title: Etiologic field effect: reappraisal of the field effect concept in cancer predisposition and progression.
abstract: The term 'field effect' (also known as field defect, field cancerization, or field carcinogenesis) has been used to describe a field of cellular and molecular alteration, which predisposes to the development of neoplasms within that territory. We explore an expanded, integrative concept, 'etiologic field effect', which asserts that various etiologic factors (the exposome including dietary, lifestyle, environmental, microbial, hormonal, and genetic factors) and their interactions (the interactome) contribute to a tissue microenvironmental milieu that constitutes a 'field of susceptibility' to neoplasia initiation, evolution, and progression. Importantly, etiological fields predate the acquisition of molecular aberrations commonly considered to indicate presence of filed effect. Inspired by molecular pathological epidemiology (MPE) research, which examines the influence of etiologic factors on cellular and molecular alterations during disease course, an etiologically focused approach to field effect can: (1) broaden the horizons of our inquiry into cancer susceptibility and progression at molecular, cellular, and environmental levels, during all stages of tumor evolution; (2) embrace host-environment-tumor interactions (including gene-environment interactions) occurring in the tumor microenvironment; and, (3) help explain intriguing observations, such as shared molecular features between bilateral primary breast carcinomas, and between synchronous colorectal cancers, where similar molecular changes are absent from intervening normal colon. MPE research has identified a number of endogenous and environmental exposures which can influence not only molecular signatures in the genome, epigenome, transcriptome, proteome, metabolome and interactome, but also host immunity and tumor behavior. We anticipate that future technological advances will allow the development of in vivo biosensors capable of detecting and quantifying 'etiologic field effect' as abnormal network pathology patterns of cellular and microenvironmental responses to endogenous and exogenous exposures. Through an 'etiologic field effect' paradigm, and holistic systems pathology (systems biology) approaches to cancer biology, we can improve personalized prevention and treatment strategies for precision medicine.
authors.affiliation: Gastrointestinal Research Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Lochhead
authors.affiliation: 1] Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
authors.affiliation: 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA [2] Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Reiko
authors.initials: R
authors.lastname: Nishihara
authors.affiliation: 1] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [2] Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Beck
authors.affiliation: 1] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [2] Department of Nutrition, Harvard School of Public Health, Boston, MA, USA [3] Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.affiliation: 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA [2] Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA [3] Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Shuji
authors.initials: S
authors.lastname: Ogino
mesh_terms: D000818:Animals; D018450:Disease Progression; D006801:Humans; D009369:Neoplasms / Q000209:etiology* / Q000473:pathology*