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Breast Cancer Research and Treatment

, Volume 121, Issue 2, pp 453–460 | Cite as

Alcohol consumption and breast tumor mitochondrial DNA mutations

  • Mary E. Platek
  • Peter G. Shields
  • Duanjun Tan
  • Catalin Marian
  • Matthew R. Bonner
  • Susan E. McCann
  • Jing Nie
  • Gregory E. Wilding
  • Christine Ambrosone
  • Amy E. Millen
  • Maurizio Trevisan
  • Marcia Russell
  • Thomas H. Nochajski
  • Stephen B. Edge
  • Janet Winston
  • Jo L. Freudenheim
Epidemiology

Abstract

Mitochondrial DNA (mtDNA) mutations are frequent in breast tumors, but the etiology of these mutations is unknown. We hypothesized that these mutations are associated with exposures that affect oxidative stress such as alcohol metabolism. Using archived tumor blocks from incident breast cancer cases in a case control study, the Western New York Exposures and Breast Cancer (WEB) study, analysis of mtDNA mutations was conducted on 128 breast cancer cases selected based on extremes of alcohol intake. Temporal temperature gradient gel electrophoresis (TTGE) was used to screen the entire mtDNA genome and sequencing was completed for all TTGE positive samples. Case–case comparisons were completed using unconditional logistic regression to determine the relative prevalence of the mutations by exposures including alcohol consumption, manganese superoxide dismutase (MnSOD) genotype, nutrient intake related to oxidative stress and established breast cancer risk factors. Somatic mtDNA mutations were found in 60 of the 128 tumors examined. There were no differences in the prevalence of mtDNA mutations by alcohol consumption, MnSOD genotype or dietary intake. The likelihood of mtDNA mutations was reduced among those with a positive family history for breast cancer (OR = 0.33, CI = 0.12–0.92), among postmenopausal women who used hormone replacement therapy (OR = 0.46, CI = 0.19–1.08, P = 0.08) and was increased for ER negative tumors (OR = 2.05, CI = 0.95–4.43, P = 0.07). Consistent with previous studies, we found that mtDNA mutations are a frequent occurrence in breast tumors. An understanding of the etiology of mtDNA mutations may provide insight into breast carcinogenesis.

Keywords

Breast cancer epidemiology Mitochondrial DNA mutations Oxidative stress Alcohol consumption 

Notes

Acknowledgments

This work was funded in part by the Department of Defense grants number DAMD 170310446 and 170010417 and the National Institutes of Health grants number RO1CA092040, P50AA09802 and R25CA114101.

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Mary E. Platek
    • 1
  • Peter G. Shields
    • 2
  • Duanjun Tan
    • 3
  • Catalin Marian
    • 2
  • Matthew R. Bonner
    • 4
  • Susan E. McCann
    • 5
  • Jing Nie
    • 4
  • Gregory E. Wilding
    • 6
  • Christine Ambrosone
    • 5
  • Amy E. Millen
    • 4
  • Maurizio Trevisan
    • 7
  • Marcia Russell
    • 8
  • Thomas H. Nochajski
    • 9
  • Stephen B. Edge
    • 10
  • Janet Winston
    • 11
  • Jo L. Freudenheim
    • 4
  1. 1.Cancer Prevention and Population Sciences, Roswell Park Cancer InstituteBuffaloUSA
  2. 2.Division of Cancer Genetics and Epidemiology, Lombardi Comprehensive Cancer CenterGeorgetown University Medical CenterWashingtonUSA
  3. 3.Department of PathologyState University of New York Downstate Medical CenterBrooklynUSA
  4. 4.Department of Social and Preventive MedicineState University of New York at BuffaloBuffaloUSA
  5. 5.Department of Cancer Prevention and ControlRoswell Park Cancer InstituteBuffaloUSA
  6. 6.Department of BiostatisticsRoswell Park Cancer InstituteBuffaloUSA
  7. 7.University of Nevada Health Sciences SystemLas VegasUSA
  8. 8.Prevention Research CenterBerkeleyUSA
  9. 9.School of Social WorkState University of New York at BuffaloBuffaloUSA
  10. 10.Department of Surgical OncologyRoswell Park Cancer InstituteBuffaloUSA
  11. 11.Potomac HospitalWoodbridgeUSA

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