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

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Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusions

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

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Acknowledgments

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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Authors and Affiliations

  1. Department of Epidemiology, University of North Carolina, CB #7435, McGavran-Greenberg Hall, Chapel Hill, NC, 27599-7435, USA

    Lauren E. McCullough, Robert C. Millikan, Kari E. North, Andrew F. Olshan & Marilie D. Gammon

  2. Department of Environmental Health Sciences, Columbia University, New York, NY, USA

    Regina M. Santella

  3. Department of Medicine, University of North Carolina, Chapel Hill, NC, USA

    Rebecca J. Cleveland

  4. Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA

    Patrick T. Bradshaw

  5. Department of Epidemiology, Columbia University, New York, NY, USA

    Sybil M. Eng & Alfred I. Neugut

  6. Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, New York, NY, USA

    Christine B. Ambrosone

  7. Department of Environmental Medicine, New York University, New York, NY, USA

    Jiyoung Ahn

  8. Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, USA

    Susan E. Steck

  9. Department of Community Medicine and Prevention, Mt. Sinai School of Medicine, New York, NY, USA

    Susan L. Teitelbaum

  10. Department of Medicine, Columbia University, New York, NY, USA

    Alfred I. Neugut

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  1. Lauren E. McCullough
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  2. Regina M. Santella
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  3. Rebecca J. Cleveland
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  9. Christine B. Ambrosone
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Correspondence to Lauren E. McCullough.

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McCullough, L.E., Santella, R.M., Cleveland, R.J. et al. Polymorphisms in oxidative stress genes, physical activity, and breast cancer risk. Cancer Causes Control 23, 1949–1958 (2012). https://doi.org/10.1007/s10552-012-0072-1

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  • DOI: https://doi.org/10.1007/s10552-012-0072-1

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