Thymidylate synthase and methylenetetrahydrofolate reductase polymorhisms and breast cancer susceptibility in a Brazilian population

Abstract

Breast cancer (BC) is the most diagnosed cancer and the leading cause of cancer death in women worldwide. Polymorphisms in genes involved in the folate pathway are suggested as possible BC etiological factors. Among them, Thymidylate synthase (TYMS) has two polymorphisms related to BC: TSER and 1494del6. Methylenetetrahydrofolate reductase (MTHFR) has two SNPs, C677T and A1298C, that also could increase breast cancer risk.This work aimed to determine if TYMS and MTHFR genes polymorphisms are related to BC risk in a population ofNorth Brazil. A total of 124 DNA samples, obtained from BC patients and control women, were genotyped utilizing PCR and automatic sequencing. Chi-square, G-test, Fisher’s exact test, and odds ratio were applied toanalyse the data. Significant associations with BC risk were observed for TYMS 3R allele carriers. Besides, patients with the − 6 allele of 1494del6 polymorphism were more likely to develop aggressive BC molecular tumortypes (Luminal B, HER2-positive, and Triple-Negative). In conclusion, TYMS polymorphisms are related to BCrisk in the studied population, as the 3R allele is associated with BC susceptibility and the presence of the1494del6–6 allele increases the development risk of more aggressive BC subtypes. Those findings may be useful for predicting the efficacy of anti-TS drugs in BC patients.