%0 Journal Article
%T Association of MTHFR gene polymorphisms with breast cancer survival
%A Damali N Martin
%A Brenda J Boersma
%A Tiffany M Howe
%A Julie E Goodman
%A Leah E Mechanic
%A Stephen J Chanock
%A Stefan Ambs
%J BMC Cancer
%D 2006
%I BioMed Central
%R 10.1186/1471-2407-6-257
%X African-American (n = 143) and Caucasian (n = 105) women, who had incident breast cancer with surgery, were recruited between 1993 and 2003 from the greater Baltimore area, Maryland, USA. Kaplan-Meier survival and multivariate Cox proportional hazards regression analyses were used to examine the relationship between MTHFR SNPs and disease-specific survival.We observed opposite effects of the MTHFR polymorphisms A1298C and C677T on breast cancer survival. Carriers of the variant allele at codon 1298 (A/C or C/C) had reduced survival when compared to homozygous carriers of the common A allele [Hazard ratio (HR) = 2.05; 95% confidence interval (CI), 1.05¨C4.00]. In contrast, breast cancer patients with the variant allele at codon 677 (C/T or T/T) had improved survival, albeit not statistically significant, when compared to individuals with the common C/C genotype (HR = 0.65; 95% CI, 0.31¨C1.35). The effects were stronger in patients with estrogen receptor-negative tumors (HR = 2.70; 95% CI, 1.17¨C6.23 for A/C or C/C versus A/A at codon 1298; HR = 0.36; 95% CI, 0.12¨C1.04 for C/T or T/T versus C/C at codon 677). Interactions between the two MTHFR genotypes and race/ethnicity on breast cancer survival were also observed (A1298C, pinteraction = 0.088; C677T, pinteraction = 0.026).We found that the MTHFR SNPs, C677T and A1298C, were associated with breast cancer survival. The variant alleles had opposite effects on disease outcome in the study population. Race/ethnicity modified the association between the two SNPs and breast cancer survival.Epidemiologic evidence shows that folate deficiency is a breast cancer risk factor [1,2]. MTHFR is a key enzyme in the folate metabolism pathway and regulates the intracellular folate pool for synthesis and methylation of DNA [3,4]. Two common allele variants of the MTHFR gene have been described, C677T (NCBI SNP ID: rs1801133) and A1298C (rs1801131), that lead to amino acid substitutions, Ala222Val and Glu429Ala, and to decreased enzyme a
%U http://www.biomedcentral.com/1471-2407/6/257