of p53 and to correlate the immuno-detection of p53 with the mutational status of TP53 gene. We also studied the expression of p53 downstream targets and compared those with the immune-detection of p53. Methods Recruitment of the participants for the study and processing of the samples Ethical clearance (EC/14/160) was granted by the Ethics Review Committee of the Faculty of Medicine, University of Colombo, Sri Lanka. A total of 91 participants were recruited, which includes 30 patients with BC, 21 patients with CRC and 41 healthy controls (30 females, 11 males) without any personal or family history of cancer. Prior to the recruitment, the study was explained and written informed consent was obtained from the patients and healthy controls. Clinical and socio-demographic data of the participants were collected via medical reports and questionnaires respectively. One part of the surgically excised tumor tissues was placed in 10% formalin to make Formalin Fixed Paraffin Embedded (FFPE) blocks, while the other part was placed immediately in Allprotect ® Tissue Reagent (QIAGEN, cat no. 76405, Hilden, Germany) and stored at-20 0 C until processed. Genomic DNA extraction from the excised tumour piece of patients and from blood of healthy controls This study was funded by National Research Council, Sri Lanka (grant number 15-33) and Commonwealth Scholarship Commission of the UK (grant number LKCN-2015-100). These funding bodies had no role in the design of the study, collection, analysis, and interpretation of data and in writing the manuscript.
Urological Research, 2001
We studied the eect of the p53 gene Arg72Pro polymorphism on bladder cancer susceptibility in a case control study of 121 bladder cancer patients and 114 age-sex matched controls to determine whether this polymorphism is a biomarker for the risk and how aggressive the disease is. Genomic DNA was obtained from venous blood samples for genotype determination by PCR and restriction digestion. The genotype frequencies in the patient group were Arg/Arg: 0.3553, Arg/Pro: 0.4711, Pro/Pro: 0.1736, and in the control group Arg/Arg: 0.3684, Arg/Pro: 0.4825, Pro/Pro: 0.1491. The distribution of genotypes between the two groups was not statistically dierent (v 2 =0.260, df: 2, P=0.878). The patient group was subdivided into two groups as super®cial bladder cancer (n=88) and invasive bladder cancer (n=33), according to the presence of muscle invasion. The distribution of genotypes in the super®cial group was Arg/Arg: 0.3409, Arg/Pro: 0.5114, Pro/Pro: 0.1477 and in the invasive group Arg/Arg: 0.3940, Arg/Pro: 0.3636, Pro/Pro: 0.2424. No association was observed with the invasiveness of the tumor (v 2 =2.542, df: 2, P=0.281). Strati®cation of the data by tobacco exposure did not result in a signi®cant dierence in genotype frequencies. These data do not support an association between the p53 Arg72Pro polymorphism and bladder cancer.
Background: The high incidence and relatively good prognosis of breast cancer has made it the most prevalent cancer in the world today. A large number of distinct mutations and polymorphisms in the p53 gene have been reported worldwide, but there is no report regarding the role of this inherited susceptibility gene in breast cancer risk among the Bengalee Hindu Caste females of West Bengal, India. Aim of the Study: We investigated the distribution and the nature of p53 gene mutations and polymorphisms in exons 5-7 in a cohort of 110 Bengalee Hindu breast cancer patients and 127 age, sex and caste matched controls by direct sequencing. Results: We did not observe any mutations and polymorphisms in our studied individuals. Conclusion: We therefore conclude that mutations in exons 5-7 of p53 gene are rare causes of breast cancer among Bengalee Hindu caste females, and therefore of little help for genetic counseling and diagnostic purposes.
TP53 - Molecular soldier's mutations in bladder cancer in the Kashmiri population
Asian Pacific journal of cancer prevention: APJCP
Purpose: We made a preliminary attempt to study mutations in exons 5-8 (the DNA binding domain) of the tumor suppressor gene TP53, in urinary bladder cancer patients from Kashmir. Further the relation of clinicopathological characteristics with mutation status was asessed. Materials and Methods: The study population consisted of 60 patients diagnosed with transitional cell carcinomas who underwent transurethral resection and /or radical cystectomy. Mutations in 5-8 exons of TP53 gene were detected by means of single strand conformation polymorphism (SSCP). All samples which showed different migration bands in SSCP were confirmed by DNA sequencing. Results: 19 of 60 (31.6%) bladder cancers had mutations of the TP53 gene (11 transitions and 8 transversions), three were G→A transitions, two G→T transversions, three A→C transversions, five C→T transitions and six A→T transversions. Predominantly missense mutations (66%) were detected but no deletions or insertions were found. Statistically significant associations (<0.05) were noted with higher tumor stage (T2 or higher), recurrence and large tumor size (>3cm). No correlation was found between smoking and tumor grade and the presence of TP53 mutations. Conclusions: Mutation of the TP53 gene is one of the commonest genetic changes in human bladder cancer, also in a high risk ethnic Kashmiri population.