MTHFR polymorphisms, dietary folate intake and breast cancer risk in Chinese women

Division of Epidemiology, Jiangsu Province Institute of Cancer Research, Nanjing, China.
Journal of Human Genetics (Impact Factor: 2.46). 07/2009; 54(7):414-8. DOI: 10.1038/jhg.2009.57
Source: PubMed


To evaluate the relationship between dietary folate intake and genetic polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) with reference to breast cancer risk, we conducted a case-control study with 669 cases and 682 population-based controls in the Jiangsu Province of China. MTHFR C677T and A1298C genotypes were identified using PCR-RFLP (restrictrion fragment length polymorphism) methods. Dietary folate intake was assessed using an 83-item food frequency questionnaire. Odds ratios (ORs) were estimated with an unconditional logistic model. The frequencies of MTHFR C677T C/C, C/T and T/T genotypes were 32.37, 48.88 and 18.75% in cases and 37.66, 48.24 and 14.10% in controls, respectively. The difference in distribution was significant (chi(2)=6.616, P=0.037), the T/T genotype being associated with an elevated OR (adjusted for age, menopausal status, body mass index (BMI), income, work intensity and status of smoking and drinking) for breast cancer (1.62, 95% confidence interval (95% CI): 1.14-2.30). The frequencies of MTHFR A1298C A/A, A/C and C/C were 71.47, 27.08 and 1.44% in cases and 68.11, 30.13 and 1.76% in controls, respectively, with no significant differences being found (chi(2)=1.716, P=0.424). A significant inverse relationship was observed between folate intake and breast cancer risk. Compared with the lowest tertile of folate intake, the adjusted OR for breast cancer in the top tertile was 0.70 (95% CI: 0.53-0.92). However, no significant interaction was observed between folate intake and the MTHFR C677T polymorphism. Among individuals with the MTHFR A1298C A/A genotype, adjusted ORs for breast cancer were 0.89 (0.62-1.27) and 1.69 (1.20-2.36) for the second to the third tertile of folate intake compared with the highest folate intake group (tread test, P=0.0008). The findings of this study suggest that MTHFR genetic polymorphisms and dietary intake of folate may modify susceptibility to breast cancer.

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Available from: Kazuo Tajima, May 12, 2015
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    • "After discarding five duplicate publications [67] [68] [69] [70] [71] , 51 articles covering 17 provinces of China were finally included in this systematic review, including 3 cohort studies [35] [42] [54] and 48 case-control studies. There were 21 articles focusing on active smoking only, 19 articles on passive smoking only, and 11 articles on both active and passive smoking (Table 1). "
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    ABSTRACT: Previous studies suggested that smoking and passive smoking could increase the risk of breast cancer, but the results were inconsistent, especially for Chinese females. Thus, we systematically searched cohort and case-control studies investigating the associations of active and passive smoking with breast cancer risk among Chinese females in four English databases (Pubmed, Embase, ScienceDirect, and Wiley) and three Chinese databases (CNKI, WanFang, and VIP). Fifty-one articles (3 cohort studies and 48 case-control studies) covering 17 provinces of China were finally included in this systematic review. Among Chinese females, there was significant association between passive smoking and this risk of breast cancer [odds ratio (OR): 1.62, 95% confidence interval (CI): 1.39-1.85; I2 = 75.8%, P < 0.001; n = 26] but no significant association between active smoking and the risk of breast cancer (OR: 1.04, 95% CI: 0.89-1.20; I2 = 13.9%, P = 0.248; n = 31). The OR of exposure to husband's smoking and to smoke in the workplace was 1.27 (95% CI: 1.07-1.50) and 1.66 (95% CI: 1.07-2.59), respectively. The OR of light and heavy passive smoking was 1.11 and 1.41, respectively, for women exposed to their husband's smoke (< 20 and ≥ 20 cigarettes per day), and 1.07 and 1.87, respectively, for those exposed to smoke in the workplace (<300 and ≥300 min of exposure per day). These results imply that passive smoking is associated with an increased risk of breast cancer, and the risk seems to increase as the level of passive exposure to smoke increases among Chinese females. Women with passive exposure to smoke in the workplace have a higher risk of breast cancer than those exposed to their husband's smoking.
    Ai zheng = Aizheng = Chinese journal of cancer 05/2014; 33(6). DOI:10.5732/cjc.013.10248 · 2.16 Impact Factor
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    • "Serine hydroxymethyltransferase (SHMT), methionine synthase (MS), methionine synthase reductase (MTRR) and cystathionine beta synthase (CBS) are genes that encode enzymes involved in the folate and Hcy metabolic pathway, which are critical in the DNA synthesis, methylation process and Hcy metabolism (Figure 1) [26]. Studies have suggested that polymorphisms in these genes may be related to plasma Hcy levels increasing and cancer development [27-29], but the study on interaction between plasma Hcy levels, above-mentioned genetic polymorphisms in folate pathway and breast Cancer susceptibility is still lacking. Thus the aim of this study was to analyze the possible associations between Hcy concentration in serum, polymorphisms of enzymes involved in folate/methionine metabolism and breast cancer susceptibility. "
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    ABSTRACT: Folate plays a pivotal role in DNA synthesis, repair, methylation and homocysteine (Hcy) metabolism. Therefore, alterations in the folate-mediated one-carbon metabolism may lead to abnormal methylation proliferation, increases of tumor/neoplasia and vein thrombosis/cardiovascular risk. The serine hydroxymethyhransferase (SHMT), methionine synthase (MS), methionine synthase reductase (MTRR) and cystathionine beta synthase (CBS) regulate key reactions in the folate and Hcy metabolism. Therefore, we investigated whether the genetic variants of the SHMT, MS, MTRR and CBS gene can affect plasma Hcy levels and are associated with breast cancer risk. Genotyping was performed by PCR-RFLP method. Plasma Hcy levels were measured by the fluorescence polarization immunoassay on samples of 96 cases and 85 controls. (a) The SHMT 1420 T, MS 2756G, MTRR 66G allele frequency distribution showed significant difference between case and controls (p < 0.01 ~ 0.05). (b) The concentration of plasma Hcy levels of SHMT 1420TT was significantly lower than that of the wild type, while the plasma Hcy levels of MS 2756GG, CBS 699TT/1080TT significantly higher than that of the wild type both in case and controls. The plasma Hcy levels of MTRR 66GG was significantly higher than that of wild type in cases. The plasma Hcy levels of the same genotype in cases were significantly higher than those of controls except SHMT 1420CC, MS 2756AA, MTRR 66GG; (c) Multivariate Logistic regression analysis showed that SHMT C1420T (OR = 0.527, 95% CI = 0.55 ~ 1.24), MS A2756G (OR = 2.32, 95% CI = 0.29 ~ 0.82), MTRR A66G (OR = 1.84, 95% CI = 0.25 ~ 1.66) polymorphism is significantly associated with breast cancer risk. And elevated plasma Hcy levels were significantly linked to increased risk of breast cancer (adjusted OR = 4.45, 95% CI = 1.89-6.24 for the highest tertile as compared with the lowest tertile). The current study results seem to suggest a possibility that SHMT C1420T mutation may be negatively correlated with breast cancer susceptibility; while MS A2756G and MTRR A66G mutation may be positively associated with breast cancer risk. SHMT C1420T, MS A2756G, MTRR A66G, CBS C1080T, CBS C699T locus mutation may be factors affecting plasma levels of Hcy. The plasma Hcy levels could be metabolic risk factor for breast cancer risk to a certain extent.
    Hereditary Cancer in Clinical Practice 02/2014; 12(1):2. DOI:10.1186/1897-4287-12-2 · 1.47 Impact Factor
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    • "There were only 6 (2.21%) and 8 (4.49%) postmenopausal women, respectively, in the group of the TT genotype. However the distribution of the TT genotype in normal Chinese and Iranian women was 14.10% and 6.4% in other researches [38] [39] . However , there was no statistically significant difference of BMD in the lumbar spine between the TT and CC/ CT genotype. "
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    ABSTRACT: Osteoporosis is a condition characterized by low bone mineral density (BMD) and micro-architectural changes in the bone tissue. The risk of osteoporosis is partly determined by genetic factors. The role of C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene has been investigated in postmenopausal osteoporosis. However, the relationship between MTHFR polymorphism and BMD is still controversial. We carried out a meta-analysis of 5,833 subjects to evaluate the association of MTHFR and BMD in postmenopausal women. Databases of MEDLINE, Web of Science, Scopus and CNKI were retrieved for all publications relating to MTHFR polymorphism and BMD in postmenopausal women. Five eligible studies were selected for meta-analysis. All these articles studied the association of MTHFR polymorphism and BMD of the femoral neck and lumbar spine in postmenopausal women. Our analysis suggested that postmenopausal women with the TT genotype had lower femoral neck BMD than the women with the CC/CT genotype, and the weighted mean difference (WMD) was -0.01 g/cm(2) [95% confidence interval (CI): (-0.01, -0.01), P < 0.01]. However, BMD of the lumbar spine of postmenopausal women with the TT genotype was not significantly different from that of women with the CC/CT genotype. In the random effects model, the WMD between the TT and TC/CC genotype was -0.01 g/cm(2) [95% CI: (-0.04, 0.01), P = 0.32]. The C677T polymorphism of the MTHFR gene is associated with BMD of the femoral neck in postmenopausal women. Women with the TT genotype of the MTHFR gene have lower BMD, suggesting that the TT genotype may be a risk factor for postmenopausal osteoporosis.
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