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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
Authors: Naushad, Shaik Mohammad
Pavani, Addepalli
Rupasree, Yedluri
Sripurna, Deepti
Gottumukkala, Suryanarayana Raju
Digumarti, Raghunadha Rao
Kutala, Vijay Kumar
Keywords: Catechol-O-methyltransferase (COMT);8-Oxo-2’-deoxyguanosine (8-oxodG);One-carbon metabolism;Oxidative DNA damage;Breast cancer;Polymorphism;Plasma folate
Issue Date: Aug-2011
Publisher: NISCAIR-CSIR, India
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/del6. 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.
Page(s): 283-289
ISSN: 0975-0959 (Online); 0301-1208 (Print)
Appears in Collections:IJBB Vol.48(4) [August 2011]

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