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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    • "p = 0.052) Fo¡ §rsti 2004 Langsenlehner 2008 Justenhoven 2005 Platek 2009 Xu 2007 Chen 2005 Prasad 2011 Ericson 2009 Mixed Caucasian Batschauer 2011 Langsenlehner 2003 Qi 2004 Alshatwi 2010 Barbosa 2012 Yuan 2009 Sangrajrang 2010 Suzuki 2008 Bentley 2010 Study Deligezer 2005 Subtotal (I-squared = 53.5%, p = 0.003) Subtotal (I-squared = 85.3%, p = 0.000) Kalemi 2005 Lin 2004 Chou 2006 Ergul 2003 Weiner 2010 Gao 2009 Semenza 2003 Lajin 2012 Akram 2012 Cerne 2011 ID Asian Sharp 2002 Naushad 2011 Maruti 2009 Jakubowska 2012 Jin 2009 Inoue 2008 Macis 2007 Henr¡äquez-Herna¡ändez 2009 Kalyankumar 2006 Hekim 2007 Lee 2004 Reljic 2007 Shrubsole 2004 Ma 2009 Ma 2009 Kotsopoulos 2008 Campbell 2002 Grieu 2004 Yu 2007 Li 2009 "
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    ABSTRACT: The association between MHTFR Ala222Val polymorphism and breast cancer (BC) risk are inconclusive. To derive a more precise estimation of the relationship, a systematic review and meta-analysis was performed. A comprehensive search was conducted through researching MEDLINE, EMBASE, PubMed, Web of Science, Chinese Biomedical Literature database (CBM) and China National Knowledge Infrastructure (CNKI) databases before August 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association. A total of 51 studies including 20,907 cases and 23,905 controls were involved in this meta-analysis. Overall, significant associations were found between MTHFR Ala222Val polymorphism and BC risk when all studies pooled into the meta-analysis (Ala/Ala vs Val/Val: OR=0.870, 95%CI=0.789–0.958,P=0.005; Ala/Val vs Val/Val: OR=0.895, 95%CI=0.821–0.976, P=0.012; dominant model: OR=0.882, 95%CI=0.808–0.963, P=0.005; and recessive model: OR = 0.944, 95%CI=0.898–0.993, P=0.026; Ala allele vs Val allele: OR = 0.935, 95%CI=0.887–0.986, P=0.013). In the subgroup analysis by ethnicity, the same results were found in Asian populations, while no significant associations were found for all comparison models in other Ethnicity populations. In conclusion, our meta-analysis provides the evidence that MTHFR Ala222Val gene polymorphisms contributed to the breast cancer development. Virtual slides The virtual slide(s) for this article can be found here:
    Diagnostic Pathology 12/2012; 7(1):171. DOI:10.1186/1746-1596-7-171 · 2.60 Impact Factor
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