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Cancer Prevention Research
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Commentary

Mendelian Randomization: How It Can—and Cannot—Help Confirm Causal Relations between Nutrition and Cancer

Arthur Schatzkin, Christian C. Abnet, Amanda J. Cross, Marc Gunter, Ruth Pfeiffer, Mitchell Gail, Unhee Lim and George Davey-Smith
Arthur Schatzkin
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Christian C. Abnet
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Amanda J. Cross
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Marc Gunter
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Ruth Pfeiffer
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Mitchell Gail
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Unhee Lim
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George Davey-Smith
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DOI: 10.1158/1940-6207.CAPR-08-0070 Published February 2009
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    Fig. 1

    A directed acyclic graph depicting how the instrumental variables approach is used in Mendelian randomization. Specifically, Z is the genotype, X is a nutritional exposure, Y is cancer outcome, and C, which is associated with both X and Y, is a potential confounder of an observed association between X and Y. A key assumption underlying the use of instrumental variables in the Mendelian randomization setting is that the association between genotype (Z) and cancer (Y) exists only because the genotype is associated with the nutritional exposure (X); that is, Z is independent of outcome Y given X. This is indicated by the dotted line from Z to Y.

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    Fig. 2

    A directed acyclic graph depicting how the LCT gene can be used as a proxy (instrumental variable) for dairy product intake in a Mendelian randomization study of prostate cancer.

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    Fig. 3

    A directed acyclic graph depicting how the HFE gene can be used as a proxy (instrumental variable) for serum ferritin in a Mendelian randomization study of cancer.

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    Summary case-control data for sample size calculations

    Marker genotypeTotal
    aaaAAA
    Casesr0r1r2R
    Controlss0s1s2S
    Total countsn0n1n2N
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Cancer Prevention Research: 2 (2)
February 2009
Volume 2, Issue 2
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Mendelian Randomization: How It Can—and Cannot—Help Confirm Causal Relations between Nutrition and Cancer
Arthur Schatzkin, Christian C. Abnet, Amanda J. Cross, Marc Gunter, Ruth Pfeiffer, Mitchell Gail, Unhee Lim and George Davey-Smith
Cancer Prev Res February 1 2009 (2) (2) 104-113; DOI: 10.1158/1940-6207.CAPR-08-0070

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Mendelian Randomization: How It Can—and Cannot—Help Confirm Causal Relations between Nutrition and Cancer
Arthur Schatzkin, Christian C. Abnet, Amanda J. Cross, Marc Gunter, Ruth Pfeiffer, Mitchell Gail, Unhee Lim and George Davey-Smith
Cancer Prev Res February 1 2009 (2) (2) 104-113; DOI: 10.1158/1940-6207.CAPR-08-0070
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  • Article
    • Abstract
    • Nutrition and Cancer—the Problem
    • Why the Uncertainty in Nutrition and Cancer?
    • The Mendelian Randomization Strategy
    • How Does Mendelian Randomization Deal with Potential Bias in Observational Epidemiologic Studies?
    • How Do Genes Give Us Information on Nutritional Exposure?
    • Complexities of the Mendelian Randomization Strategy
    • Statistical Power and Sample Size
    • What Mendelian Randomization Is Not
    • Nutrition-Gene Interactions
    • Conclusion
    • Disclosure of Potential Conflicts of Interest
    • Appendix 1. Sample Sizes for Mendelian Randomization Case-Control Studies
    • Footnotes
    • References
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Cancer Prevention Research
eISSN: 1940-6215
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