Insights into Pathogenic Interactions Among Environment, Host, and Tumor at the Crossroads of Molecular Pathology and Epidemiology

Evidence indicates that diet, nutrition, lifestyle, the environment, the microbiome, and other exogenous factors have pathogenic roles and also influence the genome, epigenome, transcriptome, proteome, and metabolome of tumor and nonneoplastic cells, including immune cells. With the need for big-data research, pathology must transform to integrate data science fields, including epidemiology, biostatistics, and bioinformatics. The research framework of molecular pathological epidemiology (MPE) demonstrates the strengths of such an interdisciplinary integration, having been used to study breast, lung, prostate, and colorectal cancers. The MPE research paradigm not only can provide novel insights into interactions among environment, tumor, and host but also opens new research frontiers. New developments—such as computational digital pathology, systems biology, artificial intelligence, and in vivo pathology technologies—will further transform pathology and MPE. Although it is necessary to address the rarity of transdisciplinary education and training programs, MPE provides an exemplary model of integrative scientific approaches and contributes to advancements in precision medicine, therapy, and prevention.

Epidemiology of Moderate Alcohol Consumption and Breast Cancer: Association or Causation?

Epidemiological studies have been used to show associations between modifiable lifestyle habits and the incidence of breast cancer. Among such factors, a history of alcohol use has been reported in multiple studies and meta-analyses over the past decades. However, associative epidemiological studies that were interpreted as evidence that even moderate alcohol consumption increases breast cancer incidence have been controversial. In this review, we consider the literature on the relationship between moderate or heavy alcohol use, both in possible biological mechanisms and in variations in susceptibility due to genetic or epigenetic factors. We argue that there is a need to incorporate additional approaches to move beyond the associations that are reported in traditional epidemiological analyses and incorporate information on molecular pathologic signatures as a requirement to posit causal inferences. In particular, we point to the efforts of the transdisciplinary field of molecular pathological epidemiology (MPE) to evaluate possible causal relationships, if any, of alcohol consumption and breast cancer. A wider application of the principles of MPE to this field would constitute a giant step that could enhance our understanding of breast cancer and multiple modifiable risk factors, a step that would be particularly suited to the era of “personalized medicine”.

Colorectal Cancers: An Update on Their Molecular Pathology

Colorectal cancers (CRCs) are the third leading cause of cancer-related mortality worldwide. Rather than being a single, uniform disease type, accumulating evidence suggests that CRCs comprise a group of molecularly heterogeneous diseases that are characterized by a range of genomic and epigenomic alterations. This heterogeneity slows the development of molecular-targeted therapy as a form of precision medicine. Recent data regarding comprehensive molecular characterizations and molecular pathological examinations of CRCs have increased our understanding of the genomic and epigenomic landscapes of CRCs, which has enabled CRCs to be reclassified into biologically and clinically meaningful subtypes. The increased knowledge of the molecular pathological epidemiology of CRCs has permitted their evolution from a vaguely understood, heterogeneous group of diseases with variable clinical courses to characteristic molecular subtypes, a development that will allow the implementation of personalized therapies and better management of patients with CRC. This review provides a perspective regarding recent developments in our knowledge of the molecular and epidemiological landscapes of CRCs, including results of comprehensive molecular characterizations obtained from high-throughput analyses and the latest developments regarding their molecular pathologies, immunological biomarkers, and associated gut microbiome. Advances in our understanding of potential personalized therapies for molecularly specific subtypes are also reviewed.