title: Haplotypes of the MTHFR gene are associated with an increased risk of breast cancer in a Han Chinese population in Gansu province.
abstract: Elevated homocysteine levels are a risk factor for breast cancer, although the mechanism underlying this effect is unknown. Genome-wide association studies were used to systematically identify genetic variants which were significantly associated with the circulating homocysteine concentration. To examine the role of homocysteine-related variants in the occurrence of breast cancer, we investigated the association between these variants and breast cancer in a Han Chinese population. Five variants of genome-wide significant homocysteine-related genes were selected for the analysis in a case-control study, with a total of 487 patients with breast cancer and 605 controls. We found that none of the studied polymorphisms were related to the altered breast cancer risk. In the haplotypic analysis, the 5,10-methylenetetrahydrofolate reductase (MTHFR) haplotypes rs12085006A/rs1999594G/rs1801133C (OR = 3.44, 95% CI = 1.58-7.50, P = 0.0019) and rs12085006A/rs1999594G/rs1801133T (OR = 16.21, 95% CI = 2.19- 120.32, P = 0.0065) were significantly associated with an increased breast cancer risk when compared with the wild-type haplotype. Both of the risky MTHFR haplotypes were correlated with decreased MTHFR gene expression and elevated homocysteine concentrations, indicating a genetic component for hyperhomocysteinemia. The MTHFR haplotypes reconstructed with homocysteine-related variants were associated with the occurrence of breast cancer. This finding further emphasizes the importance of homocysteine metabolism genes in breast carcinogenesis and highlights the interplay of diet, genetics, and human cancers. © 2016 IUBMB Life, 68(7):526-534, 2016.
authors.affiliation: Key Laboratory of Digestive System Tumors of Gansu Province, Gansu, People's Republic of China.|Depertment of Surgery, The Second Hospital of Lanzhou University, Lanzhou, Gansu, People's Republic of China.
authors.forename: Ailing
authors.initials: A
authors.lastname: Song
authors.affiliation: Key Laboratory of Digestive System Tumors of Gansu Province, Gansu, People's Republic of China.|Depertment of Surgery, The Second Hospital of Lanzhou University, Lanzhou, Gansu, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Digestive System Tumors of Gansu Province, Gansu, People's Republic of China.|Depertment of Surgery, The Second Hospital of Lanzhou University, Lanzhou, Gansu, People's Republic of China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Depertment of Breast Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.affiliation: Key Laboratory of Digestive System Tumors of Gansu Province, Gansu, People's Republic of China.|Depertment of Surgery, The Second Hospital of Lanzhou University, Lanzhou, Gansu, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Digestive System Tumors of Gansu Province, Gansu, People's Republic of China.|Depertment of Surgery, The Second Hospital of Lanzhou University, Lanzhou, Gansu, People's Republic of China.
authors.forename: Xiaokang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Depertment of Surgery, The Second Hospital of Lanzhou University, Lanzhou, Gansu, People's Republic of China.
authors.forename: Shen
authors.initials: S
authors.lastname: Lan
mesh_terms: D000328:Adult; D044466:Asian People; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006710:Homocysteine / Q000235:genetics; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D006710:Homocysteine; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: MTHFR; breast cancer; haplotype; homocysteine; polymorphism