Dataset Information

TP53 and MDM2 polymorphisms and the risk of endometrial cancer in postmenopausal women.

ABSTRACT: The aim of the study was to determine an association of TP53 codon 72 (Arg72Pro, G>C transversion, rs1042522) and MDM2 SNP309 (T>G change, rs2279744) polymorphisms in endometrial cancer (EC) of postmenopausal women, regarding grading and staging of EC. In the study, endometrial samples from 202 postmenopausal female patients (the study group, n = 152, was women with EC; the control group, n = 50, cancer-free patients) were taken for the evaluation of two gene polymorphisms: TP53 codon 72 and MDM2 SNP309, respectively. Genotypic analyses were performed using the PCR-RFLP technique. There were significant differences in the frequency of TP53 and MDM2 genotypes in EC patients-increased EC occurrence was observed with the presence of MDM2 G/G and TP53 Arg/Arg genotypes, while allele Pro of TP53 decreased cancer risk. Analysis of combined MDM2/TP53 polymorphisms revealed that T/T-Pro/Arg genotype decreased EC risk, whereas G/G-Arg/Arg genotype increased it. Association of these genetic polymorphisms with histological grading showed increased MDM2 G/G homozygote and TP53 Arg/Arg homozygote frequencies in grading 2 as well as allele G overrepresentation in G1 and G3 EC patients. Finally, with clinical FIGO staging under evaluation, an increase in MDM2 G/G and TP53 Arg/Arg homozygote frequencies in staging I and TP53 Arg/Arg homozygote frequencies in staging II were observed. Co-occurrence of some MDM2 SNP309 and TP53 codon 72 polymorphisms seems to influence EC risk, involving grading and staging of this neoplasm at the same time.

SUBMITTER: Zajac A

PROVIDER: S-EPMC4197345 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundDisinfection byproducts (DBPs) and N-nitroso compounds (NOC), formed endogenously after nitrate ingestion, are suspected endometrial carcinogens, but epidemiological studies are limited.ObjectivesWe investigated the relationship of these exposures with endometrial cancer risk in a large prospective cohort.MethodsAmong postmenopausal women in the Iowa Women's Health Study cohort, we evaluated two major classes of DBPs, total trihalomethanes (TTHM) and five haloacetic acids (HAA5), and nitrate-nitrogen (NO3-N) in public water supplies (PWS) in relation to incident primary endometrial cancer (1986-2014). For women using their PWS >10y at enrollment (n=10,501; cases=261), we computed historical averages of annual concentrations; exposures were categorized into quantiles and when possible ≥95th percentile. We also computed years of PWS use above one-half the U.S. maximum contaminant level (>½ MCL; 40μg/L TTHM; 30μg/L HAA5; 5mg/L NO3-N). Dietary nitrate/nitrite intakes were estimated from a food frequency questionnaire. We estimated hazard ratios (HR) and 95% confidence intervals (CI) via Cox models adjusted for age, endometrial cancer risk factors [e.g., body mass index, hormone replacement therapy (HRT)], and mutually adjusted for DBPs or NO3-N. We evaluated associations for low-grade (cases=99) vs. high-grade (cases=114) type I tumors. We assessed interactions between exposures and endometrial cancer risk factors and dietary factors influencing NOC formation.ResultsHigher average concentrations of DBPs (95th percentile: TTHM ≥93μg/L, HAA5 ≥49μg/L) were associated with endometrial cancer risk (TTHM: HR95vsQ1=2.19, 95% CI: 1.41, 3.40; HAA5: HR95vsQ1=1.84, 95% CI: 1.19, 2.83; ptrend<0.01). Associations were similarly observed for women greater than median years of PWS use with levels >½ MCL, in comparison with zero years (TTHM: HR36+vs0y=1.61, 95% CI: 1.18, 2.21; HAA5: HR38+vs0y=1.85, 95% CI: 1.31, 2.62). Associations with DBPs appeared stronger for low-grade tumors (TTHM: HRQ4vsQ1=2.12, 95% CI: 1.17, 3.83; p-trend=0.008) than for high-grade tumors (TTHM: HRQ4vsQ1=1.40, 95% CI: 0.80, 2.44; p-trend=0.339), but differences were not statistically significant (p-heterogeneity=0.43). Associations with TTHM were stronger among ever HRT users than non-HRT users (p-interaction<0.01). We observed no associations with NO3-N in drinking water or diet.DiscussionWe report novel associations between the highest DBP levels and endometrial cancer for our Iowa cohort that warrant future evaluation. https://doi.org/10.1289/EHP10207.

Dataset Information

TP53 and MDM2 polymorphisms and the risk of endometrial cancer in postmenopausal women.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets