Genetic profile and determinants of homocysteine levels in Kazakhstan patients with breast cancer.

To analyze associations between homocysteine level, MTHFR and FTO rs1477196 polymorphisms and folate status in patients with breast cancer (BC) in order to clarify determinants of hyperhomocysteinemia. The study included 315 BC cases and 604 controls. The MTHFRC677T genotype was associated with an increased incidence of BC [Odds ratio (OR)=1.71; 95% Confidential interval (CI)=1.21-2.43]. The MTHFR A1298C genotype was associated with a decreased risk of BC [OR=0.68; 95% CI: 0.49-0.95]. The homocysteine level was not associated with either MTHFR C677T or A1298C, nor with FTO rs1477196, but was inversely correlated with folate status in cancer cases (p<0.0001) and tended to be higher in patients with the MTHFR 677TT genotype. The folate level (p<0.0005) was an independent predictor of hyper-homocysteinemia in patients with BC. These results suggest an important role of homocysteine in breast tumorigenesis. Further studies are warranted to investigate how combined MTHFR genotypes exert their effects on cancer susceptibility.