Journal
CARCINOGENESIS
Volume 36, Issue -, Pages S254-S296Publisher
OXFORD UNIV PRESS
DOI: 10.1093/carcin/bgv039
Keywords
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Categories
Funding
- National Institute of Health-National Institute of Environmental Health Sciences (NIEHS) [R13ES023276]
- California Breast Cancer Research Program
- Clarence Heller Foundation
- California Pacific Medical Center Foundation
- University of Sultan Zainal Abidin, Malaysia
- Rutgers Cancer Institute of New Jersey
- Research Council of Norway (RCN) through its Centres of Excellence funding scheme [223268/F50]
- Spanish Ministry of Economy and Competitivity, ISCIII [Fis: PI12/00137, RTICC: RD12/0036/0028]
- FEDER from Regional Development European Funds (European Union)
- Consejeria de Ciencia e Innovacion [CTS-1848]
- Consejeria de Salud of the Junta de Andalucia [PI-0306-2012]
- Ministerio de Educacion y Ciencia (Juande la Cierva' programme) of the Spanish Government
- Italian Ministry of University and Research [2009FZZ4XM_002]
- University of Florence
- University of Oslo
- Emilia-Romagna Region - Project 'Supersite' in Italy
- Fonds de recherche du Quebec-Sante (FRQ-S)
- Fondazione Cariplo in Milan, Italy [2011-0370]
- National Institutes of Health (NIH-NIMHD) [G12MD007581]
- Burroughs Wellcome Fund Postdoctoral Enrichment Award
- Timor Biology Training grant [NIH T32CA09151]
- United States Department of Health and Human Services, NIH [R01 CA170378 PQ22, RO1 CA184384, U54 CA149145, U54 CA151459, P50 CA114747, 1121 CA169964]
- CONACyT [152473]
- AIRC (Italian Association for Cancer Research) [IG 14640]
- Sardinian Regional Government (RAS)
- Public Problem-Solving Program [NRF-015M3C8A6A06014500]
- National Research Foundation of Korea (NRF) [2013M2B2A9A03051296, 2010-0018545]
- Ministry of Education, Science and Technology (MEST) in Korea
- Kuwait Foundation for the Advancement of Sciences [2011-1302-06]
- SysBioNet, a grant for the Italian Roadmap of European Strategy Forum on Research Infrastructures (ESFRI)
- AIRC (Associazione Italiana Ricerca sul Cancro) [IG 15364]
- Rosemere Cancer Foundation
- New Jersey Health Foundation
- Fondo Nacional de Ciencia y Tecnologia (FONDECYT), Ministerio de Educacion de Chile (MINEDUC), Universidad de Tarapao (UTA)
- Flemish Institute for Technological Research (VITO), Belgium
- National Centre for the Replacement, Refinement and Reduction (NC3Rs) of animals in research [NC.K500045.1, G0800697]
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Japan Science and Technology Agency
- JST, CREST
- Ministry of Science and Technology of Taiwan [NSC93-2314-B-320-006, NSC94-2314-B-320-002]
- National Research Foundation of Korea (NRF) of the Ministry of Education, Science and Technology [2012R1A2A2A01010870]
- Ministry of Health and Welfare, Republic of Korea [HI13C1449]
- UAMS/NIH Clinical and Translational Science Award [UL1TR000039, KL2TR000063]
- Arkansas Biosciences Institute
- Czech Science Foundation [13-07711S]
- NIH [CA116812]
- National Institute of Environmental Health Sciences [ES016893]
- Maine Center for Toxicology and Environmental Health
- FERO Foundation in Barcelona, Spain
- Cancer Research UK
- International Journal of Experimental Pathology
- Swim Across America Cancer Research Award
- American Cancer Society [116683-RSG-09-087-01-TBE]
- Fund for Scientific Research-Flanders (FWO-Vlaanderen)
- Inter University Attraction Pole grant [IAP-P7-07]
- Miguel Servet Research Contract Program [CP10/00656]
- Taipei Medical University [TMU101-AE3-Y19]
- Genesis Oncology Trust (NZ) Professional Development Grant
- Faculty of Medicine, University of Otago, Dunedin, New Zealand
- Dutch Cancer Society [UVA2011-4969]
- AICR [14-1164]
- Breast Cancer Research Program [W81XWH-14-1-0087]
- Department of Science and Technology, Government of India [SR/FT/LS-063/2008]
- NIEHS contracts [N01-ES 35504, HHSN27320140003C]
- King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia [T.K. 11-0629]
- Dalhousie Medical Research Foundation
- Beatrice Hunter Cancer Institute
- CIHR
- Nova Scotia Lung Association
- PHS grants from the NIH [R01-CA141704, R01-CA150214, R01-DK52825, R01-CA61774]
- Charles University in Prague [UNCE 204015, PRVOUK P31/2012]
- Health and Medical Research Fund of Food and Health Bureau, Hong Kong Special Administrative Region [10110021]
- [PI12/01104]
- [CP03/00101]
- ICREA Funding Source: Custom
- National Research Foundation of Korea [2010-0018545, 2013M2B2A9A03051296] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- Div Of Information & Intelligent Systems
- Direct For Computer & Info Scie & Enginr [1218712] Funding Source: National Science Foundation
- Medical Research Council [MR/L007215/1] Funding Source: researchfish
- Natural Environment Research Council [ceh010010] Funding Source: researchfish
- MRC [MR/L007215/1] Funding Source: UKRI
Ask authors/readers for more resources
Low-dose exposures to common environmental chemicals that are deemed safe individually may be combining to instigate carcinogenesis, thereby contributing to the incidence of cancer. This risk may be overlooked by current regulatory practices and needs to be vigorously investigated.Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.
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