MTHFR polymorphisms in relation to ovarian cancer risk.
Ontology highlight
ABSTRACT:
SUBMITTER: Terry KL
PROVIDER: S-EPMC2952716 | biostudies-literature | 2010 Nov
REPOSITORIES: biostudies-literature
Publications
MTHFR polymorphisms in relation to ovarian cancer risk.
Terry Kathryn L KL Tworoger Shelley S SS Goode Ellen L EL Gates Margaret A MA Titus-Ernstoff Linda L Kelemen Linda E LE Sellers Thomas A TA Hankinson Susan E SE Cramer Daniel W DW
Gynecologic oncology 20101101 2
<h4>Objective</h4>Folate has been hypothesized to influence carcinogenesis due to its dual role in DNA methylation, which regulates gene expression, and synthesis of purine and thymidylate, which is vital for DNA repair. Thus, we examined ovarian cancer risk in relation to two functional polymorphisms (C677T and A1298C) in the MTHFR gene.<h4>Methods</h4>We genotyped the C677T (rs1801133) and A1298C (rs1801131) MTHFR polymorphisms in 1642 cases and 2068 controls from three studies, the New Englan ...[more]
Similar Datasets
Project description:ObjectiveTo examine single nucleotide polymorphism (SNPs) in MUC16 (CA125) and MUC1 (CA15.3) in relation to ovarian cancer risk and survival.MethodsWe genotyped germline variants of MUC16 (rs2547065, rs1559168, rs12984471, rs2121133) and MUC1 (rs2070803, rs4072037, rs1045253) using samples collected from 758 ovarian cancer cases and 788 controls enrolled in the New England Case-Control Study between 2003 and 2008. We calculated age-adjusted odds ratios (OR) and 95% confidence intervals (CIs) for disease risk using unconditional and polytomous logistic regression and hazard ratios (HR) for survival using Cox proportional hazard ratios. In a subset of cases, we compared log-normalized CA125 values by genotype using generalized linear models.ResultsCases homozygous for the variant allele of MUC16 SNP, rs12984471, had poorer overall survival (log-rank p = 0.03) and higher CA125 levels, especially cases over age 65 (p = 0.01). For MUC1 SNP, rs4072037, women homozygous for the G variant had a non-significantly decreased risk for serous invasive types but elevated risk for serous borderline tumors, mucinous borderline and invasive tumors, and endometrioid tumors. Women with the variant allele of MUC16 SNP, rs2547065, especially those who were homozygous had an elevated risk for ovarian cancer; but this association was not confirmed in an independent dataset.ConclusionThis targeted screen of seven polymorphisms of MUC16 and MUC1 genes failed to identify and confirm effects on ovarian cancer risk overall. However, there may be effects of MUC16 rs12984471 on survival and MUC1 rs4072037 on risk for histologic types of ovarian cancer other than invasive serous. Further study is warranted.
| S-EPMC3923771 | biostudies-literature
Project description:We recently analyzed the hypermethylation status of the p16INK4a (p16) gene promoter in normal-appearing mucosa obtained from patients with colorectal cancer. Hypermethylation of p16 was associated with reduced survival of these patients. In the present study, germ line polymorphisms in the folate- and methyl-associated genes, methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and methionine synthase reductase (MTRR), were analyzed in the same patient cohort to find a possible link between these genetic variants and p16 hypermethylation. Genomic DNA was extracted from blood of patients (n = 181) and controls (n = 300). Genotype analyses were run on an ABI PRISM(®) 7900HT sequence-detection system (Applied Biosystems), using real-time polymerase chain reaction and TaqMan chemistry. The results showed that the genotype distributions of the patient and control groups were similar. No significant differences in cancer-specific or disease-free survival of stage I-III patients according to polymorphic variants were detected, nor were any differences in cancer-specific or disease-free survival detected when patients were subgrouped according to the MTHFR or MTR genotype groups and dichotomized by p16 hypermethylation status in mucosa. However, patients with the MTRR 66 AA/AG genotypes were found to have a significantly worse cancer-specific survival when the mucosa were positive, compared with negative, for p16 hypermethylation (hazard ratio 2.7; 95% confidence interval 1.2-6.4; P = 0.023). In contrast, there was no difference in survival among patients with the MTRR 66 GG genotype stratified by p16 hypermethylation status. These results indicate a relationship between genetic germ-line variants of the MTRR gene and p16 hypermethylation in mucosa, which may affect the clinical outcome of patients with colorectal cancer.
| S-EPMC2935958 | biostudies-literature
Project description:BackgroundThe role of vitamin D receptor (VDR) single-nucleotide polymorphisms (SNPs) in ovarian cancer has been studied in various populations; however, these results are discordant between different ethnicities.MethodUsing the polymerase chain reaction-restriction fragment length polymorphism method, we studied the prevalence of the VDR FokI (rs2228570) and BsmI (rs1544410) SNPs in women with ovarian cancer (n=168) and controls (n=182) in a Polish population.ResultsWe found a significant contribution of the BsmI SNP Bb+BB-versus-bb dominant inheritance model to ovarian cancer development (p=0.0221, p(corr)=0.0442, odds ratio [OR]=1.648 [95% confidence intervals, CI=1.073-2.532]). However, we did not observe an association of the BsmI SNP BB versus Bb+bb recessive inheritance model in patients (p=0.8059, OR=1.093 [95% CI=0.538-2.218]). Moreover, there was no association of FokI SNPs either in Ff+ff versus FF dominant or ff versus Ff+FF recessive inheritance models with ovarian cancer development (p=0.9924, OR=1.002 [95% CI=0.628-1.599] and p=0.1123, OR=1.542 [95% CI=0.901-2.638], respectively). The p-values of the trend test observed for the VDR BsmI and FokI SNPs in patients with ovarian cancer were p(trend)=0.0613 and p(trend)=0.3655, respectively.ConclusionOur study indicates that the VDR B gene variant might be a moderate risk factor of ovarian cancer development in the Polish population.
| S-EPMC3582284 | biostudies-literature
Project description:Background and objectiveThe Wnt/β-catenin signaling pathway has been considered to be a factor in the development and progression of ovarian cancer.MethodsAll patients with ovarian cancer and controls were tested for BRCA1 mutations (5382incC, C61G, 4153delA) with HybProbe assays and for BRCA2 mutation (5946delT) using high-resolution melting curve analysis (HRM). Mutation carriers were excluded from the association analysis. We studied nine single nucleotide polymorphisms (SNPs) located in CTNNB1 (β-catenin) [rs4533622, rs2953], APC (rs11954856, rs351771, rs459552), and AXIN2 (rs4074947, rs7224837, rs3923087, rs2240308) in women with ovarian cancer without BRCA1/BRCA2 mutations (n = 228) and controls (n = 282). Genotyping of CTNNB1 rs4533622, rs2953, APC rs351771, AXIN2 rs4074947, rs3923087, and rs2240308 was performed by HRM, while that of APC rs11954856, rs459552 and AXIN2 rs7224837 was conducted by PCR followed by the appropriate restriction enzyme digestion [PCR–restriction fragment length polymorphism (PCR-RFLP)].ResultsThe most common BRCA1/BRCA2 mutations were identified in 30 patients with ovarian cancer. These mutations were not found in controls. The lowest p values of the trend test (p trend) were observed for the APC rs351771 and rs11954856 SNPs in patients with ovarian cancer (p trend = 0.006 and p trend = 0.007, respectively). Using a dominant inheritance model, we found that the APC rs11954856 SNP is associated with an increased risk of ovarian cancer development [odds ratio = 2.034 (95 % CI 1.302–3.178); p = 0.002]. We also observed significant allelic differences for the APC rs351771 SNP between patients and controls (p = 0.006).ConclusionOur study demonstrated significantly increased APC rs11954856 and rs351771 SNP frequencies in Polish women with ovarian cancer.
| S-EPMC3899496 | biostudies-literature
Project description:ObjectiveTo examine the relationship between polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and susceptibility to lung cancer in a female Chinese population.MethodA hospital-based case-control study of 388 cases and 388 controls was conducted. Two polymorphisms in MTHFR were detected using TaqMan methods.ResultsThe MTHFR C677T polymorphism was associated with the risk of lung cancer and lung adenocarcinoma. Carriers with the TT genotype of C677T were observed to have an increased risk of lung cancer and lung adenocarcinoma (the ORs were 1.550 and 1.588, respectively). By contrast, the A1298C polymorphism had a negative relationship with the risk of lung cancer and lung adenocarcinoma; compared with the AA genotype carriers, the CC genotype carriers had a lower risk of lung cancer and adenocarcinoma in the female Chinese population (ORs were 0.302 and 0.215, respectively). In the stratified analyses, we observed only the A1298C polymorphism in the CC genotype carriers with a statistically significant reduction in the risk of non-small-cell lung cancer, compared to the AA genotype carriers. No significant statistical association was found between the MTHFR gene polymorphisms and risk of the residual subtype of lung cancer.ConclusionThis study provides evidence that the MTHFR C677T polymorphism may contribute to the development of lung cancer and lung adenocarcinoma in a female Chinese population. However, the MTHFR A1298C polymorphism may be associated with the decreasing risk of lung cancer.
| S-EPMC6175546 | biostudies-literature
Project description:Because selected xenobiotic-metabolizing enzymes process pro-carcinogens that could initiate ovarian carcinogenesis, we hypothesized that single nucleotide polymorphisms (SNPs) in the genes encoding xenobiotic-metabolizing enzymes are associated with risk of ovarian cancer. Cases with invasive epithelial ovarian cancer (N?=?1571 including 956 of serous sub-type) and controls (N?=?2046) from three studies were genotyped at 11 SNPs in EPHX1, ADH4, ADH1A, NQO2, NAT2, GSTP1, CYP1A1, and NQO1, following an initial SNP screen in a subset of participants. Logistic regression analysis of genotypes obtained via Illumina GoldenGate and Sequenom iPlex technologies revealed the following age- and study-adjusted associations: EPHX1 rs1051740 with increased serous ovarian cancer risk [per-allele odds ratio (OR) 1.17, 95% confidence interval (95% CI) 1.04-1.32, P?=?0.01), ADH4 r1042364 with decreased ovarian cancer risk (OR 0.90, 95% CI: 0.81-1.00, P?=?0.05), and NQO1 rs291766 with increased ovarian cancer risk (OR 1.11, 95% CI: 1.00-1.23, P?=?0.04). These findings are consistent with prior studies implicating these genes in carcinogenesis and suggest that this collection of variants is worthy of follow-up in additional studies.
| S-EPMC3115705 | biostudies-literature
Project description:BackgroundThe association between circulating cholesterol and triglyceride levels and ovarian cancer risk remains unclear.MethodsWe prospectively evaluated the association between cholesterol [total, low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C)] and triglycerides and ovarian cancer incidence in a case-control study nested in the Nurses' Health Study (NHS) and NHSII cohorts and a longitudinal analysis in the UK Biobank.ResultsA total of 290 epithelial ovarian cancer cases in the NHS/NHSII and 551 cases in UK Biobank were diagnosed after blood collection. We observed a reduced ovarian cancer risk comparing the top to bottom quartile of total cholesterol [meta-analysis relative risk (95% confidence interval): 0.81 (0.65-1.01), P trend 0.06], with no heterogeneity across studies (P heterogeneity = 0.74). Overall, no clear patterns were observed for HDL-C, LDL-C, or triglycerides and ovarian cancer risk. Comparing triglyceride levels at clinically relevant cut-off points (>200 vs. ≤200 mg/dL) for cases diagnosed more than 2 years after blood draw saw a positive relationship with risk [1.57 (1.03-2.42); P heterogeneity = 0.003]. Results were similar by serous/non-serous histotype, menopausal status/hormone use, and body mass index.ConclusionsData from two large cohorts in the United States and United Kingdom suggest that total cholesterol levels may be inversely associated with ovarian cancer risk, while triglycerides may be positively associated with risk when assessed at least 2 years before diagnosis, albeit both associations were modest.ImpactThis analysis of two large prospective studies suggests that circulating lipid levels are not strongly associated with ovarian cancer risk. The positive triglyceride-ovarian cancer association warrants further evaluation.
| S-EPMC8568658 | biostudies-literature
Project description:We evaluated whether hair products, which may contain carcinogens and endocrine disruptors that can be absorbed into the bloodstream, are related to ovarian cancer incidence in a prospective cohort. After excluding women with a history of ovarian cancer or bilateral oophorectomy, 40 559 Sister Study participants ages 35-74 at enrollment (2003-2009) were included. Participants completed questionnaires on hair product use, including hair dyes, straighteners/relaxers and permanents/body waves, in the past 12 months. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between hair products and incident ovarian cancer. We assessed associations stratified by tumor type (serous, non-serous). Over a mean follow-up of 10 years, 241 women were diagnosed with ovarian cancer. Ever use of any of the examined hair products during the past year was not associated with ovarian cancer risk. However, frequent use (>4 times/year) of straighteners/relaxers or pressing products in the past year was associated with an increased risk of ovarian cancer (HR = 2.19, 95% CI: 1.12-4.27). Ever use of permanent hair dye was positively associated with non-serous (HR = 1.94, 95% CI 1.12-3.37), but inversely associated with serous (HR = 0.65, 95% CI: 0.43-0.99) tumors (p-for-heterogeneity = 0.002). Our novel findings suggest that frequent use of hair straighteners/relaxers or pressing products, which are primarily used by African American/Black women, and possibly permanent hair dye, may be associated with the occurrence of ovarian cancers.
| S-EPMC8561257 | biostudies-literature
Project description:BackgroundRecent years have witnessed the discovery of similar gene variations between breast cancer and ovarian cancer, inherited breast and ovarian cancer in particular. A large number of case-control studies have been conducted to explore the association of Methylenetetrahydrofolate Reductase (MTHFR) A1298C polymorphism with breast cancer and/or ovarian cancer risk. However, the results are still inconsistent and inconclusive. Consequently, we performed a meta-analysis to evaluate the association between MTHFR A1298C polymorphism and breast, ovarian cancer risk.Materials and methodsA comprehensive retrieval was conducted in the electronic database of PubMed, Web of Science and Chinese National Knowledge Infrastructure (CNKI) until June 2015 to identify eligible studies. A total of 35 studies which examined the association of MTHFR A1298C polymorphism with breast cancer and/or ovarian cancer were identified. The pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the effect of gene polymorphism. And allele model, homozygous model, co-dominant model, dominant model, recessive model were applied.ResultIn the overall analysis, significantly increased breast cancer and/or ovarian cancer risk was found (for allele model A VS C OR = 1.05, CI: 1.02-1.08, P = 4χ10-3; for homozygous model AA VS CC OR = 1.11, CI: 1.03-1.19, P = 5χ10-3; for recessive model (AC +AA) VS CC: OR = 1.10, CI: 1.03-1.18, P = 7χ10-3).ConclusionIn the subgroup analysis, significantly increased breast cancer risk was identified among Caucasians. MTHFR A1298C polymorphism might contribute to an increased risk of breast cancer and/or ovarian cancer susceptibility. In addition, MTHFR A1298C polymorphism had a significant association with breast cancer in Caucasians.
| S-EPMC5416649 | biostudies-literature
Project description:ObjectiveWe have previously shown that TCEAL7 (transcription elongation factor A (SII)-like 7) is epigenetically down-regulated in the majority of epithelial ovarian cancers. We now examine the hypothesis that inherited alterations in TCEAL7 play a role in the etiology of ovarian cancer.MethodsA two-site case-control study of 930 cases of ovarian cancer and 1037 controls, frequency-matched on residence, age and race, was conducted. Six informative SNPs (tagSNPs and putative-functional SNPs) were genotyped. Logistic regression was used to adjust for potential confounders and determine if inherited variation at this locus was associated with risk of ovarian cancer in general and among cases with invasive disease and serous histology. Gene-level principal component and haplotype analyses were also conducted.ResultsNone of the SNPs or haplotypes studied were significantly associated with ovarian cancer risk overall. However, among the 440 invasive serous cases, the minor alleles for three correlated SNPs were significantly associated with reduced risk (p-values<0.05), summarized gene-level variation was weakly associated with reduced risk (p-value=0.05), and the predominant haplotype was less common among cases than controls (0.36 v 0.40, p-value=0.05), consistent with single-SNP results.ConclusionTCEAL7 polymorphisms may play a role in the development of invasive serous ovarian cancers. Follow-up molecular and replication studies are warranted.
| S-EPMC2758312 | biostudies-literature