title: Genetic profile and determinants of homocysteine levels in Kazakhstan patients with breast cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  The study included 315 BC cases and 604 controls.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Professor and Chairman, Department of Global Health, Medicine and Welfare, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. takamura@nagasaki-u.ac.jp.
authors.forename: Ainur
authors.initials: A
authors.lastname: Akilzhanova
authors.forename: Zhannur
authors.initials: Z
authors.lastname: Nurkina
authors.forename: Kuvat
authors.initials: K
authors.lastname: Momynaliev
authors.forename: Erlan
authors.initials: E
authors.lastname: Ramanculov
authors.forename: Zhaxibai
authors.initials: Z
authors.lastname: Zhumadilov
authors.forename: Zhaxybai
authors.initials: Z
authors.lastname: Zhumadilov
authors.forename: Tolebay
authors.initials: T
authors.lastname: Rakhypbekov
authors.forename: Naomi
authors.initials: N
authors.lastname: Hayashida
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakashima
authors.forename: Noboru
authors.initials: N
authors.lastname: Takamura
mesh_terms: D000328:Adult; D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007623:Kazakhstan; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*
chemical_list: D011506:Proteins; D006710:Homocysteine; D005492:Folic Acid; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Breast cancer; FTO; Kazakhstan; MTHFR; folate; homocysteine; polymorphism