title: Modulatory effect of plasma folate and polymorphisms in one-carbon metabolism on catecholamine methyltransferase (COMT) H108L associated oxidative DNA damage and breast cancer risk.
abstract: The present study was aimed to investigate the modulatory role of plasma folate and eight putatively functional polymorphisms of one-carbon metabolism on catecholamine methyltransferase (COMT)-mediated oxidative DNA damage and breast cancer risk. Plasma folate and 8-oxo-2'-deoxyguanosine (8-oxodG) were estimated by commercially available kits, while polymorphisms were screened by PCR-RFLP and PCR-AFLP methods. COMT H108L polymorphism showed independent association with breast cancer (OR: 1.73, 95% CI: 1.31-2.30). No significant interaction was observed between folate status and COMT genotype. Multifactor dimensionality reduction (MDR) analysis gave evidence for the significant epistatic (gene-gene) interactions (p<0.0001) of COMT H108L with reduced folate carrier 1 (RFC1) G80A, thymidylate synthase (TYMS) 5'-UTR 3R2R, TYMS 3'-UTR ins6/de16. Increased plasma 8-oxodG were observed in cases compared to controls (mean +/- SE: 5.59 +/- 0.60 vs. 3.50 +/- 0.40 ng/ml, p<0.004). Plasma folate deficiency alone was not a significant predictor of 8-oxodG elevation. The genotype combinations namely, RFC1 G80A/methionine synthase reductase (MTRR) A66G, RFC1 G80A/SHMT C1420T/TYMS 3R2R and serine hydroxymethyltransferase (SHMT) C1420T/TYMS 3R2R/methionine synthase (MTR) A2756G/COMT H108L were strong predictors of 8-oxodG elevation in the order of risk. To conclude, the current study provides substantial evidence for a cross talk between one-carbon metabolism and COMT catalysis that might influence oxidative DNA damage and breast cancer risk.
authors: Department of Clinical Pharmacology & Therapeutics, Nizam's Institute of Medical Sciences (NIMS), Panjagutta, Hyderabad 500082, AP, India.
authors: Shaik Mohammad
authors: SM
authors: Naushad
authors: Addepalli
authors: A
authors: Pavani
authors: Yedluri
authors: Y
authors: Rupasree
authors: Deepti
authors: D
authors: Sripurna
authors: Suryanarayana Raju
authors: SR
authors: Gottumukkala
authors: Raghunadha Rao
authors: RR
authors: Digumarti
authors: Vijay Kumar
authors: VK
authors: Kutala
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004249:DNA Damage; D017931:DNA Primers; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006801:Humans; D010084:Oxidation-Reduction; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D017931:DNA Primers; D005492:Folic Acid; D002394:Catechol O-Methyltransferase