Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Endometrial carcinoma in tamoxifen-treated breast cancer patient: clinicopathological, immunohistochemical, and genetic analysis. 1054 49

The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with reduced enzyme activity, hyperhomocysteinaemia and increased risk for atherosclerosis in homozygotes. We examined the frequency of this mutation and its association with disease pattern in 491 Jewish women with either sporadic (n = 355; 72%) or hereditary (n = 136; 28%) breast and/or ovarian cancer and in 69 asymptomatic BRCA1/2 mutation carriers, genotyped for the three predominant Jewish founder BRCA1/2 mutations (185delAG, 5382insC and 6174delT). 677T homozygotes were equally distributed among women with sporadic breast and/or ovarian cancer (71/355; 20.0%) and among BRCA1/2 mutation carriers (43/205; 21.0%) (P=non-significant). 677T homozygotes were equally distributed among women diagnosed with breast cancer prior to (22/122; 18.0%) and after 42 years of age (42/243; 17.3%). Among BRCA1/2 carriers, the rate of 677T homozygotes in manifesting cancer (32/136; 23.5%) and asymptomatic individuals (11/69; 15.9%) was not significantly different. The rate of 677T homozygotes (24/72; 33.3%) was higher (P=0.0026) among women with bilateral breast cancer and those with both breast and ovarian carcinoma than among those with unilateral breast cancer (64/365; 17.5%). Differences in morbidity (one versus multiple breast/ovarian tumours) are mainly attributed to 677T homozygosity and partly to BRCA1/2 mutations. Confirmation of these data, namely, that the 677T allele is significantly more common in cases of bilateral breast cancer or combined breast and ovarian cancer would have important clinical implications.
 ...
PMID:Association of the C677T polymorphism in the MTHFR gene with breast and/or ovarian cancer risk in Jewish women. 1109 4

Evidence is growing that low folate status may be a factor in the aetiology of several cancers, including breast cancer. The methylenetetrahydrofolate reductase gene (MTHFR), which has a key role in folate metabolism, is polymorphic. We report a case-control study of two functional polymorphisms in MTHFR, dietary folate intake and breast cancer. Sixty-two cases with invasive breast cancer and sixty-six general practice controls participated. Women reporting the highest dietary folate intake had non-significantly reduced breast cancer risk (odds ratio (OR) = 0.49, 95% confidence interval (CI) 0.20-1.20). Risk was significantly lower for the 1298CC genotype compared to AA (OR = 0.24, 95% CI 0.06-0.97). Relative to compound wild-type subjects, compound heterozygotes had moderately reduced risk (OR = 0.47, 95% CI 0.11-1.92) and homozygote variants (677TT and/or 1298CC) greater reduced risk (OR = 0.26, 95% CI 0.07-0.96); the trend was statistically significant. Patterns in risk with regard to genotype and folate combinations are broadly similar those reported for colorectal neoplasia. The roles of MTHFR and folate in breast cancer aetiology are likely to be complex.
 ...
PMID:Folate and breast cancer: the role of polymorphisms in methylenetetrahydrofolate reductase (MTHFR). 1243 Jan 80

Colorectal cancer and adenoma risk are inversely associated with higher total folate intake. Significant modifiers of cancer risk also include other methyl-related nutrients and alcohol. Adequate folate intake is particularly important for women at higher risk for breast cancer because of moderate alcohol consumption. The methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism is associated with a reduced risk of some forms of cancer. The protective effect of this folate-related polymorphism is dependent on adequate folate status. Cancer risk may be increased in individuals with the homozygous genotype for the MTHFR 677C-->T polymorphism who have low status of methyl-related nutrients including folate. Intake recommendations to potentially reduce cancer risk include substitution of low folate foods with folate-dense fruits and vegetables and in countries where there is no mandatory folic acid fortification, increased consumption of folic acid from available fortified foods or supplements. Adequate dietary intake of vitamin B-6 and methionine can be achieved by consumption of low fat, concentrated food sources of these nutrients. The recommended intake for vitamin B-12 for individuals >/==" BORDER="0">51 y should be provided predominately in crystalline form (e.g., fortified ready-to-eat cereal, supplements). If alcohol is consumed, consumption should be restricted to <15 g/d or <1 drink/d. The negative effects of low intakes of the methyl-related nutrients with high intakes of alcohol are additive, therefore changes in overall dietary patterns to ensure the consumption of a protective high methyl diet are recommended.
 ...
PMID:Folate, methyl-related nutrients, alcohol, and the MTHFR 677C-->T polymorphism affect cancer risk: intake recommendations. 1460 9

Folate plays an important role in DNA methylation, synthesis, and repair; intake has been associated with breast cancer. The folate-metabolizing enzyme, methylenetetrahydrofolate reductase (MTHFR) is polymorphic at nucleotides 677 (C-->T) and 1298 (A-->C), resulting in allozymes with decreased activity. We evaluated these two common polymorphisms and their effects on the folate intake and breast cancer risk association in a population-based case-control study of 1144 breast cancer cases and 1236 controls using a PCR-RFLP-based assay. All subjects completed in-person interviews, which included a food frequency questionnaire. Unconditional logistic regression models were used to calculate odds ratios and their 95% confidence intervals, after adjusting for potential confounding factors. Cases and controls were similar in the distribution of MTHFR polymorphisms at codons 677 (41.4% cases and 41.8% controls carried the T allele) and 1298 (17.6% cases and 17.5% controls carried the C allele). An inverse association of breast cancer risk with folate intake was observed in all genotype groups, particularly among subjects with the 677TT genotype. Compared with those with the 677CC genotype and high folate, the adjusted odds ratios (95% confidence intervals) associated with low folate intake were 1.94 (1.15-3.26), 2.17 (1.34-3.51), and 2.51 (1.37-4.60) for subjects who had CC, CT, and TT genotypes (p for interaction, 0.05). No modifying effect of A1298C genotypes on the association of folate intake with breast cancer risk was observed. Results of this study suggest that the MTHFR C677T polymorphisms may modify the association between dietary folate intake and breast cancer risk.
 ...
PMID:MTHFR polymorphisms, dietary folate intake, and breast cancer risk: results from the Shanghai Breast Cancer Study. 1497 91

The methylenetetrahydrofolate reductase (MTHFR) gene is a polymorphic gene involved in folate metabolism, DNA biosynthesis, methylation and genomic integrity in actively dividing cells. The MTHFR C677T and A1298C polymorphisms are likely to play an important role in the susceptibility to breast cancer. In this case-control study, we examined the role of MTHFR C677T and A1298C polymorphisms in breast cancer patients. We genotyped 118 premenopausal women with sporadic breast cancer and 193 controls, using a PCR-RFLP method. The allele frequencies of the MTHFR 677T were 31.36% in the breast cancer cases and 28.76% in the controls. The allele frequencies of the MTHFR 1298C were 37.29% in the breast cancer subjects and 31.35% in the controls. Frequencies of MTHFR C677C, C677T and T677T were 50.8, 33.9 and 14.4% in the breast cancer patients and 48.7, 45.1 and 6.2% in the controls, respectively. The results of a chi(2) analysis indicated that the MTHFR 677T allele was significantly distributed (chi(2) = 7.234; p = 0.027). Likewise, the MTHFR T677T genotype showed a 2.5-fold increased risk for breast cancer and the C1298C genotype showed a 1.9-fold increased risk for breast cancer. In the compound genotypes, T677T/A1298A and C677C/C1298C showed a 4.472- and a 2.301-fold increased risk for breast cancer (OR = 4.472, p = 0.001, and OR = 2.301, p = 0.024), respectively. In conclusion, our data suggest that the MTHFR 677T, 1298C alleles, T677T, C1298C genotypes, and C677C/C1298C and T677T/A1298A compound genotypes are genetic risk factors for premenopausal women with sporadic breast cancer.
 ...
PMID:Polymorphisms in the MTHFR gene are associated with breast cancer. 1500 88

A limited number of genes have been identified that explain heritable risks of breast cancer (BC). We searched for low-penetrant genes in an association study using two populations: 223 Finnish unselected patients and 172 Polish familial cases, both with locally collected healthy controls. Candidate genes included DNA repair genes, methylenetetrahydrofolate reductase (MTHFR) and cyclin D1 genes. The frequencies for single nucleotide polymorphisms (SNPs) were measured in the following genes: NBS1, XPC, XPD, XRCC1, XRCC3, MTHFR, and cyclin D1. Odds ratios (ORs) were calculated to the wild-type genotype. The positive findings in the Finnish series were repeated in the Polish series. Significant findings among Finns were associations to XPC exon 15, XPD exon 10 and XRCC3 exon 7, the latter of borderline significance. None of these results could be repeated in the Polish series. The XPC result among Finns was probably an artifact of the control group deviating from the Hardy-Weinberg Equilibrium (HWE). The attempt to repeat the result for the XPD polymorphism among Poles was probably not valid because the control group deviated from the HWE. We conclude that within statistical power of the present study, none of the tested polymorphisms associated with BC, with the probable exception of XPD.
 ...
PMID:Single nucleotide polymorphisms in breast cancer. 1501 Aug 95

Breast cancer risk may be associated with folate status or the C677T genotype of the methylenetetrahydrofolate reductase (MTHFR) gene. We compared serum folate concentrations and C677T genotype in 141 breast cancer patients and 109 age-matched controls. Serum folate was significantly lower in cases compared to controls (geometric means, 5.7 versus 6.6 microg/l; P=0.005). Breast cancer risk was not associated with C677T genotype. After adjusting for age of menarche, parity, alcohol intake and total fat intake we observed reductions in odds ratios for breast cancer risk comparing the highest with the lowest quartiles of serum folate concentrations of 0.23 (95% confidence interval (CI) 0.09, 0.54) for the entire group, 0.27 (CI 0.09, 0.80) for the wild-type and 0.08 (CI 0.01, 0.52) for the heterozygous C677T genotype. We conclude that for the whole group, and the wild-type and heterozygous C677T genotypes, increased serum concentrations of folate were associated with reduced risks of breast cancer.
 ...
PMID:Reduced breast cancer risk with increasing serum folate in a case-control study of the C677T genotype of the methylenetetrahydrofolate reductase gene. 1511 Aug 90

To evaluate the interactive effect of methylenetetrahydrofolate reductase (MTHFR) genotype and dietary factors on the development of breast cancer, a hospital based case-control study was conducted in South Korean study population consisting of 189 histologically confirmed incident breast cancer cases and their 189 age-matched controls without present or previous history of cancer. A PCR-RFLP method was used for the genotyping of MTHFR (C677T) and statistical evaluations were performed by unconditional logistic regression analysis. Consumption of some dietary factors, such as green vegetables (OR = 0.3, 95% CI: 0.2-0.6), white vegetables (OR = 0.3, 95% CI: 0.1-0.7) mushrooms (OR = 0.4, 95% CI: 0.3-0.7), and meats (OR = 1.7, 95% CI: 1.1-2.8) significantly decreased or increased the risk of breast cancer. Although the breast cancer risk was 1.7-fold (95% CI: 0.8-3.2) increased in women with MTHFR TT genotype, the association was not statistically significant. Women with MTHFR TT genotype and low green vegetable intake increased 5.6-fold (95% CI: 1.2-26.3) risk of breast cancer compared to high green vegetable intake group containing MTHFR CC/CT genotype. However, the interaction was not significant (p for interaction = 0.96). Our findings suggest that MTHFR polymorphism did not influence individual susceptibility to breast cancer. However MTHFR (C667T) genotype and green vegetable intakes appeared to have the interactive effect in breast cancer development.
 ...
PMID:Methylenetetrahydrofolate reductase polymorphism, diet, and breast cancer in Korean women. 1515 Apr 39

Accumulating evidence from epidemiologic studies suggests that risk of breast cancer is reduced in relation to increased consumption of folate and related B vitamins. We investigated independent and joint effects of B vitamin intake as well as two polymorphisms of a key one-carbon metabolizing gene [i.e., methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C] on breast cancer risk. The study uses the resources of a population-based case-control study, which includes 1,481 cases and 1,518 controls. Significant inverse associations between B vitamin intake and breast cancer risk were observed among non-supplement users. The greatest reduction in breast cancer risk was observed among non-supplement users in the highest quintile of dietary folate intake [odds ratio (OR), 0.61; 95% confidence interval (95% CI), 0.41-0.93] as compared with non-supplement users in the lowest quintile of dietary folate intake (high-risk individuals). The MTHFR 677T variant allele was associated with increased risk of breast cancer (P, trend = 0.03) with a multivariate-adjusted OR of 1.37 (95% CI, 1.06-1.78) for the 677TT genotype. The 1298C variant allele was inversely associated with breast cancer risk (P, trend = 0.03), and was likely due to the linkage of this allele to the low-risk allele of 677C. The MTHFR-breast cancer associations were more prominent among women who did not use multivitamin supplements. Compared with 677CC individuals with high folate intake, elevation of breast cancer risk was most pronounced among 677TT women who consumed the lowest levels of dietary folate (OR, 1.83; 95% CI, 1.13-2.96) or total folate intake (OR, 1.71; 95% CI, 1.08-2.71). From a public heath perspective, it is important to identify risk factors, such as low B vitamin consumption, that may guide an effective prevention strategy against the disease.
 ...
PMID:One-carbon metabolism, MTHFR polymorphisms, and risk of breast cancer. 1573 51


1 2 3 4 5 6 Next >>