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Bayesian Modeling of Complex Metabolic Pathways

Many chronic diseases are the result of a complex sequence of biochemical reactions involving exposures to various environmental agents, metabolized by a number of different genes. Routine epidemiologic analyses of such associations have tended to rely on standard contingency table or logistic regression methods, typically focusing on one variable at a time or pairwise combinations. We consider two statistical alternatives to this approach, one based on Bayesian model averaging, one based on pharmacokinetic modeling of the biochemical pathways. These approaches are illustrated using data from a case-control study of colorectal polyps in relation to tobacco smoking and consumption of well done red meat, both viewed as sources of heterocyclic amines and polycyclic aromatic hydrocarbons. The new analyses are structured in a manner that attempts to take advantage of prior knowledge of the metabolism of these classes of compounds and the various genes that regulate these pathways.