Identification of Genetic Variants in Exon 4 of TP53 in Lung Carcinoma and in Silico Prediction of Their Significance.

Lung cancer is a severe and the leading cause of cancer related deaths in men and women all over the world. Tumor suppressor protein (TP53) encoded by the TP53 gene which plays a pivotal role in various cellular tumor suppression processes viz cell cycle arrest and apoptosis. Henceforth, the present study was aimed to TP53 exon4 variants from lung carcinoma. Histopathologic and clinically proven 20 patients of lung cancer were enrolled in this study the average age of patients was 45 ± 8 years which categorized as early onset of lung cancer. Genomic DNA was isolated from the blood specimen of patients. Extracted DNA was subjected to PCR amplification for exon 4 of TP53 using appropriate primers and subsequently amplified products were applied to nucleotide alterations via using the DNA sanger sequencing. The genetic analysis documented five variants in exon4 of TP53 which include viz. 4 substitutions [c.215 > C at codon 72, C. 358-359AA > GG at codon 120] were highly prevalent, occurring in 63% and 25% frequency in patients. Other two variants viz. C. 358 A > C at codon 120, C. 365T > G at codon 122 were present at frequency of 15% whilst one deletion variant [152 del C] was found with 5% frequency. Furthermore, alterations on codon 72, 120,122 and 51 were characterized as possibly damaging by Poly Phen-2 and decreased stability using stability bioinformatic tool. Taken together all these findings infer that TP53 gene involved in modulation and susceptibility to lung cancer.

Association of TP53 Single Nucleotide Polymorphisms with Prostate Cancer in a Racially Diverse Cohort of Men.

Growing evidence indicates the involvement of a genetic component in prostate cancer (CaP) susceptibility and clinical severity. Studies have reported the role of germline mutations and single nucleotide polymorphisms (SNPs) of TP53 as possible risk factors for cancer development. In this single institutional retrospective study, we identified common SNPs in the TP53 gene in AA and CA men and performed association analyses for functional TP53 SNPs with the clinico-pathological features of CaP. The SNP genotyping analysis of the final cohort of 308 men (212 AA; 95 CA) identified 74 SNPs in the TP53 region, with a minor allele frequency (MAF) of at least 1%. Two SNPs were non-synonymous in the exonic region of TP53: rs1800371 (Pro47Ser) and rs1042522 (Arg72Pro). The Pro47Ser variant had an MAF of 0.01 in AA but was not detected in CA. Arg72Pro was the most common SNP, with an MAF of 0.50 (0.41 in AA; 0.68 in CA). Arg72Pro was associated with a shorter time to biochemical recurrence (BCR) (p = 0.046; HR = 1.52). The study demonstrated ancestral differences in the allele frequencies of the TP53 Arg72Pro and Pro47Ser SNPs, providing a valuable framework for evaluating CaP disparities among AA and CA men.

Associations of MDM2 rs2279744 and TP53 rs1042522 polymorphisms with cervical cancer risk: A meta-analysis and systematic review.

Background: Although the association between MDM2 rs2279744 and TP53 rs1042522 polymorphisms and cervical cancer has been reported, the results of its correlation were contradictory. Thus, we conducted a meta-analysis to precisely verify the relationships between MDM2 rs2279744 and TP53 rs1042522 polymorphisms and cervical cancer. Methods: We thoroughly searched the PubMed, Web of Science, Embase, and Scopus databases for all potential articles from inception to June 2022 and used R Version 4.1.2 and STATA software 12.0 for the meta-analysis. The odds ratios (ORs), 95% confidence intervals (CIs) and 95% prediction intervals (PIs) were calculated to evaluate the associations. Subgroup analyses stratified by ethnicity, source of control, quality score and adjustment were further conducted to assess the relationship between MDM2 rs2279744 and TP53 rs1042522 polymorphisms and cervical cancer. Results: A total of 30 case-control studies involving 5025 cases and 6680 controls were included. All the included studies were population-based or hospital-based studies. The overall analysis showed that MDM2 rs2279744 polymorphism was closely related to an increased risk of cervical cancer in the recessive model (GG vs GT + TT: OR = 1.602, 95% CI: 1.077-2.383, P = 0.020) and homozygote model (GG vs TT: OR = 1.469, 95% CI: 1.031-2.095, P = 0.033, 95% PI: 0.516-4.184). A significant correlation between TP53 rs1042522 polymorphism and cervical cancer was observed in two models (CC + CG vs GG: OR = 1.759, 95% CI: 1.192-2.596, P = 0.004, 95% PI: 0.474-6.533; GG vs CC: OR = 2.442, 95% CI: 1.433-4.162, P = 0.001, 95% PI: 0.456-13.071). Conclusions: This meta-analysis revealed that MDM2 SNP309T>G and TP53 rs1042522 C>G polymorphisms were associated with the increased risk of cervical cancer.

p53 Arg72Pro polymorphism, adiposity status, and cancer risk: Two case-cohorts within a Japanese prospective study.

The tumor suppressor protein, p53, is a critical molecule involved in cancer development. However, the association between p53 Arg72Pro polymorphism and cancer risk remains unclear, possibly due to the pro-tumor potential of p53 under metabolic stress. Here, we hypothesized that the p53 Arg72Pro polymorphism plays different roles during tumorigenesis by adiposity status. We measured baseline body mass index (BMI) and p53 Arg72Pro polymorphism for two case-cohorts, which included 4264 cancers with up to 20 years of follow-up. Multivariable-adjusted hazard ratios (HRs) and confidence intervals (CIs) were estimated using weighted Cox proportional-hazards method. Without consideration of adiposity status, p53 Arg72Pro polymorphism was not associated with cancer risk. However, proline (Pro) homozygous genotype conferred an increased cancer risk for individuals with a BMI <25 kg/m2 (HR [95% CI]: 1.12 [1.00-1.26] for total cancer and 1.19 [1.02-1.38] for obesity-related cancer), but not for those with a BMI ≥ 25 kg/m2 . The heterogeneous effect of p53 Arg72Pro polymorphism on cancer risk according to adiposity status was indicated (pheterogeneity : 0.07 for total cancer and 0.03 for obesity-related cancer). Furthermore, the association between overweight and cancer risk was only observed in arginine (Arg) carriers, but not in Pro homozygous carriers (pheterogeneity : 0.07 for total cancer and 0.02 for obesity-related cancer). Pro homozygous carriers were more likely to be predisposed to cancer than Arg carriers with normal-weight conditions. In addition, overweight was related to a higher cancer risk in Arg carriers than Pro homozygous carriers. Our findings may suggest the adiposity-dependent dual effects of p53 Arg72Pro polymorphism during tumorigenesis.

Association between TP53 Arg72Pro variant and recurrent pregnancy loss in the Greek population.

OBJECTIVES: The present case-control study investigates whether TP53 Arg72Pro variant (rs1042522) serves as a risk factor for recurrent pregnancy loss (RPL) in Greek women. METHODS: The study group consisted of 100 patients with at least two miscarriages of unexplained etiology, before the 24th week of gestation. The control group included 106 women with no pregnancy loss history. DNA was extracted and genotyped using specific primers for PCR amplification of the Arg72 and Pro72 alleles. Sanger sequencing was used for the discrimination between heterozygotes and homozygotes for Arg72Pro variant. RESULTS: This is the first study demonstrating the statistically significant higher frequency of TP53 Arg72Pro variant in Greek RPL women compared to controls (38% vs. 6.6%; OR=8.6682, 95% CI: 3.6446-20.6160; p<0.0001). GC genotype (Arg/Pro) and CC genotype (Pro/Pro) were statistically more common in RPL patients than in controls (16% vs. 1.9%; p=0.0027, and 22 vs. 4.7%; p=0.0008, respectively). C allele frequency was statistically significant higher in RPL group than in controls (30.0 vs. 5.7%; p<0.0001). According to the inheritance mode analysis, the model that best fit the data was the dominant model (OR=8.67, 95% CI=3.64-20.62; p<0.0001). CONCLUSIONS: The is the first study disclosing strong evidence that TP53 rs1042522 is significantly associated with a higher risk for recurrent pregnancy loss in Greek women following a dominant model, thus, serving as a genetic marker for identifying women at increased risk of recurrent miscarriages.

Association Analysis of TP53 rs1042522, MDM2 rs2279744, rs3730485, MDM4 rs4245739 Variants and Acute Myeloid Leukemia Susceptibility, Risk Stratification Scores, and Clinical Features: An Exploratory Study.

This study aimed to explore the associations between the TP53 rs1042522 (TP53 Arg72Pro), MDM2 rs2279744 (MDM2 309T>G), rs3730485 (MDM2 del1518), MDM4 rs4245739 (MDM4 34091 C>A) variants and odds of developing acute myeloid leukemia (AML) in a cohort of 809 adult subjects, consisting of 406 healthy controls and 403 AML patients. Model-based multifactor dimensionality reduction (MB-MDR) framework was used to identify the interactions of the mentioned variants and their association with AML risk. Associations of the mentioned variants with clinical features of AML, somatic mutations, and response to treatment were also evaluated. Significant associations between TP53 rs1042522 and MDM4 rs4245739 variants and AML susceptibility were noticed. MB-MDR and logistic regression analysis revealed an interaction between MDM2 rs2279744 and TP53 rs1042522, between MDM4 rs4245739 and MDM2 rs3730485, as well as significant associations with AML susceptibility. Several associations between the mentioned variants and clinical features of AML and somatic mutations were also noticed. Individually, the variant genotypes of TP53 rs1042522 and MDM4 rs4245739 were associated with AML susceptibility, but their interaction with MDM2 rs2279744 and rs3730485 modulated the risk for AML. The variant genotypes of TP53 rs1042522 were associated with adverse molecular and cytogenetic risk and also with NPM1 mutations.

Association of TP53 Codon 72 Arg>Pro Polymorphism with Breast and Lung Cancer Risk in the South Asian Population: A Meta-Analysis.

BACKGROUND: A transversion missense polymorphism of the TP53 tumor suppressor gene at the codon 72 codes proline instead of arginine causes an altered p53 protein expression and has been found to be associated with an elevated risk of various cancer; especially breast and lung cancer. As the previous case-control studies on the South Asian population have shown controversial results, we performed a meta-analysis to evaluate a precise estimation of the relationship between the TP53 Arg72Pro polymorphism with breast and lung cancer. METHODS: A total of 12 related studies on the South Asian population have been included through comprehensive database searching. Six studies were selected for breast cancer meta-analysis involving 950 cases and 882 controls; the other six studies were for lung cancer meta-analysis including 975 cases and 1397 controls. The results have been determined by using the Review Manager (RevMan) 5.3. Additionally, the stability of our analysis was assessed by heterogeneity, publication bias analysis and sensitivity testing. RESULTS: A significantly increased risk of breast cancer was found in Pro allele (Pro vs. Arg), co-dominant model 2 (Pro/Pro vs. Arg/Arg), dominant model (Pro/Pro + Arg/Pro vs. Arg/Arg). In case of lung cancer, significantly increased risk was found in the allele, co-dominant 1, co-dominant 2, co-dominant 3, dominant, and recessive models. No association with other genetic models with breast and lung cancer risk was found in the South Asian population. CONCLUSIONS: Our results indicate that TP53 Arg72Pro polymorphism is a risk factor for the development of breast cancer and lung cancer in the South Asian population.

TP53 Arg72Pro polymorphism and neuroblastoma susceptibility in eastern Chinese children: a three-center case-control study.

TP53 is a tumor suppressor gene that regulates cell growth, apoptosis and DNA repair. Previous studies have reported the contribution of TP53 Arg72Pro (rs1042522 C>G) polymorphism to pathogenesis of multiple tumors. Hence, we evaluated the association between this polymorphism and neuroblastoma susceptibility in eastern Chinese children. The Taqman genotyping assay was performed in 373 patients and 762 controls. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association. No significant association was found between the TP53 gene rs1042522 C>G polymorphism and neuroblastoma susceptibility in the overall analysis (CG vs. CC: adjusted OR = 0.92, 95% CI = 0.70-1.22, P=0.567; GG vs. CC: adjusted OR = 0.99, 95% CI = 0.69-1.42, P=0.947; CG/GG vs. CC: adjusted OR = 0.94, 95% CI = 0.72-1.23, P=0.639; or GG vs. CC/CG: adjusted OR = 1.04, 95% CI = 0.75-1.43, P=0.814) and stratified analysis by age, gender, sites of origin, and clinical stages. The TP53 gene rs1042522 C>G polymorphism may not be a risk factor for neuroblastoma in eastern Chinese children. Future studies are needed to confirm this negative result and to reveal additional functional TP53 variants predisposing to neuroblastoma.

ТР53 Codon 72 Polymorphism and Human Papilloma Virus-Associated Cervical Cancer in Kyrgyz Women

Background: The aim of this study was to ascertain the magnitude of association of gene ТР53 Arg72Pro polymorphic marker with cervical cancer (CC) in Kyrgyz women. Methods: We identified and included 205 women of Kyrgyz ethnicity for this case-control study, of whom N=103 were women (mean age 53.5 ± 10.0 years) with histologically confirmed CC and N=102 controls (mean age 46.5 ± 8.5 years). We detected human papilloma virus (HPV) DNA types 16 and 18 using polymerase chain reaction (PCR) with hybridization/fluorescent detection. Genotypes of ТР53 gene Arg72Pro polymorphism were identified using PCR-RFLP assay. Results: Eighty-eight percent (90/103) women with CC had HPV, of whom 43.4% (39/90) had HPV type 16, 24.4% (22/90) had HPV type 18, whereas 32.2% (29/90) carried both types. The univariate analysis of allele and genotype distribution of Arg72Pro polymorphic marker of ТР53 gene showed no difference between CC and control groups (χ2=1.24, р=0.54). However, when CC cases associated with HPV were tested against controls, Arg72 allele and Arg72Arg genotype prevalence were greater compared to controls (χ²=7.25; р=0.027 for genotypes and χ²=6.83; р=0.009 for alleles). In HPV-positive women, Arg72Arg genotype of ТР53 gene was associated with a 1.85-fold increase in the likelihood of CC (OR=1.85 [95% confidence interval (CI) 1.03-3.32]), whereas Arg72 allele increased this likelihood 1.94-fold (OR=1.94 [95% CI 1.20-3.15]). Conclusions: Arg72Arg genotype and Arg72 allele of ТР53 gene in Kyrgyz women increase the risk of HPV-associated CC.

The Neuronal Ischemic Tolerance Is Conditioned by the Tp53 Arg72Pro Polymorphism.

Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of pro-survival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulator MDM2. Moreover, we have previously described that the human Tp53 Arg72Pro single nucleotide polymorphism (SNP) controls susceptibility to ischemia-induced neuronal apoptosis and governs the functional outcome of patients after stroke. Here, we studied the contribution of the human Tp53 Arg72Pro SNP on PC-induced neuroprotection after ischemia. Our results showed that cortical neurons expressing the Pro72-p53 variant exhibited higher PC-mediated neuroprotection as compared with Arg72-p53 neurons. PC prevented ischemia-induced nuclear and cytosolic p53 stabilization in Pro72-p53 neurons. However, PC failed to prevent mitochondrial p53 stabilization, which occurs in Arg72-p53 neurons after ischemia. Furthermore, PC promoted neuroprotection against ischemia by controlling the p53/active caspase-3 pathway in Pro72-p53, but not in Arg72-p53 neurons. Finally, we found that good prognosis associated to TIA within 1 month prior to ischemic stroke was restricted to patients harboring the Pro72 allele. Our findings demonstrate that the Tp53 Arg72Pro SNP controls PC-promoted neuroprotection against a subsequent ischemic insult by modulating mitochondrial p53 stabilization and then modulates TIA-induced ischemic tolerance.

Meta-analysis for the association between TP53 Arg72Pro polymorphism and human thyroid cancer risk / 中华内分泌代谢杂志

Objective To explore the association of single nucleotide polymorphism ( SNP ) in TP53 Arg72Pro (rs1042522) locus with thyroid cancer risk in human. Methods Articles involved in the association between SNP in TP53 Arg72Pro ( rs1042522) locus and thyroid cancer risk were retrieved from PubMed, Embase, and Web of Science databases, and studies which met the inclusion criteria were included. The meta-analysis, sensitivity analysis, subgroup analysis, and the assessment of publication-bias were performed by Stata 14. 0 software. The odds ratio ( OR) and their corresponding 95％ Confidence Intervals ( CI) were used to determine the strength of association between SNP in TP53 Arg72Pro locus and thyroid cancer risk. Results Thirteen case-control studies were eligible for this meta-analysis, including 2112 thyroid cancer cases and 4000 control subjects. Overall, mutated homozygous genotype ( Pro/Pro) in TP53 Arg72Pro ( rs1042522) locus was associated with significantly increased thyroid cancer risk(Recessive model, OR=1.78, 95％CI 1.24-2.56, P=0.002), showing a significantly higher Pro mutation frequency among thyroid cancer patients ( Allelic model, OR=1. 35, 95％ CI 1. 12-1. 63, P=0.002). In the stratified analysis, mutated homozygous genotype (Pro/Pro) in TP53 Arg72Pro (rs1042522) locus was only asscociated with significantly increased thyroid cancer risk among Asians, but not among Europeans and South Americans;mutated homozygous genotype ( Pro/Pro) in TP53 Arg72Pro ( rs1042522) locus was asscociated with significantly increased risk of papillary thyroid carcinomas ( PTC) among total population, but not medullary thyroid carcinomas. Conclusion There is a significant association between TP53 Arg72Pro polymorphism in TP53 and thyroid cancer risk, and the mutated homozygous genotype ( Pro/Pro) in this locus of TP53 maybe a risk factor for thyroid carcinoma among Asians.

Association between p53 Arg72Pro polymorphism and colorectal cancer risk in Asian population: a meta-analysis.

Although several published studies have investigated the association between p53 Arg72Pro polymorphism and the risk of colorectal cancer (CRC), their results have been ambiguous. To examine the overall relationship between published case-control studies of Asian subjects, we conducted a meta-analysis based on 13 studies. Databases PubMed, EMBASE, Web of Knowledge, and the Chinese National Knowledge Infrastructure were screened for studies carried out up to November 1, 2017. To evaluating the association, crude odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated. The results of our meta-analysis indicated that the p53 Arg72Pro gene polymorphism does not correlate with the risk of CRC in the pooled analysis. However, significant results were found in Chinese population (allele model: OR = 1.26, 95% CI = 1.03-1.53; homozygous model: OR = 1.62, 95% CI = 1.09-2.40; recessive model: OR = 1.49, 95% CI = 1.22-1.82). Moreover, in subgroup analyses, the Pro/Pro genotype was significantly associated with rectal cancer, and not colon cancer. Stratification by source of control and gender indicated that Pro/Pro genotype and Pro allele also correlated with CRC risk in the population-based subgroup and in men. Thus, our current meta-analysis indicates no evidence for the association between the p53 Arg72Pro polymorphism and CRC risk in the Asian population, but significant association in Chinese population, especially for rectal cancer and in men. Further research with larger population sizes is still warranted to confirm this result.

Impact of p53 arg72pro SNP on Breast Cancer Risk in North Indian Population.

BACKGROUND: Genetic changes in p53 gene contribute to breast cancer susceptibility. OBJECTIVE AND METHODS: A case-control study and a meta-analysis were performed to investigate the role of p53 codon72 SNP with breast cancer susceptibility in Indian women. RESULTS: p53 heterozygous arginine variant was associated with decreased risk of breast cancer in total cohort. In meta-analysis, Allelic and GG vs. CC genetic comparison model were found to be associated with breast cancer risk. Moreover, recessive comparison model indicated a protective correlation with breast cancer occurrence. CONCLUSION: The findings of our case-control study and meta-analysis suggest a significant association between p53 Arg72Pro polymorphism and an increased risk of breast cancer in Indian population.

The 72Pro Variant of the Tumor Protein 53 Is Associated with an Increased Breast Cancer Risk in the Moroccan Population.

BACKGROUND: The purpose of our case control study is to explore the potential association of tumor protein 53 (TP53) c.215G>C, p. (Arg72Pro) polymorphism (rs1042522) with the risk of breast cancer (BC) development in the Moroccan population. METHODS AND RESULTS: The study population consisted of 125 female patients with confirmed BC and 126 healthy controls. DNA samples were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism assay method using BstUI restriction enzyme. We showed that the homozygous genotype of TP53 72Pro variant was significantly associated with increased BC risk (OR 2.2, 95% CI 1.07-4.54, p = 0.03). The dominant and additive models of TP53 Pro allele were also correlated to the risk of BC (OR 2.13, 95% CI 1.07-4.23, p = 0.02 and OR 1.49, 95% CI 1.03-2.16, p = 0.03, respectively). Furthermore, the TP53 Arg72 variant was associated with protection against BC, either in the homozygous genotype, the dominant or the additive models (OR 0.45, 95% CI 0.22-0.93, p = 0.03; OR 0.46, 95% CI 0.23-0.92, p = 0.029 and OR 0.67, 95% CI 0.46-0.97, p = 0.03, respectively). CONCLUSION: Our results suggest that TP53 c.215G>C, p. (Arg72Pro) polymorphism may be considered as a genetic marker for predisposition to BC in Moroccan population.

TP53 Arg72Pro polymorphism is associated with increased overall survival but not response to therapy in Portuguese/Caucasian patients with advanced cervical cancer.

Identification of mechanisms that influence the therapeutic response and survival in patients with cancer is important. It is known that the genetic variability of the host, including presence of genetic polymorphisms in genes involved in DNA damage response, serves a crucial role in the prognosis of these patients. The present hospital-based retrospective cohort study aimed to evaluate the influence of TP53 Arg72Pro (rs1042522) polymorphism in the clinical outcome of 260 Caucasian patients diagnosed with cervical cancer and treated with concomitant radiotherapy and chemotherapy. The polymorphism genotyping was assessed using allelic discrimination by quantiative polymerase chain reaction. The results indicate that the TP53 Arg72Pro polymorphism did not significantly impact the response to therapy (P=0.571) nor disease-free survival (P=0.081). However, the polymorphism did influence overall survival, as increased median survival time was observed for patients carrying Arg/Pro genotype when compared with patients with Arg/Arg and Pro/Pro genotypes (126 months vs. 111 months, respectively; P=0.047). To conclude, the present findings suggest that a pharmacogenomic profile based on the genetic background of patients, including the analysis of the TP53 genotypes, may individualize treatment nad assist in the selection of therapies that may improve clinical outcome and lower toxicity for the patients.

Tumor Protein p53 (TP53) Gene and Left Main Coronary Artery Disease.

Patients with left main (LM) coronary artery disease (CAD) are at the highest risk of cardiovascular events. We evaluated possible gene polymorphisms of tumor protein 53 ( TP53, rs1042522, p.Arg72Pro) that can differentiate LM-CAD from patients with more peripheral CAD (MP-CAD) and healthy participants (control group) in 520 individuals (LM-CAD, n = 175; MP-CAD, n = 185; and control group, n = 160). Patients with LM-CAD had the lowest Arg/Arg genotype frequency (36.0%) compared with the MP-CAD (57.3%) and control groups (61.9%), P < .001 for both comparisons. Similarly, the Arg allele was more frequent in the control group than in patients with MP-CAD (78.8% vs 73.2%; P = .007) and LM-CAD (78.8% vs 64.0%; P < .001). The Arg/Pro genotype was more frequent in the LM-CAD group compared with the MP-CAD and control groups (56.0, 31.9, and 33.8, respectively, P < .001 for both comparisons). Furthermore, the frequency of Arg/Arg genotypes was the lowest in the LM-CAD group compared with the MP-CAD and control groups. Knowing that TP53 is an antioncogene protein that acts as a tumor suppressor and regulator of apoptosis, the lowest frequency of Arg/Arg genotype observed in these high-risk patients may indicate lower protection from the atherosclerosis process. Replication studies are needed to evaluate this association.

Association of p53 Codon 72 Polymorphism with Breast Cancer in a Rwandese Population.

BACKGROUND AND AIMS: A common polymorphism in the tumor suppressor gene p53 at codon 72 has been suggested to play a role in the development of a number of cancers. This polymorphism has been studied in many populations worldwide, with conflicting results. The present study was planned to assess the association of p53 codon 72 polymorphism with breast cancer development in a Rwandese population. METHODS: In this study, the polymorphism was examined by allele-specific PCR analysis in 40 patients with breast cancer and 39 healthy controls. RESULTS: The heterozygous genotype Pro/Arg prevailed in both breast cancer patients and controls, and was present in 80% (32/40) and 92.3% (36/39) of cases, respectively. No statistically significant association was observed between p53 codon 72 polymorphism and breast cancer risk. Distribution of p53 genotypes was also studied according to familial history, tumor grade, and clinical stage, and results clearly showed no statistically significant difference. CONCLUSION: These results suggest that p53 codon 72 polymorphism could not be assessed as a risk factor marker for predisposition to breast cancer in Rwanda. However, further studies using larger sample sizes are needed to provide more conclusive results and to investigate other genetic mutations affecting the activity of p53.

TP53 Arg72 as a favorable prognostic factor for Chinese diffuse large B-cell lymphoma patients treated with CHOP.

BACKGROUND: TP53 Arg72Pro (SNP rs1042522) is associated with risk of non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of NHL. However, the relationship between this SNP and prognosis of DLBCL in Asians is unknown. METHODS: Genotyping of TP53 Arg72Pro was done in 425 Chinese DLBCL patients. Two hundred and eighty-nine patients were treated with R-CHOP, and 136 patients received CHOP or CHOP-like as frontline regimen. Three hundred and ninety-six patients were assessable for the efficacy. RESULTS: Patients with Arg/Arg and Arg/Pro at codon 72 of TP53 had a higher complete response rate (61% vs. 44%, P = 0.007) than those with Pro/Pro. In the subgroup treated with CHOP or CHOP-like therapy, patients with Arg/Arg and Arg/Pro showed a higher 5-year overall survival (OS) rate than those with Pro/Pro (68.8% vs. 23.2%, P = 0.001). Multivariate Cox regression analysis revealed TP53 Arg72 as a favorable prognostic factor in this group. However, the combination of rituximab with CHOP significantly increased the 5-year OS rate of patients with Pro/Pro to 63%. CONCLUSION: This study revealed TP53 Arg72 as a favorable prognostic factor for Chinese DLBCL patients treated with CHOP or CHOP-like as frontline therapy.

Effect of p53 Arg72Pro polymorphism on the induction of micronucleus by aflatoxin B1 in in vitro in human blood lymphocytes.

Aflatoxin B1 (AFB1) is a class 1 carcinogen produced by Aspergillus flavus and Aspergillus parasiticus that can contaminate a variety of food substances, the liver being its target organ. A common p53 Arg72Pro polymorphism resulting in the substitution of an arginine amino acid by proline amino acid in the transactivating domain has been demonstrated to affect p53 function. The aim of this study is to investigate association between p53 Arg72Pro polymorphism and the frequencies of spontaneous and AFB1-induced DNA damage in peripheral blood lymphocytes from 100 healthy individuals in Turkish population. In vitro cytokinesis-blocked micronucleus (CBMN) assay was used to detect the spontaneous and AFB1-induced DNA damage whereas, genotyping of p53 Arg72Pro polymorphism was carried out by using a polymerase chain reaction restriction fragment length polymorphism assay. During 68 h incubation time, lymphocytes treated with AFB1 (1.56 µg/mL) and S9 mix for a total of 3 h (48-51 h). Treatment of the lymphocytes with AFB1 significantly increased the overall frequencies of micronucleus (MN) when compared to untreated cultures (1.23 ± 0.05 versus 0.55 ± 0.02; p <0.001). Moreover, genotype analysis revealed a statistically significant association between Pro/Pro genotype of p53 Arg72Pro polymorphism and increased frequencies of MN both spontaneous and AFB1-induced cultures when compared Arg/Arg genotype (0.69 ± 0.19 versus 0.46 ± 0.13, p < 0.001; 1.59 ± 0.65 versus 1.01 ± 0.41 p < 0.001; respectively). Our data indicate that p53 Arg72Pro polymorphism plays a significant role in human sensitivity to the genotoxic effects of AFB1. Further investigations in larger sample size and with different ethnic origins as well as including more functional single nucleotide polymorphisms might lead to the identification of novel genetic factors responsible for susceptibility to human carcinogens such as AFB1.

p53 Arg72Pro polymorphism confers the susceptibility to endometriosis among Asian and Caucasian populations.

PURPOSE: Findings from studies on the association between the p53 Arg72Pro polymorphism and endometriosis susceptibility have so far been inconsistent. Therefore, we undertook a meta-analysis to clarify the association of p53 Arg72Pro polymorphism with the risk of endometriosis. METHODS: Relevant studies were chosen by searching PubMed, Embase, the Cochrane Library databases, CNKI, Wanfang database, and CBM for articles published before and up to April 30, 2015. Two independent reviewers performed the eligibility evaluation and data extraction. The odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for the overall risk estimate. RESULTS: Eleven case-control studies involving 1834 endometriosis cases and 2331 controls were included. Pooled data analysis suggested that the p53 72Pro variant is a significant endometriosis risk factors in comparison to the 72Arg variant (Pro vs. Arg: OR = 1.298, 95 % CI 1.082-1.558; Pro/Pro vs. Arg/Arg: OR = 1.751, 95 % CI 1.130-2.711; Pro/Arg vs. Arg/Arg: OR = 1.530, 95 % CI 1.174-1.994), which was strengthened in the dominant model (Pro/Pro + Arg/Pro vs. Arg/Arg: OR = 1.570, 95 % CI = 1.181-2.087). In the stratified analysis by ethnicity and Hardy-Weinberg equilibrium (HWE) in the controls, we found strong associations in Asians and in studies that were consistent with HWE. However, the analyses of the revised American Fertility Society (rAFS) stage and the menopausal status subgroup did not reveal any significant associations. CONCLUSION: In conclusion, the p53 Arg72Pro polymorphism was closely related to the risk of endometriosis, especially in Asian populations.