Abstract

Objective: we conducted a case-control study to investigate the association between dietary folate, vitamin B6 and vitamin B12 intake, MTHFR and MTR genotype, and breast cancer risk. Methods: Genotyping for MTHFR C677T and A1298C and MTR A2756G polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) method. The intake of folate, vitamin B6 and vitamin B12 were calculated by each food item from questionnaire. Results: Subjects with breast cancer tended to have more first-degree relatives (χ2=30.77, P<0.001) and have high intake of folate (t=2.42, P=0.008) and Vitamin B6 (t=2.94, P=0.002). Compared to the reference group, women with MTHFR 677 TT genotype and T allele had a significantly increased risk of breast cancer, with ORs (95%CI) of 1.8(1.08-2.27) and 1.39(1.02-1.92), respectively. For those who had folate intake<450 ug/day, MTHFR 667TT genotype was associated with a higher risk of breast cancer (OR=2.45, 95% CI=1.09-5.82, P=0.02). Similarly, subjects with Vitamin B6 intake<0.84 mg/day and MTHFR 667T allele genotype was correlated with a marginally increased risk of breast cancer. A significant interaction was observed between MTHFR C667T polymorphism and folate intake on the risk of breast cancer (P for interaction was 0.025). Conclusion: This case-control study found a significant association between MTHFR C667T polymorphism, folate intake and vitamin B6 and breast cancer risk, and a significant interaction was observed between MTHFR C667T polymorphism and folate intake on the risk of breast cancer.

Highlights

  • Breast cancer is the most common malignancy in women worldwide, and it has become the second leading cause of death in Chinese females.[1]

  • B vitamins could induce defective DNA repair and chronmosomal fragile site expression, and cause chromosomal breaks and micronucleus formation.[5]. These functions could play an important role in the development of various cancers. 6-10 The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) irreversibly catalyzes the conversion of 5,10-methylenetetrahydrofolate (5,10-methylene THF) to 5-methyltetrahydrofolate (5-methyl THF), play an important role in folate metabolism, and the polymorphisms in folate-metabolizing genes may influence the function of synthesis in DNA repair.[11]

  • We found high intake of folate and Vitamin B6 was associated with a significantly increased risk of breast cancer, and MTHFR 677TT genotype was correlated with increased risk of breast cancer

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Summary

Introduction

Breast cancer is the most common malignancy in women worldwide, and it has become the second leading cause of death in Chinese females.[1]. Folate and other methyl-related B vitamins are necessary for DNA synthesis, integrity and stability.[4] Deficiency of folate and methyl-related. B vitamins could induce defective DNA repair and chronmosomal fragile site expression, and cause chromosomal breaks and micronucleus formation.[5] These functions could play an important role in the development of various cancers. 6-10 The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) irreversibly catalyzes the conversion of 5,10-methylenetetrahydrofolate (5,10-methylene THF) to 5-methyltetrahydrofolate (5-methyl THF), play an important role in folate metabolism, and the polymorphisms in folate-metabolizing genes may influence the function of synthesis in DNA repair.[11] Two common genetic polymorphisms in MTHFR (C677T and A1298C) and one in Methionine synthase (MTR) (MTR A2756G) were widely studies, and found the genetic variations of MTHFR and MTR are associated with increased or reduced risk of breast cancer.[4,12,13,14,15]

Objectives
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Conclusion

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