Abstract
We investigated the association between methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthetase (MTR A2756G), and methionine synthase reductase (MTRR A66G) polymorphisms involved in folate pathway and breast cancer risk, and the interaction between these polymorphisms and tobacco and alcohol consumption. Furthermore, we evaluated the association between these polymorphisms and clinicopathological variables. This case-control study included 606 Brazilian women, comprising 128 patients with breast cancer and 478 controls. MTHFR and MTR polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and MTRR polymorphisms using real-time PCR. Age ≥50 years (odds ratio [OR]: 2.65; 95% confidence interval [CI]: 1.65-4.26; p<0.001) and alcohol consumption (OR: 1.76; 95% CI: 1.0-2.85; p=0.021) were associated with an increased risk of breast cancer. For MTHFR A1298C, we observed a reduced risk of developing breast cancer in the codominant model (genotype CC-OR: 0.22; 95% CI: 0.06-0.74; p=0.014), recessive model (OR: 0.22; 95% CI: 0.07-0.76 p=0.004), and log-additive model (OR: 0.70; 95% CI: 0.49-0.98; p=0.035). Women aged ≥50 years and those who are alcohol consumers had increased susceptibility to breast cancer, and MTHFR A1298C modulated the risk for this disease. This is the first study to evaluate the association between polymorphisms in folate metabolism and breast cancer in the northwest region of São Paulo State, Brazil.
Highlights
Breast cancer is the most common cancer and the second most common cause of mortality (INCA, 2019; Siegel et al, 2021)
Regarding single nucleotide polymorphisms (SNPs) and breast cancer subtypes, we did not observe an association between luminal A, luminal B, human epidermal growth factor receptor-type 2 (HER2) overexpression, and triple-negative subtypes and polymorphisms (Table 3)
We observed that the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism reduced the risk of developing breast cancer in the codominant model, recessive model (OR: 0.22; 95% CI: 0.07–0.76; p=0.004), and logadditive model (OR: 0.70; 95% CI: 0.49–0.98; p=0.035)
Summary
Breast cancer is the most common cancer and the second most common cause of mortality (INCA, 2019; Siegel et al, 2021). Factors related to developed countries linked to increased breast cancer cases include early menarche, older age upon first occasion of giving birth, nulliparity, obesity, alcohol consumption, breastfeeding, and physical activity (Key et al, 2001; Arthur et al 2020). Under methionine synthetase (MTR) and methionine synthase reductase (MTRR) enzyme activity, 5-methyltetrahydrofolate is converted to tetrahydrofolate, and the donated methyl group is used in methylation circuits, including the conversion of homocysteine to methionine, and is pivotal to the activity of S-adenosyl-L-methionine (SAM) synthase and DNA methyltransferases (Galbiatti, et al, 2012a; Mentch and Locasale, 2016; Hiraoka and Kagawa, 2017)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
