Etiologic field effect: reappraisal of the field effect concept in cancer predisposition and progression

Paul Lochhead, Andrew T Chan, Reiko Nishihara, Charles S Fuchs, Andrew H Beck, Edward Giovannucci, Shuji Ogino

Research output: Contribution to journalArticle

75 Citations (Scopus)

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.Modern Pathology advance online publication, 13 June 2014; doi:10.1038/modpathol.2014.81.

Original languageEnglish
Pages (from-to)14-29
Number of pages16
JournalModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
Volume28
Issue number1
Early online date13 Jun 2014
DOIs
Publication statusPublished - Jan 2015

Fingerprint

Neoplasms
Molecular Epidemiology
Pathology
Microbial Genetics
Gene-Environment Interaction
Precision Medicine
Tumor Microenvironment
Systems Biology
Metabolome
Environmental Exposure
Biosensing Techniques
Proteome
Prednisolone
Transcriptome
Research
Publications
Life Style
Colorectal Neoplasms
Immunity
Colon

Keywords

  • Cancer
  • Epidemiology
  • Pathogenesis

Cite this

Etiologic field effect : reappraisal of the field effect concept in cancer predisposition and progression. / Lochhead, Paul; Chan, Andrew T; Nishihara, Reiko; Fuchs, Charles S; Beck, Andrew H; Giovannucci, Edward; Ogino, Shuji.

In: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, Vol. 28, No. 1, 01.2015, p. 14-29.

Research output: Contribution to journalArticle

Lochhead, Paul ; Chan, Andrew T ; Nishihara, Reiko ; Fuchs, Charles S ; Beck, Andrew H ; Giovannucci, Edward ; Ogino, Shuji. / Etiologic field effect : reappraisal of the field effect concept in cancer predisposition and progression. In: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2015 ; Vol. 28, No. 1. pp. 14-29.
@article{c6d6e8e656874901b38b5755d2c3fdd4,
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.Modern Pathology advance online publication, 13 June 2014; doi:10.1038/modpathol.2014.81.",
keywords = "Cancer, Epidemiology, Pathogenesis",
author = "Paul Lochhead and Chan, {Andrew T} and Reiko Nishihara and Fuchs, {Charles S} and Beck, {Andrew H} and Edward Giovannucci and Shuji Ogino",
year = "2015",
month = "1",
doi = "10.1038/modpathol.2014.81",
language = "English",
volume = "28",
pages = "14--29",
journal = "Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc",
issn = "1530-0285",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Etiologic field effect

T2 - reappraisal of the field effect concept in cancer predisposition and progression

AU - Lochhead, Paul

AU - Chan, Andrew T

AU - Nishihara, Reiko

AU - Fuchs, Charles S

AU - Beck, Andrew H

AU - Giovannucci, Edward

AU - Ogino, Shuji

PY - 2015/1

Y1 - 2015/1

N2 - 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.Modern Pathology advance online publication, 13 June 2014; doi:10.1038/modpathol.2014.81.

AB - 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.Modern Pathology advance online publication, 13 June 2014; doi:10.1038/modpathol.2014.81.

KW - Cancer

KW - Epidemiology

KW - Pathogenesis

U2 - 10.1038/modpathol.2014.81

DO - 10.1038/modpathol.2014.81

M3 - Article

C2 - 24925058

VL - 28

SP - 14

EP - 29

JO - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

SN - 1530-0285

IS - 1

ER -