Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.5.7.1 (methylenetetrahydrofolate reductase)
 2,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe here a case-control study to identify associations between polymorphisms at the methylenetetrahydrofolate reductase (MTHFR) and cytochrome P-450 1A1 (CYP1A1) genes and susceptibility to endometrial cancer. Accordingly, genotype frequencies in 80 endometrial carcinoma patients were compared with frequencies in 60 controls. DNA analysis suggest a significantly increased endometrial cancer risk with an alanine to valine substitution at nucleotide 677 of MTHFR gene with an odds ratio of 2.8 (95% confidence interval: 1.36-6.14, P = 0.002). Moreover, the tumors from patients with the valine allele were more undifferentiated (P = 0.03). On the other hand, a recently described mutation in exon 7 of CYP1A1 gene (threonine exchanged to asparagine in codon 461) showed a strong association with endometrial cancer risk with an odds ratio of 6.36 (95% confidence interval: 1.99-26.5, P = 0.0004). Thus, this study suggests that polymorphisms at MTHFR and a novel CYP1A1 variant could influence susceptibility to endometrial cancer, although larger sample sizes would be required to corroborate these findings.
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PMID:Germ line polymorphisms in cytochrome-P450 1A1 (C4887 CYP1A1) and methylenetetrahydrofolate reductase (MTHFR) genes and endometrial cancer susceptibility. 945 Apr 74

Serious and endometrioid carcinomas differ dramatically in their clinical behavior; however, the specific significance of villoglandular (papillary) differentiation in endometrioid carcinoma has been studied rarely. We compared the clinicopathologic features and genetic alterations in 28 villoglandular endometrioid carcinomas compared with 60 nonvilloglandular endometrioid carcinomas and 60 healthy women. The study revealed a slight increase in the frequency of early-stage disease in villoglandular tumors compared with nonvilloglandular tumors. No differences were observed in the age at onset or cellular grade. The oncogene and susceptibility gene analyses revealed a positive association of K-ras oncogene mutation and germline variants of the cytochrome P-450 1A1 (CYP1A1) gene and an inverse association of the p53PIN3 variant with villoglandular carcinomas, whereas no differences were observed in the c-erbB2/neu oncogene amplification or the methylenetetrahydrofolate reductase germline variant. Finally, a positive association was found between CYP1A1 and methylenetetrahydrofolate reductase variants and the presence of papillary differentiation in the myometrial component. The results suggest that the villoglandular differentiation pattern arises without aggressive clinicopathologic features in a genetic background of transforming and carcinogen-metabolism genes, characteristic of estrogen-related endometrial tumors (type 1) not exhibiting an unfavorable prognosis.
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PMID:Clinicopathologic features and genetic alterations in endometrioid carcinoma of the uterus with villoglandular differentiation. 1007 8

Endometrial polyps and endometrial neoplasms are a recognized complication of chronic tamoxifen treatment. This study describes an endometrial carcinoma that developed in a woman receiving low-dose tamoxifen treatment for breast cancer. Little is known about steroid receptor status, somatic alterations in oncogenes and tumor suppressor genes, and inherited susceptibility in endometrial carcinomas associated with tamoxifen use. In the present case, the endometrial carcinoma was negative for estrogen receptors and weakly positive for progesterone receptors. In addition, analysis of K-ras, c-erbB2/neu, cyclin D1, and p53 status revealed a codon 12 point mutation in the K-ras oncogene. The patient was determined not to be a carrier of germ-line mutations in cytochrome P-450 1A1 (CYP1A1), an estrogen-metabolizing gene previously associated with enhanced endometrial cancer risk, but she was a carrier of a methylenetetrahydrofolate reductase gene variant related with putative alterations in DNA methylation.
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PMID:Endometrial carcinoma in tamoxifen-treated breast cancer patient: clinicopathological, immunohistochemical, and genetic analysis. 1054 49

Polymorphisms in genes can lead to differences in the level of susceptibility of individuals to potentially adverse effects of environmental influences, such as chemical exposure, on prenatal development or male or female reproductive function. We have reviewed the literature in this area, with the caveat that papers involving straight gene knock-outs in experimental animals, without a clear human relevance, were largely excluded. This review represents current knowledge in this rapidly moving field, presenting both human epidemiological and animal data, where available. Among the polymorphic genes and environmental interactions discussed with respect to prenatal development are those for P-glycoprotein (multidrug resistance protein) and the avermectins; methylenetetrahydrofolate reductase (MTHFR), an enzyme in folate metabolism, and dietary folic acid; transforming growth factor alpha (TGFalpha) and cigarette smoke; and alcohol dehydrogenase (ADH) and cytochrome P-450 (CYP) 2E1 in association with alcohol consumption. Effects on male reproduction attributable to gene-environment interaction involve infertility seen as a result of either organophosphorous (OP) pesticide interaction with the polymorphic paraoxonase (PON1) gene or antiandrogenic agent interaction with the androgen receptor (AR). MTHFR, folate metabolism, and dietary folic acid are also considered in conjunction with preeclampsia and early pregnancy loss, and the effect of the interaction of glutathione S-transferase (GST) with exposure to benzene or cigarette smoke on pregnancy maintenance is explored. As a conclusion, we offer a discussion of lessons learned and suggested research needs.
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PMID:Gene-environment interactions: a review of effects on reproduction and development. 1560 83