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Manganese superoxide dismutase polymorphism, treatment-related toxicity and disease-free survival in SWOG 8897 clinical trial for breast cancer

  • Epidemiology
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Abstract

To date, the few studies of associations between a functional polymorphism in the oxidative stress-related gene manganese superoxide dismutase (SOD2) and breast cancer survival have been inconsistent. In a homogeneous patient population from a large cooperative group trial Southwest Oncology Group (SWOG) 8897, we evaluated this polymorphism in relation to both treatment-related toxicity and disease-free survival (DFS). Among 458 women who received cyclophosphamide-containing adjuvant chemotherapy, those with variant C alleles, related to higher antioxidant activity, experienced less grade 3–4 neutropenia (OR = 0.52, 95% CI = 0.29–0.92) but had worse DFS (HR = 1.59, 95% CI = 0.99–2.55) than women with TT genotypes. No associations were observed among 874 women who were followed without adjuvant therapy. Our results are consistent with the hypothesis that women with higher SOD2 antioxidant activity may experience less treatment-related toxicity but shorter time to disease recurrence or death after breast cancer adjuvant chemotherapy, supporting the modifying effects of oxidative stress-related enzymes on cancer treatment toxicity and efficacy.

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Acknowledgments

This investigation was supported in part by the following R01 and PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA095222, CA32102, CA38926, CA02599, CA13612, CA22433, CA27057, CA37981, CA46282, CA20319, CA35431, CA76447, CA45560, CA12644, CA14028, CA58416, CA04919, CA35090, CA35176, CA58686, CA58861, CA46113, CA58882, CA35128, CA74647, CA46136, CA45450, CA35261, CA35192, CA12213, CA16385, CA58658, CA46441, CA58723, CA45377, CA35119, CA42777, CA73590, CA114558-02, CA35178, and CA35262. Drs. Ambrosone, Hayes, Hortobagyi, and Rae are recipients of funding from the Breast Cancer Research Foundation. Dr. Yao was partially supported by a Department of Defense award DAMD W81XWH-08-1-0223.

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Authors and Affiliations

  1. Department of Cancer and Prevention and Control, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY, 14263, USA

    Song Yao, Hua Zhao, Warren Davis & Christine B. Ambrosone

  2. Southwest Oncology Group Statistical Center, Seattle, WA, USA

    William E. Barlow

  3. Loyola University Stritch School of Medicine, Maywood, IL, USA

    Kathy S. Albain

  4. PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Korea

    Ji-Yeob Choi

  5. University of Arizona Cancer Center, Tucson, AZ, USA

    Robert B. Livingston

  6. University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA

    James M. Rae & Daniel F. Hayes

  7. University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    I-Tien Yeh & Peter M. Ravdin

  8. University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Laura F. Hutchins

  9. The Angeles Clinic and Research Institute, Santa Monica, CA, USA

    Silvana Martino

  10. Heartland Cancer Research CCOP, Missouri Baptist Medical Center, St. Louis, MO, USA

    Alan P. Lyss

  11. Baylor College of Medicine, Houston, TX, USA

    C. Kent Osborne

  12. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA

    Martin D. Abeloff

  13. University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Gabriel N. Hortobagyi

Authors
  1. Song Yao
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  2. William E. Barlow
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  3. Kathy S. Albain
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  4. Ji-Yeob Choi
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  5. Hua Zhao
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  6. Robert B. Livingston
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  7. Warren Davis
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  8. James M. Rae
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  9. I-Tien Yeh
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  10. Laura F. Hutchins
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  11. Peter M. Ravdin
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  12. Silvana Martino
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  13. Alan P. Lyss
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  14. C. Kent Osborne
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  15. Martin D. Abeloff
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  16. Gabriel N. Hortobagyi
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  17. Daniel F. Hayes
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  18. Christine B. Ambrosone
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Corresponding author

Correspondence to Song Yao.

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Martin D. Abeloff—Deceased.

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Yao, S., Barlow, W.E., Albain, K.S. et al. Manganese superoxide dismutase polymorphism, treatment-related toxicity and disease-free survival in SWOG 8897 clinical trial for breast cancer. Breast Cancer Res Treat 124, 433–439 (2010). https://doi.org/10.1007/s10549-010-0840-0

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  • DOI: https://doi.org/10.1007/s10549-010-0840-0

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