Association of PIK3CA and MDM2 SNP309 with Cervical Squamous Cell Carcinoma in a Philippine Population.
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ABSTRACT:
SUBMITTER: Tantengco OAG
PROVIDER: S-EPMC6745237 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Publications
Association of PIK3CA and MDM2 SNP309 with Cervical Squamous Cell Carcinoma in a Philippine Population.
Tantengco Ourlad Alzeus G OAG Nakura Yukiko Y Yoshimura Michinobu M Llamas-Clark Erlidia F EF Yanagihara Itaru I
Asian Pacific journal of cancer prevention : APJCP 20190701 7
Background: PIK3CA and MDM2 SNP309 have been studied to be associated with cervical cancer. PIK3CA mutation is associated with poor treatment response and low survival rate while MDM2 is associated with tumorigenesis and poor prognosis in cervical cancer. Thus, we determined the prevalence of PIK3CA and MDM2 mutations in Filipino cervical cancer patients. Methods: Twenty-eight formalin-fixed paraffin-embedded cervical squamous cell carcinoma and 16 non-malignant cervix tissue biopsies of Filipin ...[more]
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Project description:AimTo investigate the risk association and compare the onset age of hepatocellular carcinoma (HCC) patients in Taiwan with different genotypes of MDM2-SNP309.MethodsWe analyzed MDM2-SNP309 genotypes from 58 patients with HCC and 138 cancer-free healthy controls consecutively. Genotyping of MDM2-SNP309 was conducted by restriction fragment length polymorphism assay.ResultsThe proportion of homozygous MDM2-SNP309 genotype (G/G) in cases and cancer-free healthy controls was similar (17.2% vs 16.7%). Multivariate analysis showed that the risk of G/G genotype of MDM2-SNP309 vs wild-type T/T genotype in patients with HCC was not significant (OR = 1.265, 95% CI = 0.074-21.77) after adjustment for sex, hepatitis B or C virus infection, age, and cardiovascular disease/diabetes. Nevertheless, there was a trend that GG genotype of MDM2-SNP309 might increase the risk in HCC patients infected with hepatitis virus (OR = 2.568, 95% CI = 0.054-121.69). Besides, the homozygous MDM2-SNP309 genotype did not exhibit a significantly earlier age of onset for HCC.ConclusionCurrent data suggest that the association between MDM2-SNP309 GG genotype and HCC is not significant, while the risk may be enhanced in patients infected by hepatitis virus in Taiwan.
| S-EPMC2785064 | biostudies-literature
Project description:Epidemiological studies have determined the associations between polymorphisms on the promoter of MDM2 (SNP309) and the codon 72 on exon 4 of p53 (p53 Arg72Pro) and the risk of hepatocellular carcinoma (HCC); however, the results were not always consistent. The aim of the present meta-analysis was to evaluate the overall associations between these 2 variants and HCC risk.The MEDLINE, Web of science, EMBASE, Cochrane Library, and CNKI databases were searched for eligibility studies and the data were synthesized under the fixed- or random-effects model. Heterogeneity among the studies was evaluated with the Cochrane test Q and I statistic.For MDM2 SNP309, the pooled odds ratio (OR) from 15 independent studies with a total of 4038 cases and 5491 controls suggested a significant association for the variant with HCC risk [allele model, G vs T: pooled OR = 1.48, 95% confidence interval (95% CI) = 1.26-1.73; pooled OR = 1.53, 95% CI = 1.26-1.81, for G/T vs T/T; pooled OR = 2.04, 95% CI = 1.54-2.71 for G/G vs T/T]. For p53 Arg72Pro, a total of 21 studies with 7285 cases and 9710 controls suggested that the variant was also associated with HCC risk under common genetic model (allele Pro vs Arg, pooled OR = 1.13, 95% CI = 1.02-1.25; Pro/Pro vs Arg/Arg, pooled OR = 1.32, 95% CI =1.06-1.64). No publication bias was found for all the meta-analysis as suggested by the Begg funnel plot and Egger tests.These results suggested that variants MDM2 SNP309 and p53 Arg72Pro are susceptibility factors for HCC; however, more studies are warranted to validate the results.
| S-EPMC6392589 | biostudies-literature
Project description:Background/aimsBangladesh is a densely populated country with an increased incidence of lung cancer, mostly due to smoking. Therefore, elucidating the association of mouse double minute 2 homolog (MDM2) single nucleotide polymorphism (SNP) 309 (rs2279744) with lung cancer risk from smoking in Bangladeshi population has become necessary.MethodsDNA was extracted from blood samples of 126 lung cancer patient and 133 healthy controls. The MDM2 SNP309 was genotyped by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP), using the restriction enzymes MspA1I. Logistic regression was then carried out to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the risk of lung cancer. A meta-analysis of SNP309 was also carried out on 12,758 control subjects and 11,638 patient subjects.ResultsIn multivariate logistic regression, significantly increased risk of lung cancer was observed for MDM2 SNP309 in the dominant model (TG + GG vs. TT: OR, 2.13; 95% CI, 1.29 to 3.53). Stratification analysis revealed that age, sex, obesity, and smoking also increases the risk of lung cancer when carrying the MDM2 SNP309. Our meta-analysis revealed that MDM2 SNP309 was considerably associated with lung cancer in Asian populations (TG + GG vs. TT: OR, 1.32; 95% CI , 1.12 to 1.56; p = 0.019 for heterogeneity).ConclusionThe MDM2 SNP309 was associated with high risk of lung cancer in Bangladeshi and Asian population, particularly with increased age, smoking, and body mass index.
| S-EPMC7214377 | biostudies-literature
Project description:The current study aims to investigate whether MDM2-SNP309 and p53R72P polymorphisms were associated with the risk of bladder cancer in Mongolian populations. These polymorphisms were evaluated in 79 controls and 63 bladder cancer cases using a PCR-restriction fragment length polymorphism assay, followed by analysis using multivariate logistic regression model and the Kaplan-Meier model to determine the odds ratio (OR) and age at onset of bladder cancer, respectively. The results revealed that the homozygous (G/G) genotype of MDM2-SNP309 increased the risk of bladder cancer compared to the wild-type (T/T) genotype [OR=1.629; 95% confidence interval (CI)=0.622-4.266] among Mongolians. On the other hand, the homozygous (P/P) genotype of p53R72P tended to protect the population from bladder cancer compared with the wild-type (R/R) genotype (OR=0.445; 95% CI=0.1727-2.147). It also showed that G/G genotype of MDM2-SNP309 increased the risk of bladder cancer when combined with the R/R genotype of p53R72P (OR=3.355; 95% CI=0.3914-28.766). Stratification by smoking and history of chronic urinary tract diseases tended towards increasing the risk association of the G/G (OR=2.3704; 95% CI=0.4308-3.044) and T/G genotypes (OR=5; 95% CI=0.8442-30.4088) of MDM2-SNP309 with bladder cancer, respectively. The protective role of P/P of p53R72P remained following stratification. MDM2-SNP309 and p53R72P were not involved in early age onset of bladder cancer in Mongolian patients. Taken together, MDM2-SNP309 and p53R72P had no significant association with bladder cancer in Mongolian patients. The two SNPs were also not able to predict early age at onset of bladder cancer.
| S-EPMC5530310 | biostudies-literature
Project description:Recent studies have reported high frequencies of somatic mutations in the phosphoinositide-3-kinase catalytic alpha (PIK3CA) gene in several human solid tumors. Although gene amplifications of PIK3CA have been reported in head and neck squamous cell carcinoma (HNSCC), small mutation of the gene has not been evaluated in HNSCC previously. In this study, we examined the mutation frequency of PIK3CA in HNSCC.More than 75% of the somatic mutations of PIK3CA are clustered in the helical (exon 9) and kinase domains (exon 20). To investigate the possible role of PIK3CA in HNSCC tumorigenesis, exons 1, 4, 5, 6, 7, 9, and 20 of the gene were analyzed by direct genomic DNA sequencing in 38 HNSCC specimens.We identified four missense mutations in the seven exons of PIK3CA from 38 HNSCC specimens (11%). Three of the four mutations (i.e., H1047R, E542K, and E545K) have been previously reported as hotspot mutations. The remaining novel mutation, Y343C, is identified at exon 4 nucleotide 1028 A --> G. Three of the four mutations were shown to be somatic, whereas the fourth mutation (H1047R) was identified in a cell line. Interestingly, three of the four mutations identified were in pharyngeal cancer samples.These data provide evidence that oncogenic properties of PIK3CA contribute to the carcinogenesis of human head and neck cancers, especially in pharyngeal cancer. A specific kinase inhibitor to PIK3CA may potentially be an effective therapeutic reagent against HNSCC or pharyngeal cancer in particular.
| S-EPMC1780023 | biostudies-other
Project description:The present study aimed to investigate the association of p73 G4C14-A4T14 polymorphism and murine double minute 2 (MDM2) 309 T/G single nucleotide polymorphisms (SNPs) with the risk of developing non-small cell lung cancer (NSCLC) in Sothern China. The p73 and MDM2 genotypes of peripheral blood DNA from 186 patients with NSCLC and 196 normal controls were detected by polymerase chain reaction (PCR) with confronting two-pair primers (CTPP) and high resolution melting (HRM), respectively. The results of genotyping were consistent with those of direct sequencing. The p73 AT/AT [odds ratio (OR)=0.46; 95% confidence interval (CI)=0.22-0.97] and MDM2 TT (OR=0.48; 95% CI=0.26-0.86) genotypes were associated with a decreased risk of developing NSCLC compared with that of the p73 GC/GC and MDM2 GG genotypes, respectively. In addition, the interaction between the p73 and MDM2 polymorphisms reduced the risk of developing NSCLC in multiple ways (OR=0.13; 95% CI=0.03-0.59) for subjects carrying both the p73 AT/AT and MDM2 TT genotypes. Therefore, the SNP in p73 G4C14-A4T14 and the MDM2 309 polymorphism may be markers of genetic susceptibility to NSCLC in a Chinese population, and there is a possible gene-gene interaction involved in the incidence of NSCLC.
| S-EPMC5529775 | biostudies-literature
Project description:In certain cancers, MDM2 SNP309 has been associated with early tumor onset in women. In melanoma, incidence rates are higher in women than in men among individuals less than 40 years of age, but among those older than 50 years of age, melanoma is more frequent in men than in women. To investigate this difference, we examined the association among MDM2 SNP309, age at diagnosis, and gender among melanoma patients.Prospectively enrolled melanoma patients (N = 227) were evaluated for MDM2 SNP309 and the related polymorphism, p53 Arg72Pro. DNA was isolated from patient blood samples, and genotypes were analyzed by PCR-restriction fragment length polymorphism. Associations among MDM2 SNP309, p53 Arg72Pro, age at diagnosis, and clinicopathologic features of melanoma were analyzed.The median age at diagnosis was 13 years earlier among women with a SNP309 GG genotype (46 years) compared with women with TG+TT genotypes (59 years; P = 0.19). Analyses using age dichotomized at each decade indicated that women with a GG genotype had significantly higher risks of being diagnosed with melanoma at ages <50 years compared with women >or=50 years, but not when the comparison was made between women <60 and >or=60 years. At ages <50 years, women with a GG genotype had a 3.89 times greater chance of being diagnosed compared with women with TG+TT genotypes (P = 0.01). Similar observations were not seen among men.Our data suggest that MDM2 may play an important role in the development of melanoma in women. The MDM2 SNP309 genotype may help identify women at risk of developing melanoma at a young age.
| S-EPMC3881546 | biostudies-literature
Project description:BackgroundUrinary bladder carcinoma stage T1 is an unpredictable disease that in some cases has a good prognosis with only local or no recurrence, but in others can appear as a more aggressive tumor with progression to more advanced stages. The aim here was to investigate stage T1 tumors regarding MDM2 promoter SNP309 polymorphism, mutations in the p53 gene, and expression of p53 and p16 measured by immunohistochemistry, and subsequently relate these changes to tumor recurrence and progression. We examined a cohort of patients with primary stage T1 urothelial carcinoma of the bladder and their tumors.MethodsAfter re-evaluation of the original slides and exclusions, the study population comprised 141 patients, all with primary stage T1 urothelial carcinoma of the bladder. The hospital records were screened for clinical parameters and information concerning presence of histologically proven recurrence and progression. The paraffin-embedded tumor material was evaluated by immunohistochemistry. Any mutations found in the p53 gene were studied by single-strand conformation analysis and Sanger sequencing. The MDM2 SNP309 polymorphism was investigated by pyrosequencing. Multivariate analyses concerning association with prognosis were performed, and Kaplan-Meier analysis was conducted for a combination of changes and time to progression.ResultsOf the 141 patients, 82 had at least one MDM2 SNP309 G allele, and 53 had a mutation in the p53 gene, but neither of those anomalies was associated with a worse prognosis. A mutation in the p53 gene was associated with immunohistochemically visualized p53 protein expression at a cut-off value of 50%. In the group with p53 mutation Kaplan-Meier analysis showed higher rate of progression and shorter time to progression in patients with immunohistochemically abnormal p16 expression compared to them with normal p16 expression (p = 0.038).ConclusionsMDM2 SNP309 promoter polymorphism and mutations in p53 were not associated with worse prognosis in this cohort of patients with primary stage T1 urinary bladder carcinoma. However, patients with abnormal p16 expression and a mutated p53 gene had a higher rate of and a shorter time to progression, and p53 gene mutation was associated with an abnormal immunohistochemistry for p53 at a cut-off of 50%.
| S-EPMC3574032 | biostudies-literature
Project description:The incidence of endometrial cancer, a common gynecological malignancy, is increasing in Japan. We have previously shown that the ER/MDM2/p53/p21 pathway plays an important role in endometrial carcinogenesis. In the present study, we investigated the effects of germline single nucleotide polymorphisms in murine double minute 2 (MDM2) SNP309, TP53 Arg72Pro, ESR1 PvuII and XbaI, and p21 codon 31 on endometrial cancer risk. We evaluated these polymorphisms in DNA samples from 125 endometrial cancer cases and 200 controls using polymerase chain reaction-based restriction fragment length polymorphism. The association of each genetic polymorphism with endometrial cancer was examined by the odds ratio and 95% confidence interval, which were obtained using logistic regression analysis. The SNP309 GG genotype non-significantly increased the risk of endometrial cancer. The 95% confidence interval for the GG genotype vs. the TT genotype of MDM2 SNP309 was 1.76 (0.93-3.30). Endometrial cancer was not associated with tested SNP genotypes for TP53, ESR1 and p21. The combination of SNP309 GG + TG and TP53 codon 72 Arg/Arg significantly increased endometrial cancer risk. The adjusted OR was 2.53 (95% confidence interval, 1.03-6.21) and P for the interaction was 0.04. This result was supported by in vitro data showing that endometrial cancer cell lines with the SNP309 G allele failed to show growth inhibition by treatment with RITA, which reduces p53-MDM2 binding. The presence of the SNP309 G allele and TP53 codon 72 Arg/Arg genotype is associated with an increased risk of endometrial cancer in Japanese women.
| S-EPMC3729233 | biostudies-literature
Project description:BACKGROUND:Murine double minute 2 homolog (MDM2) plays an important role in the downregulation of P53 tumor suppressor gene. MDM2 inhibits P53 transcriptional activity and thereby results in accelerated tumor formation. Overexpression of MDM2 has been found in several cancer types including endometrial cancer. SNP309 is located in the promoter region of MDM2 and contributes to the overexpression of MDM2. The association between MDM2 SNP309 polymorphism and endometrial cancer risk has been investigated in several studies; however, the conclusion remains controversial. OBJECTIVES:We performed the present meta-analysis to give a comprehensive conclusion of the association between MDM2 SNP309 polymorphism and endometrial cancer susceptibility. METHODS:We conducted a literature research on PubMed, Embase, Cochrane Library, OVID, Web of Science, Wan Fang, CNKI, and CQVIP databases up to July 31, 2018. Newcastle-Ottawa scale was used to assess the quality of studies. We evaluated the strength of association by combining odds ratios (ORs) and 95% confidence intervals (CIs) in 5 different genetic models under a fixed-effect model or random-effect model. We further conducted subgroup analysis by ethnicity, source of control, histological type, clinical type, grade, and stage of tumor. Sensitivity analysis and publication bias were also performed. RESULTS:Nine eligible studies were finally included in our meta-analysis. We found MDM2 SNP309 polymorphism increased the risk of endometrial cancer under allele model (OR: 1.23, 95% CI: 1.06-1.41, P?=?.005), homozygote model (OR: 1.43, 95% CI: 1.13-1.81, P?=?.003) and recessive model (OR: 1.55, 95% CI: 1.17-2.04, P?=?.002). Subgroup analysis suggested a similar elevated risk in both Asians and Caucasians. We identified a strong association of enhanced susceptibility to endometrial cancer in endometrioid group (OR: 2.13, 95% CI: 1.28-3.54, P?=?.004) and Type I group (OR: 1.89, 95% CI: 1.25-2.86, P?=?.002) under dominant model. We identified no significant publication bias according to Egger's test. CONCLUSIONS:Our meta-analysis suggested that MDM2 SNP309 polymorphism increased the risk of endometrial cancer significantly, especially in endometrioid and Type I endometrial cancer, indicating MDM2 could serve as a potential diagnostic factor marker for endometrial cancer.
| S-EPMC6310604 | biostudies-other