Genetic polymorphisms in folate and alcohol metabolism and breast cancer risk: a case–control study in Thai women
- 538 Downloads
Dietary folate as well as polymorphic variants in one-carbon metabolism genes may modulate risk of breast cancer through aberrant DNA methylation and altered nucleotide synthesis and repair. Alcohol is well recognized as a risk factor for breast cancer, and interactions with one-carbon metabolism has also been suggested. The purpose of this study is to test the hypothesis that genetic polymorphisms in the folate and alcohol metabolic pathway are associated with breast cancer risk. Twenty-seven single nucleotide polymorphisms (SNPs) in the MTR, MTRR, MTHFR, TYMS, ADH1C, ALDH2, GSTP1, NAT1, NAT2, CYP2E1 DRD2, DRD3, and SLC6A4 were genotyped. Five hundred and seventy patients with histopathogically confirmed breast cancer and 497 controls were included in the present study. Association of genotypes with breast cancer risk was evaluated using multivariate logistic regression to estimate odds ratios (OR) and their 95% confidence intervals (95% CI). Increased risk was observed for homozygotes at the MTR SNPs (rs1770449 and rs1050993) with the OR = 2.21 (95% CI 1.18–4.16) and OR = 2.24 (95% CI 1.19–4.22), respectively. A stratified analysis by menopausal status indicated the association between the NAT2 SNP (rs1799930) and breast cancer was mainly evident in premenopausal women (OR 2.70, 95% CI 1.20–6.07), while the MTRR SNP (rs162049) was significant in postmenopausal women (OR 1.61, 95% CI 1.07–2.44). Furthermore, SNPs of the genes that contribute to alcohol behavior, DRD3 (rs167770), DRD2 (rs10891556), and SLC6A4 (rs140701), were also associated with an increased risk of breast cancer. No gene–gene or gene–environment interactions were observed in this study. Our results suggest that genetic polymorphisms in folate and alcohol metabolic pathway influence the risk of breast cancer in Thai population.
KeywordsBreast cancer Folate Alcohol Metabolizing enzyme Single nucleotide polymorphisms
We express our sincere thanks to all patients, recruited control subjects, doctors, nurses, and paramedical personnel of National Cancer Institute, Thailand for their kind participation. This work was supported by the program for promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NiBio 05-41), Japan. S. Sangrajrang is an awardee of a fellowship from Foundation for Promotion of Cancer Research.
- 5.Smith-Warner SA, Spiegelman D, Yaun SS, van den Brandt PA, Folsom AR, Goldbohm RA, Graham S, Holmberg L, Howe GR, Marshall JR, Miller AB, Potter JD, Speizer FE, Willett WC, Wolk A, Hunter DJ (1998) Alcohol and breast cancer in women: a pooled analysis of cohort studies. JAMA 279(7):535–540CrossRefPubMedGoogle Scholar
- 15.Yoshimura K, Hanaoka T, Ohnami S, Ohnami S, Kohno T, Liu Y, Yoshida T, Sakamoto H, Tsugane S (2003) Allele frequencies of single nucleotide polymorphisms (SNPs) in 40 candidate genes for gene-environment studies on cancer: data from population-based Japanese random samples. J Hum Genet 48(12):654–658CrossRefPubMedGoogle Scholar
- 22.Linnebank M, Schmidt S, Kölsch H, Linnebank A, Heun R, Schmidt-Wolf IG, Glasmacher A, Fliessbach K, Klockgether T, Schlegel U, Pels H (2004) The methionine synthase polymorphism D919G alters susceptibility to primary central nervous system lymphoma. Br J Cancer 90(10):1969–1971CrossRefPubMedGoogle Scholar
- 36.Philibert RA, Sandhu H, Hollenbeck N, Gunter T, Adams W, Madan A (2008) The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies. Am J Med Genet B 147B(5):543–549CrossRefGoogle Scholar