TP53 Arg72Pro Polymorphism Research Articles

Association of miR-34b/c rs4938723 and TP53 Arg72Pro Polymorphisms with Neuroblastoma Susceptibility: Evidence from Seven Centers

Neuroblastoma is a pediatric malignancy arising from the developing peripheral nervous system. p53 and downstream effector miR-34b/c have critical tumor suppressing functions. TP53 Arg72Pro (rs1042522 C > G) and miR-34b/c rs4938723 (T > C) polymorphisms have been known to modify cancer susceptibility. This study was performed to validate the association of these two polymorphisms and neuroblastoma risk with 819 cases and 1780 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to assess the strength of the associations. False positive report possibility analysis was adopted to dissect out real significant associations from chance findings. We found that both TP53 Arg72Pro (CG/GG vs. CC: adjusted OR = 0.82, 95% CI = 0.69-0.98) and miR-34b/c rs4938723 (TC/CC vs. TT: adjusted OR = 0.64, 95% CI = 0.54-0.75) were associated with decreased neuroblastoma susceptibility. Stratify analyses further confirmed the protective effect among some subgroups. Moreover, subjects with variant alleles of both polymorphisms were associated with more significantly decreased neuroblastoma risk (CG/TC vs. CC/TT: adjusted OR = 0.38, 95% CI = 0.28-0.50; GG/TC vs. CC/TT: adjusted OR = 0.43, 95% CI = 0.30-0.63) than those carrying variant allele of either one polymorphism (CC/TC vs. CC/TT: adjusted OR = 0.51, 95% CI = 0.37-0.69; CG/TT vs. CC/TT: adjusted OR = 0.71, 95% CI = 0.55-0.92), suggesting cumulative effects of the polymorphisms. False positive report possibility analysis further verified that our findings are noteworthy. Overall, we confirmed that miR-34b/c rs4938723 and TP53 Arg72Pro conferred decreased neuroblastoma risk and two polymorphisms exerted stronger protective effects against neuroblastoma than either one alone.

Assessment of Individual Radiosensitivity in Inhabitants of Takandeang Village － A High Background Radiation Area in Indonesia

People living in high background radiation area (HBRA) possibly developed the radioadaptive response (RAR) phenomena. Mamuju area in West Sulawesi Indonesia also known as the HBRA in Indonesia due to high natural uranium contents. It is possible that RAR was developed in Mamuju inhabitants. To prove this hypothesis, here in this study evaluation of the individual radiosensitivity in Takandeang Village, Mamuju inhabitants using G 2 micronucleus (MN) assay was conducted. Association between blood groups and TP53 Arg72Pro polymorphism with individual radiosensitivity also evaluated in this study. Using G 2 MN assay we assessed the individual radiosensitivity of Takandeang Village inhabitants and control samples. For each sample, three parameters were calculated. The spontaneous (baseline) MN number, MN number after 0.5 Gy in vitro irradiation and radiation induced MN were calculated to predict the individual radiosensitivity. The radiation induced MN was defined by subtracting the spontaneous MN number from the MN number after irradiation. The mean and SD of the number of micronucleus induced by radiation found in control group (CG) was set as the cut-off value to determine the individual radiosensitivity in all samples. The radiation induced MN higher than the mean CG + 1SD CS was scored as 1, indicating a milder radiosensitive phenotype, whereas a result higher than the mean CG + 2SD CG was scored as 2, and indicated a more severe radiosensitive phenotype. When the individual value was lower than the mean CG + 1SD CG, a score of 0 was attributed to the tested subject. Results showed that four individuals in Takandeang Village inhabitants were having a milder radiosensitive phenotype, whilst the other was categorized as normal radiosensitive. The similar finding also found in control samples. Our study failed to find a correlation between radiosensitivity and blood group also the TP53 Arg72Pro polymorphism. Overall our study revealed the possibility of RAR phenomena in Takandeang Village inhabitants. Further investigation using a different point of radiation dose value and larger sample number should be performed to validate this study results.

Meta-analysis for the association between TP53 Arg72Pro polymorphism and human thyroid cancer risk

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 2 112 thyroid cancer cases and 4 000 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 among total population, but not medullary thyroid carcinomas. Conclusion There is a significant association between Arg72Pro polymorphism in TP53 gene 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. Key words: Thyroid cancer; Arg72Pro; TP53; Gene polymorphism; Meta-analysis

Polymorphisms in MDM2 and TP53 Genes and Risk of Developing Therapy-Related Myeloid Neoplasms

One of the most severe complications after successful cancer therapy is the development of therapy-related myeloid neoplasms (t-MN). Constitutional genetic variation is likely to impact on t-MN risk. We aimed to evaluate if polymorphisms in the p53 pathway can be useful for predicting t-MN susceptibility. First, an association study revealed that the Pro variant of the TP53 Arg72Pro polymorphism and the G allele of the MDM2 SNP309 were associated with t-MN risk. The Arg variant of TP53 is more efficient at inducing apoptosis, whereas the Pro variant is a more potent inductor of cell cycle arrest and DNA repair. As regards MDM2 SNP309, the G allele is associated with attenuation of the p53 apoptotic response. Second, to evaluate the biological effect of the TP53 polymorphism, we established Jurkat isogenic cell lines expressing p53Arg or p53Pro. Jurkat p53Arg cells presented higher DNA damage and higher apoptotic potential than p53Pro cells, after treatment with chemotherapy agents. Only p53Pro cells presented t(15;17) translocation and del(5q). We suggest that failure to repair DNA lesions in p53Arg cells would lead them to apoptosis, whereas some p53Pro cells, prone to cell cycle arrest and DNA repair, could undergo misrepair, generating chromosomal abnormalities typical of t-MN.

Association of the TP53 rs1042522 C>G polymorphism and hepatoblastoma risk in Chinese children.

The TP53 gene encodes an important class of cell cycle and tumor-suppressing factors that play critical roles in maintaining genomic stability. The TP53 Arg72Pro (rs1042522 C>G) polymorphism has been reported to be associated with the risk of several types of adult cancers; however, its risk for pediatric cancers remains unclear. Here, we analyzed the association of the TP53 gene rs1042522 C>G polymorphism with hepatoblastoma (HB) susceptibility in a hospital-based study among Chinese children. A total of 213 HB patients and 958 healthy controls were enrolled in the study. Genotypes were determined by a TaqMan assay, and the strength of the association was assessed by the odds ratios and 95% confidence intervals generated from logistic regression models, adjusted for age, gender, and clinical stage. No significant association between the TP53 rs1042522 C>G polymorphism and HB susceptibility was detected in the main analysis or in stratification analyses of age, gender, and clinical stages. Overall, the TP53 gene rs1042522 C>G polymorphism is not associated with HB susceptibility in the Chinese population, other polymorphisms alone or in combination should be investigated to further clarify HB susceptibility.

Association Between Genetic Variant in the Promoter of Pri-miR-34b/c and Risk of Glioma.

Growing evidence indicates that p53 can regulate the expression of miRNAs, particularly the miR-34 family members, which are described as potential tumor suppressors. Loss of miR-34 suppresses TP53-mediated cell death, whereas over expression of miR-34 induced apoptosis. The study designed to investigate the association between the pir-miR-34b/c rs4938723, TP53 Arg72Pro and the risk of glioma. We genotyped the two polymorphisms in175 glioma patients and 235 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing assay. Association analysis showed that the CC genotype of the pir-miR-34b/c rs4938723 was associated with a significantly decreased risk of glioma compared to the TT genotype (CC vs. TT: adjusted OR = 0.43;95% CI, 0.21–0.87,P = 0.02). Moreover, a significant association between the patients with glioma and controls was also observed in a recessive model (OR = 0.41; 95% CI, 0.21–0.81, P = 0.007). In contrast, the CC genotype of the TP53 Arg72Pro was associated with a significantly increased risk of glioma compared to the GG genotype (CC vs. GG: adjusted OR = 1.73;95% CI, 1.04–2.89,P = 0.04), and a significant association between the patients with glioma and controls was also observed in a recessive model (OR = 2.00; 95% CI, 1.26–3.18, P = 0.003). These findings suggest that the pri-miR-34b/c rs4938723CC and TP53 Arg72-Pro polymorphisms may be associated with the risk of glioma.

Association of TP53 Arg72Pro polymorphism (rs1042522) with bladder cancer risk in the Ukrainian population

Aim. To determine the frequency of TP53 polymorphic variants in bladder cancer patients and define possible association of this polymorphism with a bladder cancer in Ukrainians patients. Methods. The genotypes of TP53 gene at codon 72 were detected by PCR with allele specific primers. We investigated Arg72Pro polymorphism in 114 DNA samples of patients with bladder cancer. The PCR-amplified DNA products were subjected to electrophoresis in 3 % agarose. Results. The distribution of genotypes in group of patients with a bladder cancer was: Arg/Arg – 59.6 % (n=68), Arg/Pro – 40.4 % (n=46), Pro/Pro – 0 % (n=0). Genotype frequencies in patients (χ2=7.28, p=0.0007) weren’t in agreement with Hardy-Weinberg equilibrium. There were significant differences in the frequency of genotypes between the healthy individuals and the cancer group patients. Our result showed that patients with bladder cancer had a significantly higher frequency of Arg/Arg (F=42.7, p<0.05) and a lower frequency of Pro/Arg (F=40.9, p<0.05) compared to controls. Conclusions. Our study allows us to suggest that Arg/Arg polymorphic variant of TP53 is associated with the higher risk of bladder cancer development in the Ukrainian population (OR = 5,6, 95 % CI = 3.19 to 9.34, p < 0.0001). Keywords: TP53 gene, bladder cancer, polymorphism Arg72Pro, Ukrainian population.

POLYMORPHISM OF THE TP53 GENE IN PATIENTS WITH GASTRIC CANCER IN PROSPECTIVE AND CLINICAL CASE-CONTROL STUDIES

Background.A functionally significant TP53Arg72Pro polymorphism can contribute to the development of gastric cancer (GC).The aim:to study the associations of genotypes and alleles of the TP53Arg72Pro 4 polymorphism with GC and biomarkers of gastric ucosal atrophy in population-based prospective and case-control clinical trials among the population of Siberia.Material and methods.As a part of the epidemiological study, data of the international multicenter HAPIEE project for 2003–05, based on a population sample of residents of Novosibirsk city (serum and DNA samples) and data of the population-based registry of GC (2012) were compared. Gastric cancer patients were matched by age and sex to HAPIEE population controls. A total of 156 serum samples (GC – 52, control – 104) and 146 DNA samples (GC – 50, control – 96) were available for prospective analysis. DNA samples from 80 gastric cancer patients (45 men and 35 women, mean age 61.0 ± 13.4 years) and from 87 age-and sex-matched controls were analyzed. DNA samples from venous blood were genotyped according to standard methods. Serum samples were tested using diagnostic kit for enzyme-linked immunosorbent assays to determine the levels of pepsinogen I (PGI), PGII, PGI/PGII ratio, gastrin-17 and IgG antibodies to H. pylori.Results.No differences in genotype and allele frequencies of the TP53 gene between the case group and the control group were found. A decreased frequency of the Pro allele in female gastric cancer patients compared with controls indicated that the Pro allele is protective against the development of gastric cancer, but this effect was not observed in male patients. No associations of TP53 genotypes with the risk of diffuse or intestinal gastric cancer, as well as with the age and sex of patients were found. A high frequency of genotypes with the Pro allele in patients with stage III–IV gastric cancer indicated the relationship between Arg/Pro TR53 and tumor progression, in particular, the contribution of the minor Pro allele to the unfavorable prognosis. A prospective study showed high risk of reducing the level of pepsinogen for assessing predisposition to gastric cancer.Conclusion.Two case-control studies (population and clinical) conducted in the Western Siberia found no relationship between the TP53Arg72Pro polymorphism and the risk of gastric cancer. However, the TP53 genotype with a rare Pro allele was associated with atrophic gastritis and severity of gastric cancer.

Basal Cell Carcinoma Risk and TP53 Arg72Pro Polymorphism: An Algerian Population Study

Background: Basal cell carcinoma (BCC) is the commonest skin cancer in human. It is characterized by a strictly local malignity with a frequent tendency to relapse. BCC development results from the interaction between environmental factors and genetic alterations, including mutations in the TP53 gene involved in its progression and relapse. TP53 gene is named “guardian of the genome”, as it plays major roles in genomic stability. In addition to mutations, several polymorphisms had been detected in the wild-type TP53. The polymorphic variant is usually associated to BCC diseases at codon 72 of TP53 (Arg72Pro). Objectives: In the present study, we undertook a case control study to explore a possible association between TP53 Arg72Pro polymorphism and the predisposition to BCC in Northwest Algerian population. Methods: TP53 Arg72Pro polymorphism was investigated by PCR/RFLP then confirmed by DNA sequencing of 61 controls versus 50 BCC cases. Results: This study allows us to characterize BCC subgroups regarding age, tumor location, and relapse. No correlation was found between any of these criteria and each of the two variants of TP53 Arg72Pro. No association was found between TP53 Arg72Pro variants and developing BCC either (BCC group: Pro = 54%, versus Control group: Pro = 53 %, P > 0.05, OR 1.52 (0.89 - 2.60)). Finally, as expected, sun-exposure was confirmed as a risk factor for BCC. Conclusions: This study supports that analyzing TP53 Arg72Pro polymorphism is of no interest for identifying high-risk subjects for BCC in the Algerian population. Further studies are needed to explain the role of this polymorphism in genetic predisposition to BCC in some other populations.

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.

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.

Genetic polymorphisms of TP53 Arg72Pro and Pro47Ser among Egyptian patients with colorectal carcinoma

Background: Previous reports demonstrated the role of TP53 gene polymorphisms with CRC risk among several ethnic populations. The purpose of this study is to assess the association of the TP53 Arg72Pro and Pro47Ser variants with CRC risk among Egyptian patients.Subjects and Methods: This work was conducted on 120 unrelated CRC Egyptian patients who were compared to 140 healthy controls. DNA was genotyped for these variants using the PCR-RFLP technique.Results: CRC patients observed a significant association of the rare genotype of TP53 Arg72Pro polymorphism compared with healthy controls. On the contrast, all genetic models showed no statistical association of TP53 Pro47Ser polymorphism among CRC patients compared with healthy controls. On the contrast, CRC patients of the TP53 gene polymorphisms indicated no significant difference regarding their clinical and laboratory markers.Conclusions: Our findings indicate a strong association with TP53 Arg72Pro variant within increased risk of CRC among Egyptian patients.

Impact of polymorphisms of TP53 Arg72Pro, excision repair cross-complementing Protein 1 Asn118Asn (C118T) and deletion in Intron 2 of BIM in chronic myeloid leukemia patients on imatinib treatment

Background: Imatinib (IM) results in durable responses in a large number of patients with chronic myeloid leukemia (CML). However, a substantial number develops drug resistance. There could be several reasons for the heterogeneity of response. To survive genotoxic damage induced by IM, BCR-ABL1 can modulate DNA repair mechanisms, cell-cycle checkpoints, and Bcl-2 family members. Hence, we aimed to find out the impact of single-nucleotide polymorphisms mainly TP53Arg72Pro, excision repair cross-complementing protein 1 (ERCC1) Asn118Asn (C118T) and deletion in intron 2 of BIM genes in CML patients and their association with disease progression and treatment outcome. Materials and Methods: In the present study, 174 CML and 174 control samples were analyzed for polymorphisms of TP53Arg72Pro, ERCC1 C118T, and intron 2 deletion in BIM genes using polymerase chain reaction-restriction fragment length polymorphism method. Results: Genotyping of TP53Arg72Pro polymorphism showed a trend toward proline genotype/allele association with younger age (P = 0.031), advanced phase, high BCR-ABL1 expression levels and presence of tyrosine kinase domain (TKD) mutations compared to respective groups. Genotyping of ERCC1 C118T polymorphism showed a significant association of CT genotype and T allele with high BCR-ABL1 levels BIM deletion polymorphism was not observed in the present study (P = 0.030) and presence of TKD mutations (P = 0.013). The 72 proline allele and heterozygous 118CT genotype frequencies were significantly elevated in deceased patients compared to those on IM and other tyrosine kinase inhibitors treatment. Conclusion: our data suggested that proline genotype/allele of TP53Arg72Pro polymorphism possibly leading to inefficient apoptosis and 118CT genotype in ERCC1 gene with possibly less DNA repair efficiency might be responsible for the suboptimal responses to IM and poor survival in CML patients. Deletion in intron 2 of BIM gene was not observed in our study.

No association between TP53 Arg72Pro polymorphism and ovarian cancer risk: evidence from 10113 subjects.

The TP53 gene product is an important regulator of cell growth and a tumor suppressor. The association between TP53 Arg72Pro polymorphism and ovarian cancer risk has been widely investigated, but the results are contradictory. We therefore searched the PubMed, EMBASE and Chinese Biomedical databases for studies on the relation between TP53 Arg72Pro polymorphism and ovarian cancer risk. Our final meta-analysis included 24 published studies with 3271 cases and 6842 controls. Pooled results indicated that there was no significant association between TP53 Arg72Pro polymorphism and ovarian cancer risk [Pro/Pro vs. Arg/Arg: odds ratio (OR) =1.04, 95% confidence interval (CI) = 0.81-1.34; Arg/Pro vs. Arg/Arg: OR = 1.14, 95% CI = 0.96-1.36; recessive: OR = 1.05, 95% CI = 0.90-1.22; dominant: OR = 1.12, 95% CI = 0.94-1.33; and Pro vs. Arg: OR = 1.06, 95% CI=0.93-1.20]. Likewise, stratified analyses failed to reveal a genetic association. Despite some limitations, the present meta-analysis provides statistical evidence indicating a lack of association between TP53 Arg72Pro polymorphism and ovarian cancer risk.

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<A) genes has been reported on Bangladeshi population relating those with colorectal cancer. So the aim of the study is to determine whether there is an elevated risk of colorectal cancer development with TP53 codon 72 and CDH1 rs16260 genetic polymorphism in Bangladeshi population for the first time. To investigate the association of these two SNPs, we conducted a case-control study with 288 colorectal cancer patients and 295 healthy volunteers by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. We found an increased risk of association between Arg/Pro heterozygosity (adjusted OR=2.58, 95% CI=1.77–3.77, p<0.05) and Pro/Pro mutant homozygosity (adjusted OR=2.92, 95% CI=1.78–4.78, p<0.05) along with the combined genotype (Arg/Pro+Pro/Pro) (adjusted OR=2.70, 95% CI=1.90–3.82, p<0.05) and colorectal cancer predisposition. In case of CDH1 rs16260 polymorphism, C/A heterozygous and A/A mutant homozygous are significantly (p<0.05) found to be associated with colorectal cancer risk with adjusted OR of 1.94 and 2.63, respectively. The combined genotype of C/A and A/A was also found to be strongly associated with colorectal cancer risk compared to C/C genotype (adjusted OR=2.02, 95% CI=1.42–2.87, p<0.05). In conclusion, heterozygosity and mutant homozygosity as well as the combination of both TP53 Arg72Pro and CDH1 rs16260 polymorphisms are responsible to increase the risk of colorectal cancer development in Bangladeshi population.

Xenobiotic/drug metabolizing enzyme and TP53 polymorphisms and clinical outcome in advanced nonsmall cell lung cancer patients.

The association between polymorphisms of xenobiotic/drug metabolizing enzymes and TP53 and response to chemotherapy and survival of patients with nonsmall cell lung cancer (NSCLC) are limited and inconclusive. In this study, CYP2E1*5B, CYP2E1*6, CYP2E1*7B, GSTO1 (A140D), and TP53 (Arg72Pro) polymorphisms and response to platinum-based chemotherapy and survival in 137 advanced stage NSCLC patients were investigated. Genetic polymorphism analyses were determined by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). The patients with TP53 Pro/Pro variant were more likely to be resistant to chemotherapy than those with Arg/Arg variants with marginal significance (P = 0.066). We also analyzed these gene variants in combination with CYP1A1 (Ile462Val), CYP1B1 (Asn453Ser), GSTM1, GSTP1 exon 5 (Ile105Val), and GSTP1 exon 6 (Ala114Val) and GSTT1 polymorphic genes that we have previously genotyped in the same patients (Ada et al., Neoplasma, 57, 512-527, 2010). The multivariate analysis revealed that adjusted hazard ratio (HR) of death of the combined variant genotypes of TP53 (Arg72Pro, Pro72Pro) and CYP1A1 (Ile462Val, Val462Val) increased significantly as compared to wild-type genotypes (HR, 6.03; 95% CI, 1.39-26.04, P = 0.016). These results show that combined variant genotypes of TP53 (Arg72Pro, Pro72Pro) and CYP1A1 (Ile/Val, Val/Val) are associated with worsening of survival in NSCLC patients.

The association between the TP53 Arg72Pro polymorphism and colorectal cancer: An updated meta-analysis based on 32 studies.

Several previous studies evaluated the association between the Arg72Pro (rs1042522) polymorphism in the TP53 tumor suppressor gene and colorectal cancer (CRC). However, the results are conflicting. This meta-analysis aimed to shed new light on the precise association between TP53 variants and CRC. We analyzed 32 published case-control studies involving 8,586 cases and 10,275 controls using crude odd ratios (ORs) with 95% confidence intervals (CIs). The meta-analysis was performed using a fixed-effect or random-effects model, as appropriate. We found that the TP53 Arg72Pro polymorphism was not significantly associated with CRC risk in the overall population. However, subgroup analysis based on ethnicity revealed an increased risk of CRC among Asians (CC vs. GC+GG: OR=1.22, 95% CI: 1.02-1.45), and similar results were found for rectal cancer (CC vs. GC+GG: OR=1.34, 95% CI: 1.120-1.62). These results suggest that the TP53 Arg72Pro polymorphism CC genotype may contribute to an increased risk of CRC, especially for rectal cancer and among Asians.

Association between XRCC1 ARG399GLN, TP53 ARG72PRO and MDM2 T309G polymorphisms and the risk of breast cancer in women of the Kyrgyz population

Aim. To study an association between Arg399Gln of XRCC1 gene, Arg72Pro of TP53 gene and T309G of MDM2 gene polymorphisms and breast cancer (BC) rate in women of the Kyrgyz population Material and Methods. Genomic DNA was obtainedfrom the whole blood of 117 breast cancer patients and 102 cancer-free healthy women residing in the Kyrgyz Republic. XRCC1 (Arg399Gln), TP53(Arg72Pro) and MDM2 (T309G) genotyping was carried out by restriction fragment length polymorphism (RFLP) assay. Results. Women with the 399Gln allele had 1,57 fold higher risk (OR=1,57; p=0,034) of developing breast cancer than cases without these alleles. Individuals carrying the heterozygous genotype Arg399Gln had 2,77 fold higher risk (OR=2,77; p=0,0010) of BC. Notably, haplotype analyses revealed a stronger association with breast cancer risk if compare with data of the genotype analysis at each locus alone. The combination of heterozygous XRCC1 (Arg399Gln) variant and TP53 (Arg72Pro) genes increased even more the risk of BC (OR=3,98; p=0,0059). The combination of Arg399Gln and T309G genotypes of - XRCC1 and MDM2 genes is significant association with risk of BC (OR=3,0; p=0,034). We showed the combinations of Arg399Gln, Arg72Pro and T309Ggenotypes of-XRCC1, TP53 andMDM2 genes is related to the strong association with risk of BC in Kyrgyz women (OR=6,40; p=0,025). Conclusion. The polymorphisms Arg399Gln of XRCC1 gene, Arg72Pro of TP53 gene and T309G of MDM2 gene are associated with an increased risk of BC in Kyrgyz females. Combinations of unfavorable genotypes of several candidate genes increase even more the risk of BC.

Interactions of Pri-miRNA-34b/c and TP53 Polymorphisms on the Risk of Osteoporosis.

Osteoporosis (OP) is a common, multifactorial disorder. Here, we investigated the association between polymorphisms in pri-miR-34b/c (rs4938723) and TP53 (Arg72Pro) and the prevalence of OP. A total of 681 individuals were assessed in a case-control study, including 310 patients with OP and 371 controls. Variants in pri-miR-34b/c and TP53 were identified using a polymerase chain reaction-restriction fragment length polymorphism method. The presence of the CC and CT/CC pri-miR-34b/c genotypes were associated with a significantly reduced risk of OP compared with the TT genotype (CC vs. TT: odds ratio [OR] = 0.32, 95% confidence intervals [CI] = 0.17-0.59; p < 0.001; CT/CC vs. TT: OR = 0.69, 95% CI = 0.51-0.93; p = 0.016). The CC genotype was also associated with a significantly reduced OP risk compared with the TT/CT genotypes (OR = 0.35, 95% CI = 0.19-0.64; p < 0.001). Furthermore, compared with the carriers of the Arg72Pro GG genotype, carriers of the CC genotype had a 2.21-fold increased OP risk (95% CI = 1.45-3.37; p < 0.001) and CG/CC genotypes carriers had a 1.96-fold increased OP risk (95% CI = 1.39-2.76; p < 0.001). The present findings indicate that pri-miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms may contribute to the risk of OP.

Association between TP53 Arg72Pro polymorphism and leukemia risk: a meta-analysis of 14 case-control studies.

The relationship between the TP53 Arg72Pro polymorphism (rs1042522) and the risk of leukemia remains controversial. Consequently, we performed a meta-analysis to accurately evaluate the association between TP53 Arg72Pro polymorphism and leukemia risk. A comprehensive search was conducted to find all eligible studies of TP53 Arg72Pro polymorphism and leukemia risk. Fourteen case-control studies, with 2,506 cases and 4,386 controls, were selected for analysis. The overall data failed to indicate a significant association between TP53 Arg72Pro polymorphism and the risk of leukemia (C vs. G: OR = 1.09, 95% CI = 0.93–1.26; CC vs. GC + GG: OR = 1.23, 95% CI = 0.96–1.57). In a subgroup analysis of clinical types, an increased risk was observed in the acute lymphocytic leukemia (ALL) subgroup (CC vs. GC + GG: OR = 1.73; 95% CI = 1.07–2.81) but not in the acute myeloid leukemia (AML) subgroup. In the subgroup analysis, no significant associations with ethnicity and the source of the controls were observed. In conclusion, the results suggest that there is no association between TP53 Arg72Pro polymorphism and the risk of leukemia, but the CC genotype may increase the risk of ALL TP53 Arg72Pro polymorphism CC genotype may increase the risk of ALL but is not associated with AML. Further large-scale, well-designed studies are needed to confirm our results.