Cancer Causes & Control

, Volume 23, Issue 12, pp 1949–1958 | Cite as

Polymorphisms in oxidative stress genes, physical activity, and breast cancer risk

  • Lauren E. McCullough
  • Regina M. Santella
  • Rebecca J. Cleveland
  • Patrick T. Bradshaw
  • Robert C. Millikan
  • Kari E. North
  • Andrew F. Olshan
  • Sybil M. Eng
  • Christine B. Ambrosone
  • Jiyoung Ahn
  • Susan E. Steck
  • Susan L. Teitelbaum
  • Alfred I. Neugut
  • Marilie D. Gammon
Original paper



The mechanisms driving the physical activity–breast cancer association are unclear. Exercise both increases reactive oxygen species production, which may transform normal epithelium to a malignant phenotype, and enhances antioxidant capacity, which could protect against subsequent oxidative insult. Given the paradoxical effects of physical activity, the oxidative stress pathway is of interest. Genetic variation in CAT or antioxidant-related polymorphisms may mediate the physical activity–breast cancer association.


We investigated the main and joint effects of three previously unreported polymorphisms in CAT on breast cancer risk. We also estimated interactions between recreational physical activity (RPA) and 13 polymorphisms in oxidative stress-related genes. Data were from the Long Island Breast Cancer Study Project, with interview and biomarker data available on 1,053 cases and 1,102 controls.


Women with ≥1 variant allele in CAT rs4756146 had a 23 % reduced risk of postmenopausal breast cancer compared with women with the common TT genotype (OR = 0.77; 95 % CI = 0.59–0.99). We observed two statistical interactions between RPA and genes in the antioxidant pathway (p = 0.043 and 0.006 for CAT and GSTP1, respectively). Highly active women harboring variant alleles in CAT rs1001179 were at increased risk of breast cancer compared with women with the common CC genotype (OR = 1.61; 95 % CI, 1.06–2.45). Risk reductions were observed among moderately active women carrying variant alleles in GSTP1 compared with women homozygous for the major allele (OR = 0.56; 95 % CI, 0.38–0.84).


Breast cancer risk may be jointly influenced by RPA and genes involved in the antioxidant pathway, but our findings require confirmation.


Breast cancer Epidemiology Catalase Physical activity Oxidative stress 



This work was supported in part by grants from the National Cancer Institute and the National Institutes of Environmental Health and Sciences (Grant nos. UO1CA/ES66572, P30ES009089, and P30ES10126), the Department of Defense (Grant no. BC093608), and the University of North Carolina Lineberger Comprehensive Cancer Center Breast Cancer SPORE (Grant no. P50CA058223). Drs. Santella and Ambrosone are recipients of funding from the Breast Cancer Research Foundation.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Lauren E. McCullough
    • 1
  • Regina M. Santella
    • 2
  • Rebecca J. Cleveland
    • 3
  • Patrick T. Bradshaw
    • 4
  • Robert C. Millikan
    • 1
  • Kari E. North
    • 1
  • Andrew F. Olshan
    • 1
  • Sybil M. Eng
    • 5
  • Christine B. Ambrosone
    • 6
  • Jiyoung Ahn
    • 7
  • Susan E. Steck
    • 8
  • Susan L. Teitelbaum
    • 9
  • Alfred I. Neugut
    • 5
    • 10
  • Marilie D. Gammon
    • 1
  1. 1.Department of EpidemiologyUniversity of North CarolinaChapel HillUSA
  2. 2.Department of Environmental Health SciencesColumbia UniversityNew YorkUSA
  3. 3.Department of MedicineUniversity of North CarolinaChapel HillUSA
  4. 4.Department of NutritionUniversity of North CarolinaChapel HillUSA
  5. 5.Department of EpidemiologyColumbia UniversityNew YorkUSA
  6. 6.Division of Cancer Prevention and Population SciencesRoswell Park Cancer InstituteNew YorkUSA
  7. 7.Department of Environmental MedicineNew York UniversityNew YorkUSA
  8. 8.Department of Epidemiology and BiostatisticsUniversity of South CarolinaColumbiaUSA
  9. 9.Department of Community Medicine and PreventionMt. Sinai School of MedicineNew YorkUSA
  10. 10.Department of MedicineColumbia UniversityNew YorkUSA

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