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Genetic variation in multiple biologic pathways, flavonoid intake, and breast cancer

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Abstract

Purpose

We previously reported an inverse association between flavonoid intake and breast cancer incidence, which has been confirmed by others, but no studies have considered simultaneously potential interactions of flavonoids with multiple genetic polymorphisms involved in biologically relevant pathways (oxidative stress, carcinogen metabolism, DNA repair, and one-carbon metabolism).

Methods

To estimate interaction effects between flavonoids and 13 polymorphisms in these four pathways on breast cancer risk, we used population-based data (n = 875 cases and 903 controls) and several statistical approaches, including conventional logistic regression and semi-Bayesian hierarchical modeling (incorporating prior information on the possible biologic functions of genes), which also provides biologic pathway-specific effect estimates.

Results

Compared to the standard multivariate model, the results from the hierarchical model indicate that gene-by-flavonoid interaction estimates are attenuated, but more precise. In the hierarchical model, the average effect of the deleterious versus beneficial gene, controlling for average flavonoid intake in the DNA repair pathway, and adjusted for the three other biologically relevant pathways (oxidative stress, carcinogen metabolism, and one-carbon metabolism), resulted in a 27 % increase risk for breast cancer [odds ratio = 1.27; 95 % confidence interval (CI) = 0.70, 2.29]. However, the CI was wide.

Conclusions

Based on results from the semi-Bayesian model, breast cancer risk may be influenced jointly by flavonoid intake and genes involved in DNA repair, but our findings require confirmation.

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Acknowledgments

The authors would like to acknowledge Drs. Duncan Thomas and Charles Poole for their comments on previous versions of this analysis. National Institutes of Health (U01CA/ES66572, P30ES10126, P30ES0090809, P50CA58233, R01CA109753, K07CA102640, and T32CA09529); Department of Defense (BC031746 and W81XWH-06-1-0298); and private foundations (Breast Cancer Research Fund and the American Institute for Cancer Research).

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Authors and Affiliations

  1. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Nikhil K. Khankari, Lauren E. McCullough & Marilie D. Gammon

  2. Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Patrick T. Bradshaw

  3. Department of Preventive Medicine, Mount Sinai School of Medicine, New York, NY, 10029, USA

    Susan L. Teitelbaum, Xinran Xu & Jia Chen

  4. Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, 29208, USA

    Susan E. Steck

  5. Department of Public Health and Preventive Medicine, University of Toledo, Toledo, OH, 43614, USA

    Brian N. Fink

  6. Department of Environmental Medicine, New York University, New York, NY, 10016, USA

    Jiyoung Ahn

  7. Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA

    Christine B. Ambrosone

  8. Department of Medicine, Columbia University, New York, NY, 10032, USA

    Katherine D. Crew & Alfred I. Neugut

  9. Department of Epidemiology, Columbia University, New York, NY, 10032, USA

    Mary Beth Terry & Alfred I. Neugut

  10. Department of Environmental Health, Columbia University, New York, NY, 10032, USA

    Regina M. Santella

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  1. Nikhil K. Khankari
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Correspondence to Nikhil K. Khankari.

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Khankari, N.K., Bradshaw, P.T., McCullough, L.E. et al. Genetic variation in multiple biologic pathways, flavonoid intake, and breast cancer. Cancer Causes Control 25, 215–226 (2014). https://doi.org/10.1007/s10552-013-0324-8

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