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Indian Journal of Biochemistry and Biophysics (IJBB) >
IJBB Vol.48 [2011] >
IJBB Vol.48(4) [August 2011] >
| 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 |
| CC License: |  CC Attribution-Noncommercial-No Derivative Works 2.5 India |
| ISSN: | 0975-0959 (Online); 0301-1208 (Print) |
| Source: | IJBB Vol.48(4) [August 2011]
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