Molecular pathological epidemiology: new developing frontiers of big data science to study etiologies and pathogenesis

Abstract

Molecular pathological epidemiology (MPE) is an integrative field that utilizes molecular pathology to incorporate interpersonal heterogeneity of a disease process into epidemiology. In each individual, the development and progression of a disease are determined by a unique combination of exogenous and endogenous factors, resulting in different molecular and pathological subtypes of the disease. Based on “the unique disease principle,” the primary aim of MPE is to uncover an interactive relationship between a specific environmental exposure and disease subtypes in determining disease incidence and mortality. This MPE approach can provide etiologic and pathogenic insights, potentially contributing to precision medicine for personalized prevention and treatment. Although breast, prostate, lung, and colorectal cancers have been among the most commonly studied diseases, the MPE approach can be used to study any disease. In addition to molecular features, host immune status and microbiome profile likely affect a disease process, and thus serve as informative biomarkers. As such, further integration of several disciplines into MPE has been achieved (e.g., pharmaco-MPE, immuno-MPE, and microbial MPE), to provide novel insights into underlying etiologic mechanisms. With the advent of high-throughput sequencing technologies, available genomic and epigenomic data have expanded dramatically. The MPE approach can also provide a specific risk estimate for each disease subgroup, thereby enhancing the impact of genome-wide association studies on public health. In this article, we present recent progress of MPE, and discuss the importance of accounting for the disease heterogeneity in the era of big-data health science and precision medicine.

Association of Dietary Patterns With Risk of Colorectal Cancer Subtypes Classified by Fusobacterium nucleatum in Tumor Tissue

“…Notably, molecular subtyping in the MPE approach can gather pathogenetically similar cases, and thus can enhance statistical inference (even with a relatively small number of cases). 46 The current study represents emerging unique microbial MPE research, 47 where the microbial feature in tumor tissue can serve as a pathogenic signature.…”

The associations between five polymorphisms of vascular endothelial growth factor and renal cell carcinoma risk: an updated meta-analysis

“…Molecular pathological epidemiology (MPE) is an integrative field that is based on the disease continuum theory and the unique disease principle, which can give clues to analyze the risk factors of diseases 42,43. For example, an MPE study assessed the joint effects of genetic polymorphisms in the mammalian target of rapamycin pathway and epidemiologic risk factors on RCC risk and showed that obesity played a vital role in enhancing RCC risk during the life course 44.…”

Progress of research on microRNAs with diagnostic value in asbestos exposure: A call for method standardization

“…This novel discipline, which has been defined as "epidemiology of molecular pathology and heterogeneity of disease" (16), straddles traditional pathology and epidemiology and assesses how particular exposures influence disease risk through the search for and evaluation of molecular pathological markers also in relation to exogenous (e.g. exposure) and endogenous factors (17,18). Under the umbrella of the "the unique disease principle" (19), MPE is intertwined with precision medicine (16,20) and is the research branch capable of identifying potential biomarkers for the new frontier of personalized medicine (21).…”