Review Article: The Role of Molecular Pathological Epidemiology in the Study of Neoplastic and Non-neoplastic Diseases in the Era of Precision Medicine - PubMed
doi: 10.1097/EDE.0000000000000471.
Reiko Nishihara, Tyler J VanderWeele, Molin Wang, Akihiro Nishi, Paul Lochhead, Zhi Rong Qian, Xuehong Zhang, Kana Wu, Hongmei Nan, Kazuki Yoshida, Danny A Milner Jr, Andrew T Chan, Alison E Field, Carlos A Camargo Jr, Michelle A Williams, Edward L Giovannucci
Affiliations
- PMID: 26928707
- PMCID: PMC4892980
- DOI: 10.1097/EDE.0000000000000471
Review Article: The Role of Molecular Pathological Epidemiology in the Study of Neoplastic and Non-neoplastic Diseases in the Era of Precision Medicine
Shuji Ogino et al. Epidemiology. 2016 Jul.
Abstract
Molecular pathology diagnostics to subclassify diseases based on pathogenesis are increasingly common in clinical translational medicine. Molecular pathological epidemiology (MPE) is an integrative transdisciplinary science based on the unique disease principle and the disease continuum theory. While it has been most commonly applied to research on breast, lung, and colorectal cancers, MPE can investigate etiologic heterogeneity in non-neoplastic diseases, such as cardiovascular diseases, obesity, diabetes mellitus, drug toxicity, and immunity-related and infectious diseases. This science can enhance causal inference by linking putative etiologic factors to specific molecular biomarkers as outcomes. Technological advances increasingly enable analyses of various -omics, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, microbiome, immunomics, interactomics, etc. Challenges in MPE include sample size limitations (depending on availability of biospecimens or biomedical/radiological imaging), need for rigorous validation of molecular assays and study findings, and paucities of interdisciplinary experts, education programs, international forums, and standardized guidelines. To address these challenges, there are ongoing efforts such as multidisciplinary consortium pooling projects, the International Molecular Pathological Epidemiology Meeting Series, and the Strengthening the Reporting of Observational Studies in Epidemiology-MPE guideline project. Efforts should be made to build biorepository and biobank networks, and worldwide population-based MPE databases. These activities match with the purposes of the Big Data to Knowledge (BD2K), Genetic Associations and Mechanisms in Oncology (GAME-ON), and Precision Medicine Initiatives of the United States National Institute of Health. Given advances in biotechnology, bioinformatics, and computational/systems biology, there are wide open opportunities in MPE to contribute to public health.
Conflict of interest statement
Conflict of Interest: ATC previously served as a consultant for Bayer Healthcare, Millennium Pharmaceuticals, Pozen Inc, and Pfizer Inc. The work was not funded by Bayer Healthcare, Millennium Pharmaceuticals, Pozen Inc, or Pfizer Inc. All of the other authors declare no conflict of interest.
Figures

Hypothesis evaluation in molecular pathological epidemiology (MPE). Here, the simplest disease subtyping system with binary subtypes A and B is shown. Note that disease subtyping systems are often more complex than simple dichotomy. Hypothesis evaluation #1 or #2 is on the relationship between an exposure of interest and subtype A or B, respectively. Hypothesis evaluation #3 is unique to MPE, and concerns on a difference (heterogeneity) between the relationship of the exposure with subtype A and that with subtype B. Hence, this hypothesis evaluation #3 is referred to as “heterogeneity hypothesis evaluation” or “heterogeneity evaluation”. See the text for further explanation.

Complex hypothesis evaluation in molecular pathological epidemiology (MPE). Here, shown as an example, the disease subtyping system is ordinal, and more complex than simple dichotomy. Hypothesis evaluation #3 concerns on a difference (heterogeneity) between the relationships of the exposure with ordinal subtypes according to the level of the subtyping biomarker in MPE research. Hence, this heterogeneity evaluation needs to address the ordinal nature of subtyping system. See the text for further explanation.
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