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Molecular and Cellular Biochemistry

, Volume 349, Issue 1–2, pp 159–167 | Cite as

Aberrations in one-carbon metabolism induce oxidative DNA damage in sporadic breast cancer

  • Naushad Shaik Mohammad
  • Rupasree Yedluri
  • Pavani Addepalli
  • Suryanarayana Raju Gottumukkala
  • Raghunadha Rao Digumarti
  • Vijay Kumar KutalaEmail author
Article

Abstract

The authors investigated the role of dietary micronutrients and eight functional polymorphisms of one-carbon metabolism in modulating oxidative stress in sporadic breast cancer. PCR-restriction fragment length polymorphism (RFLP) and PCR-amplified fragment length polymorphism (AFLP) methods were used for genetic analysis in 222 sporadic breast cancer cases and 235 controls. Standardized food frequency questionnaire was used for dietary micronutrient assessment. 8-oxo-2′-deoxyguanosine (8-oxodG), folate, and estradiol were estimated using commercial ELISA kits. Reverse-phase HPLC coupled with fluorescence detector was used for plasma homocysteine analysis. Total glutathione was estimated using Ellman’s method. Reduced folate carrier 1 (RFC1) G80A and methylenetetrahydrofolate reductase (MTHFR) C677T were associated with risks of 1.34 (95% CI 1.01–1.79)- and 1.84 (95% CI 1.14–3.00)-folds, respectively, for sporadic breast cancer while cytosolic serine hydroxymethyl transferase (cSHMT) C1420T was associated with reduced risk (OR 0.71, 95% CI 0.53–0.94). Significant increase in plasma 8-oxo-2′-deoxyguanosine (P < 0.004) and homocysteine (P < 0.0001); and significant decrease in total glutathione (P < 0.01) and dietary folate (P = 0.006) was observed in cases than in controls. Oxidative DNA damage showed direct association with menopause (P = 0.02), RFC1 G80A (P < 0.05) and homocysteine (P < 0.0001); and inverse association with dietary folate (P < 0.0001), plasma folate (P < 0.0001), cSHMT C1420T (P < 0.05) and glutathione (P < 0.001). To conclude, the aberrations in one-carbon metabolism induce oxidative stress in sporadic breast cancer either by affecting the folate pool or by impairing remethylation.

Keywords

Sporadic breast cancer 8-oxo-2′-deoxyguanosine One-carbon metabolism Polymorphisms Dietary micronutrients 

Abbreviations

8-oxodG

8-Oxo-2′-deoxyguanosine

AFLP

Amplified fragment length polymorphism

E2

Estradiol

GCPII

Glutamate carboxypeptidase II

MTR

Methionine synthase

MTRR

Methionine synthase reductase

MTHF

Methylene tetrahydrofolate

MTHFR

Methylenetetrahydrofolate reductase

PCR

Polymerase chain reaction

RFC1

Reduced folate carrier 1

RFLP

Restriction fragment length polymorphism

cSHMT

Cytosolic serine hydroxymethyltransferase

tHcy

Total plasma Homocysteine

THF

Tetrahydrofolate

TYMS

Thymidylate synthase

Notes

Acknowledgment

This study was supported by the grant funded by Indian Council of Medical Research (ICMR), New Delhi (Ref No. 5/13/32/2007).

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Naushad Shaik Mohammad
    • 1
  • Rupasree Yedluri
    • 1
  • Pavani Addepalli
    • 1
  • Suryanarayana Raju Gottumukkala
    • 2
  • Raghunadha Rao Digumarti
    • 3
  • Vijay Kumar Kutala
    • 1
    Email author
  1. 1.Departments of Clinical Pharmacology and TherapeuticsNizam’s Institute of Medical SciencesHyderabadIndia
  2. 2.Surgical OncologyNizam’s Institute of Medical SciencesHyderabadIndia
  3. 3.Medical OncologyNizam’s Institute of Medical SciencesHyderabadIndia

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