Associations of TP53 codon 72 polymorphism with complications and comorbidities in patients with type 1 diabetes.

Wild-type TP53 plays an important role in the regulation of immune response and systemic inflammation. In type 1 diabetes (T1D), TP53 pathways are upregulated and an increased susceptibility to apoptosis is observed. We hypothesize that TP53 codon 72 polymorphism could be associated with complications and comorbidities in patients with T1D. We have investigated the associations of the TP53 codon 72 polymorphism with the T1D complications and comorbidities (retinopathy, nephropathy, hypertension, dyslipidemia, autoimmune thyroiditis, and celiac disease) in 350 patients. The key results of our approach are as follows: (1) In diabetic subjects, the Pro/Pro genotype is associated with an increased risk of microvascular complications, dyslipidemia, and celiac disease; (2) the Arg/Arg variant is associated with a decreased risk of autoimmune thyroiditis and celiac disease; (3) the Pro allele is associated with an increased risk of dyslipidemia, autoimmune thyroiditis, and celiac disease. Although further studies are required, our results for the first time indicate that the TP53 codon 72 polymorphism could be considered a genetic marker to predict the increased susceptibility to some T1D complications and comorbidities. KEY MESSAGES: We analyzed the TP53 codon 72 polymorphism in patients with T1D. Pro/Pro genotype is associated with an increased risk of microvascular complications, dyslipidemia, and celiac disease. The Arg/Arg variant is associated with a decreased risk of autoimmune thyroiditis and celiac disease. The Pro allele is associated with an increased risk of dyslipidemia, autoimmune thyroiditis, and celiac disease.

Recurrence risk evaluation in T1N1M0/T2N0M0/T3N0M0 gastric cancer with TP53 codon 72 polymorphisms.

BACKGROUND: Postoperative adjuvant chemotherapy is not indicated for T1N1M0/T2N0M0/T3N0M0 gastric cancer. However, approximately 10% to 30% of these patients experience recurrence and metastasis. METHODS: Among 658 patients with gastric cancer who received gastrectomy with curative intent, 130 T1N1M0/T2N0M0 and 73 T3N0M0 patients were enrolled. Overall survival (OS) and relapse-free survival (RFS) were analyzed based on TP53 codon 72 polymorphisms Arg/Arg, Arg/Pro, and Pro/Pro. The hazard ratio (HR) for each subgroup was compared by TP53 codon 72 polymorphisms. RESULTS: Of the 189 patients for whom polymorphism analysis results were available, the 5- and 10-year OS was 84.9% and 65.1%, respectively. The 5- and 10-year RFS was 81.8% and 65.4%, respectively. When the study cohort was divided into two groups according to polymorphism status (ie, "Arg/Arg and Arg/Pro" vs Pro/Pro), both the OS (HR, 2.799; 95% confidence interval [CI], 1.071-7.315; P = .036) and RFS (HR, 2.639; 95% CI, 1.025-6.794; P = .044) of the Pro/Pro group were significantly lower than those for the Arg/Arg and Arg/Pro groups across the entire observation period. CONCLUSIONS: The TP53 codon 72 Pro/Pro polymorphism may isolate a relatively high-risk patient group in T1N1M0/T2N0M0/T3N0M0 gastric cancer.

Association of TP53 gene codon 72 polymorphism with Helicobacter pylori-positive non-cardia gastric cancer in Vietnam.

INTRODUCTION: This research aimed to determine the association of the combination of H. pylori infection and TP53 codon 72 polymorphism with non-cardia gastric cancer (GC) in Vietnam. METHODOLOGY: A total of 164 patients with non-cardia GC and 164 patients with peptic ulcer disease or functional dyspepsia in controls matched by sex and age were enrolled. H. pylori infection was diagnosed by rapid urease test and polymerase chain reaction (PCR). The cagA gene-positivity and vacA sm subtypes were determined by multiplex PCR. Genotypes of TP53 codon 72 polymorphism were determined by PCR-restriction fragment length polymorphism. RESULTS: The prevalence of H. pylori infection in GC and control group were 61.6% and 55.4%, respectively. The rates of cagA-positive strains in the two H. pylori-positive groups were 80.2% and 71.4%, respectively. There was no statistically significant difference in TP53 codon 72 genotype distribution between GC group (frequencies of Arg/Arg, Arg/Pro and Pro/Pro genotypes were 31.1%, 43.3% and 25.6%, respectively) and controls (29.3%, 52.4% and 18.3%, respectively), p = 0.172. The significant difference in genotype distribution was observed in recessive model (Pro/Pro vs Arg/Arg + Arg/Pro) when stratifying by H. pylori infection (OR = 2.02, 95% CI 1.03-3.96, p = 0.041) and by cagA-positivity (OR = 2.33, 95% CI 1.07-5.07, p = 0.032). CONCLUSIONS: This study suggests a synergistic interaction between H. pylori infection, especially cagA-positive H. pylori, and Pro/Pro genotype of TP53 codon 72 polymorphism might play a significant role in the pathogenesis of GC in the Vietnamese population.

TP53 codon 72 Polymorphism and bladder cancer risk: a meta-analysis and emphasis on the role of tumor or smoking status.

Background: Various studies had explored the relationship between TP53 codon 72 polymorphisms and the risk of bladder cancer (BC). However, their results remained inconsistent and the definite role of smoking or tumor status associated with this polymorphism in BC cases was seldom involved. Hence, this meta-analysis was to disclose such associations. Methods: Systematical and comprehensive retrieval of online databases PubMed, PMC, EMBASE and Web of Science were conducted to obtain eligible studies, up to May 30th, 2018. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were utilized to assess the associations between TP53 codon 72 polymorphisms and BC susceptibilities under five genetic comparison models. Results: Ultimately, this meta-analysis enrolled 22 applicable studies with 3,791 BC cases and 4,917 controls. Our results suggested that the variant genotypes were associated with BC risk in Asian subgroup (allele model: OR=1.19, 95% CI=1.04-1.34; dominant model: OR=1.27, 95% CI=1.06-1.52; homozygote model: OR=1.36, 95% CI=1.03-1.80), while negative outcomes were presented in Caucasians. In the relationship between TP53 codon 72 polymorphisms and BC tumor stage in Asian group, positive results were presented in allele model: OR=1.68, 95% CI=1.04-2.72; dominant model: OR=2.46, 95% CI=1.08-5.61; heterozygous model: OR=2.32, 95% CI=1.04-5.14; homozygote model: OR=2.66, 95% CI=1.04-6.81. However, no evidence was revealed between this polymorphism and BC tumor grade. Besides, significant associations were displayed between TP53 codon 72 polymorphism and smoking status (allele model: OR=1.40, 95% CI=1.06-1.84; dominant model OR=1.72, 95% CI=1.18-2.50; heterozygous model: OR=1.77, 95% CI=1.19-2.64). Conclusion: Taken together, our results shed light on that TP53 codon 72 polymorphism was significantly associated with the susceptibility to BC in Asians. In addition, positive associations were also revealed between this polymorphism and tumor stage/smoking status in BC cases.

Meta-Analysis Results on the Association Between TP53 Codon 72 Polymorphism With the Susceptibility to Oral Cancer.

Objectives: TP53 is an important tumor suppressor gene to maintain genomic integrity, and its mutations increase the susceptibility to oral carcinoma. Previous published studies have reported the relation of TP53 codon 72 polymorphism with the risk of oral carcinoma, but the results remain controversial and inconclusive. Methods: We therefore utilized meta-analysis based on a comprehensive search in PubMed, EMBASE, and Google of Scholar databases up to August 19, 2017. Results: Total 3,525 cases and 3,712 controls from 21 case-control studies were selected. We found no significant association between TP53 codon 72 polymorphism and oral carcinoma susceptibility in all genetic contrast models, including subgroup analysis based on control source and ethnicity. Furthermore, TP53 codon 72 polymorphism was not significant associated with oral carcinoma susceptibility in tobacco or alcohol use, and HPV infection status. Our results were confirmed by sensitivity analysis and no publication bias was found. Conclusions: Taken together, our data indicate that TP53 codon 72 polymorphism is not associated with the susceptibility to oral carcinoma.

Association of mRNA expression of TP53 and the TP53 codon 72 Arg/Pro gene polymorphism with colorectal cancer risk in Asian population: a bioinformatics analysis and meta-analysis.

BACKGROUND: The relationship between TP53 codon 72 Pro/Arg gene polymorphism and colorectal cancer risk in Asians is still controversial, and this bioinformatics analysis and meta-analysis was performed to assess the associations. METHODS: The association studies were identified from PubMed, and eligible reports were included. RevMan 5.3.1 software, Oncolnc, cBioPortal, and Oncomine online tools were used for statistical analysis. A random/fixed effects model was used in meta-analysis. The data were reported as risk ratios or mean differences with corresponding 95% CI. RESULTS: We confirmed that TP53 was associated with colorectal cancer, the alteration frequency of TP53 was 53% mutation and 7% deep deletion, and TP53 mRNA expression was different in different types of colorectal cancer based on The Cancer Genome Atlas database. Then, 18 studies were included that examine the association of TP53 codon 72 gene polymorphism with colorectal cancer risk in Asians. The meta-analysis indicated that TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asian population, but Arg/Arg genotype was not (Pro allele: odds ratios [OR]=1.20, 95% CI: 1.06 to 1.35, P=0.003; Pro/Pro genotype: OR=1.39, 95% CI: 1.15 to 1.69, P=0.0007; Arg/Arg genotype: OR=0.86, 95% CI: 0.74 to 1.00, P=0.05). Interestingly, in the meta-analysis of the controls from the population-based studies, we found that TP53 codon 72 Pro/Arg gene polymorphism was associated with colorectal cancer risk (Pro allele: OR=1.33, 95% CI: 1.15 to 1.55, P=0.0002; Pro/Pro genotype: OR=1.61, 95% CI: 1.28 to 2.02, P<0.0001; Arg/Arg genotype: OR=0.77, 95% CI: 0.63 to 0.93, P=0.009). CONCLUSION: TP53 was associated with colorectal cancer, but the different value levels of mRNA expression were not associated with survival rate of colon and rectal cancer. TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asians.

TP53 codon 72 polymorphism and the risk of glaucoma in a north Indian cohort: A genetic association study.

BACKGROUND: The TP53 codon 72 Proline-Arginine polymorphism (TP53 P72R) is the most widely studied candidate among those evaluated for a putative association between impaired apoptosis and glaucoma. Considering the earlier findings about enhanced apoptotic potential by the Arg variant of TP53 P72R and the conflicting results about its association with glaucoma, we initiated a hospital-based case-control association study in a north Indian cohort to investigate the association of TP53 P72R with glaucoma. MATERIALS AND METHODS: We examined the status of TP53 P72R in 139 cases of primary open angle glaucoma (POAG) and in 111 cases of primary angle closure glaucoma (PACG) with respect to 218 controls using the polymerase chain reaction-restriction fragment length polymorphism method. Logistic regression analysis including age and gender as covariates was carried out to test the association of the polymorphism with overall glaucoma, POAG, and PACG cases. RESULTS: We observed significant differences between the genotypic distributions of combined glaucoma cases and controls in the recessive model. POAG cases with respect to controls did not exhibit any significant differences in the genotypic distributions. In contrast, the genotypic distributions as per the additive and recessive models in PACG cases were significantly different from those in controls. The two models suggested an increased risk of PACG in the Arg homozygotes of the investigated cohort. CONCLUSIONS: Ours is the first study demonstrating the association of TP53 P72R with the risk of PACG. It emphasizes that apart from narrow anterior chamber angle, impaired apoptotic mechanisms could also be an important contributor toward PACG.

Association of TP53 codon 72 and CDH1 genetic polymorphisms with colorectal cancer risk in Bangladeshi population.

Till now no pharmacogenetic study of TP53 codon 72 (Arg72Pro) and CDH1 rs16260 (-160C

The TP53 codon 72 Pro/Pro genotype may be associated with an increased lung cancer risk in North China: an updated meta-analysis.

BACKGROUND: The polymorphism of TP53 codon 72, a transversion of G to C (Arg to Pro), has been demonstrated to be associated with the risk for lung cancer. However, individual studies conducted in Chinese have provided conflicting and inconclusive findings. Thus, we performed a meta-analysis by pooling all currently available case-control studies to estimate the effect of TP53 codon 72 Arg/Pro polymorphism on the development of lung cancer in the Chinese population. MATERIAL/METHODS: Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) till 10 October 2014. Pooled ORs and 95% CIs were used to assess the strength of the associations. RESULTS: A total of 12 case-control studies including 3681 lung cancer cases and 4358 controls were involved in this meta-analysis. Overall, no significant association was found between TP53 codon 72 variation and lung cancer risk when all studies in the Chinese population pooled into this meta-analysis. However, in the subgroup analysis by geographical locations, significantly increased risk was found in the population from North China under all genetic models (Allele model, OR=1.22, 95% CI: 1.04-1.43; Dominant model, OR=1.13, 95% CI: 1.01-1.25; Recessive model, OR=1.41, 95% CI: 1.07-1.87; Homozygous model, OR=1.47, 95% CI: 1.09-1.99; Heterozygous model, OR=1.40, 95% CI: 1.04-1.89). CONCLUSIONS: This meta-analysis provides the evidence that TP53 codon 72 polymorphism may contribute to the lung cancer development in North China and studies with large sample size and gene-gene (gene-environment) interactions are warranted to verify this finding.

The TP53 Codon 72 Polymorphism and Risk of Sporadic Prostate Cancer among Iranian Patients.

BACKGROUND: The TP53 gene is one of the most frequently mutated genes amongst human malignancies, particularly TP53 codon 72 polymorphism. Furthermore, an association between the TP53 codon 72 variants and prostate cancer has been reported in several studies. Although some studies have indicated an association between the TP53 Arg/Arg variant and an increased risk for prostate cancer, other studies have shown a positive correlation between the TP53 Pro/Pro genotype instead. Therefore, to clarify if this polymorphism is associated with an increased risk of prostate cancer in Iranian men, we conducted a case-control study of 40 sporadic prostate cancer patients and 80 benign prostate hyperplasia cases. METHODS: The TP53 codon 72 was genotyped using an allele specific PCR. RESULTS: A significant association between the TP53 codon 72 genotype and prostate cancer risk was found (OR = 6.8, 95% CI = [1.8-25.1], P = 0.005). However, the results of this study did not support an association between age, the Gleason score nor TP53 genotype at codon 72 in prostate cancer patients. CONCLUSIONS: TP53 codon 72 polymorphism may have a great impact in the development of prostate cancer.

Polimorfismo del codón 72 de TP53 y riesgo de cáncer gástrico: estudio caso-control en individuos de la región centroccidental de Venezuela / TP53 codon 72 polymorphism and gastric cancer risk: a case-control study in individuals from the central-western region of Venezuela

El polimorfismo del codón 72 del gen TP53 ha sido asociado con un riesgo elevado para el desarrollo de cáncer. Este polimorfismo origina dos variantes de la proteína, una con un residuo de Arginina (CGC), y otra con Prolina (CCC). El objetivo del estudio fue analizar la asociación de este polimorfismo con el riesgo de desarrollar cáncer gástrico en individuos procedentes de la región centroccidental de Venezuela, considerada de alto riesgo para esta neoplasia maligna. El ADN fue extraído de biopsias de adenocarcinoma gástrico incluídas en parafina (n = 65) y biopsias endoscópicas de pacientes con gastritis crónica (n = 87). El polimorfismo del codón 72 de TP53 fue determinado por PCR-RFLP. Se observó un incremento significativo de la frecuencia del alelo Arg en los pacientes con cáncer gástrico (P = 0,037), originando un riesgo 4,6 veces mayor (95% IC 1,0-21,3) de desarrollar esta enfermedad. Se evidenció un incremento del genotipo Arg/Arg en adenocarcinoma gástrico poco diferenciado (OR: 3,1; 95% IC 1,0-9,2), y del genotipo Arg/Pro en adenocarcinoma de moderado/buen grado de diferenciación (OR: 3,5; 95% IC 1,1-11,0) al comparar con el grupo de cáncer gástrico, y este último también al contrastar con los individuos con gastritis crónica (OR: 2,4; 95% IC 1,1-5,2). Los resultados de este estudio sugieren que la condición de portador del alelo Arg podría estar asociado con el desarrollo de cáncer gástrico en esta región de Venezuela.

Codon 72 polymorphism of the tumor suppressor gene TP53 has been associated with a higher risk in the development of several types of cancer. The polymorphism results in a variant protein with either an arginine (CGC) or a proline residue (CCC). The aim of this study was to analyze the association of the TP53 codon 72 polymorphism with the risk of developing gastric cancer in a high-risk population from the central-western region of Venezuela. DNA was extracted from paraffin-embedded gastric adenocarcinoma biopsies (n = 65) and endoscopic biopsies from chronic gastritis patients (n = 87). TP53 codon 72 polymorphism was determined by PCR-RFLP from all samples. Patients with gastric cancer had a significantly higher frequency (P = 0.037) of the Arg allele than those with chronic gastritis. A logistic regression analysis suggested that Arg carrier individuals had a 4.6-fold higher risk (95% CI 1.0-21.3) of developing gastric cancer. An increment of the Arg/Arg genotype was observed in poor-differentiated gastric adenocarcinoma (OR: 3.1; 95% CI 1.0-9.2), and of the Arg/Pro genotype in well/ moderate-differentiated adenocarcinoma samples (OR: 3.5; 95% CI 1.1-11.0), when comparing within the gastric cancer samples; and the last group also when contrasting it with chronic gastritis patients (OR: 2.4; 95% CI 1.1-5.2). The results of this study suggest that the carriage of the Arg allele could be associated with the development of gastric cancer in this Venezuelan population.