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

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• 作者：Nikhil K. Khankari (1)
  Patrick T. Bradshaw (2)
  Lauren E. McCullough (1)
  Susan L. Teitelbaum (3)
  Susan E. Steck (4)
  Brian N. Fink (5)
  Xinran Xu (3)
  Jiyoung Ahn (6)
  Christine B. Ambrosone (7)
  Katherine D. Crew (8)
  Mary Beth Terry (9)
  Alfred I. Neugut (8) (9)
  Jia Chen (3)
  Regina M. Santella (10)
  Marilie D. Gammon (1)
  
• 关键词：Dietary flavonoid intake ; Breast cancer ; Genetic polymorphisms ; Hierarchical model
• 刊名：Cancer Causes and Control
• 出版年：2014
• 出版时间：February 2014
• 年：2014
• 卷：25
• 期：2
• 页码：215-226
• 全文大小：284 KB
• 作者单位：Nikhil K. Khankari (1)
  Patrick T. Bradshaw (2)
  Lauren E. McCullough (1)
  Susan L. Teitelbaum (3)
  Susan E. Steck (4)
  Brian N. Fink (5)
  Xinran Xu (3)
  Jiyoung Ahn (6)
  Christine B. Ambrosone (7)
  Katherine D. Crew (8)
  Mary Beth Terry (9)
  Alfred I. Neugut (8) (9)
  Jia Chen (3)
  Regina M. Santella (10)
  Marilie D. Gammon (1)
  
  1. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
  2. Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
  3. Department of Preventive Medicine, Mount Sinai School of Medicine, New York, NY, 10029, USA
  4. Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, 29208, USA
  5. Department of Public Health and Preventive Medicine, University of Toledo, Toledo, OH, 43614, USA
  6. Department of Environmental Medicine, New York University, New York, NY, 10016, USA
  7. Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA
  8. Department of Medicine, Columbia University, New York, NY, 10032, USA
  9. Department of Epidemiology, Columbia University, New York, NY, 10032, USA
  10. Department of Environmental Health, Columbia University, New York, NY, 10032, USA
  
• ISSN：1573-7225

文摘

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.