@article{9e0abe15594b41cf8da9aaa282ce04cd,
title = "Tumour predisposition and cancer syndromes as models to study gene–environment interactions",
abstract = "Cell division and organismal development are exquisitely orchestrated and regulated processes. The dysregulation of the molecular mechanisms underlying these processes may cause cancer, a consequence of cell-intrinsic and/or cell-extrinsic events. Cellular DNA can be damaged by spontaneous hydrolysis, reactive oxygen species, aberrant cellular metabolism or other perturbations that cause DNA damage. Moreover, several environmental factors may damage the DNA, alter cellular metabolism or affect the ability of cells to interact with their microenvironment. While some environmental factors are well established as carcinogens, there remains a large knowledge gap of others owing to the difficulty in identifying them because of the typically long interval between carcinogen exposure and cancer diagnosis. DNA damage increases in cells harbouring mutations that impair their ability to correctly repair the DNA. Tumour predisposition syndromes in which cancers arise at an accelerated rate and in different organs — the equivalent of a sensitized background — provide a unique opportunity to examine how gene–environment interactions influence cancer risk when the initiating genetic defect responsible for malignancy is known. Understanding the molecular processes that are altered by specific germline mutations, environmental exposures and related mechanisms that promote cancer will allow the design of novel and effective preventive and therapeutic strategies.",
author = "Michele Carbone and Arron, {Sarah T.} and Bruce Beutler and Angela Bononi and Webster Cavenee and Cleaver, {James E.} and Croce, {Carlo M.} and Alan D{\textquoteright}Andrea and Foulkes, {William D.} and Giovanni Gaudino and Groden, {Joanna L.} and Henske, {Elizabeth P.} and Hickson, {Ian D.} and Hwang, {Paul M.} and Kolodner, {Richard D.} and Mak, {Tak W.} and David Malkin and Monnat, {Raymond J.} and Flavia Novelli and Pass, {Harvey I.} and Petrini, {John H.} and Schmidt, {Laura S.} and Haining Yang",
note = "Funding Information: M.C. and H.Y. report funding from the US National Institute of Environmental Health Sciences (1R01ES030948-01 (M.C and H.Y.)), the US National Cancer Institute (1R01CA237235-01A1 (M.C. and H.Y.) and 1R01CA198138 (M.C.)), the US Department of Defense (CA150671 (M.C. and H.Y.)) and the University of Hawai{\textquoteright}i Foundation through donations from Riviera United-4 a Cure (M.C. and H.Y.), the Melohn Family Endowment, Honeywell International Inc., the Germaine Hope Brennan Foundation and the Maurice and Joanna Sullivan Family Foundation (M.C.). M.C. has a patent issued entitled {\textquoteleft}Methods for diagnosing a predisposition to develop cancer{\textquoteright}. M.C. and H.Y. have a patent issued entitled {\textquoteleft}Using anti-HMGB1 monoclonal antibody or other HMGB1 antibodies as a novel mesothelioma therapeutic strategy{\textquoteright} and a patent issued entitled {\textquoteleft}HMGB1 as a biomarker for asbestos exposure and mesothelioma early detection{\textquoteright}. M.C. is a board-certified pathologist who provides consultation for pleural pathology, including medical–legal consultation. A.D. Funding Information: receives research funding from Eli Lilly and Merck KGaA (EMD Serono), has served on advisory boards for Eli Lilly, Merck KGaA (EMD Serono), Sierra Oncology, Intellia and Formation Biologics and holds equity in Ideaya Inc., Cyteir Therapeutics and Cedilla Therapeutics Inc. I.D.H. is supported by the Danish National Research Foundation (grant no. DNRF115) and by the Nordea Foundation. R.J.M. is supported by grants from the US National Cancer Institute, the US National Heart, Lung and Blood Institute and the Fanconi Anemia Research Fund.. The work of R.J.M. is funded by US National Institutes of Health award NCI P01 077852 and by research awards from the Fanconi Anemia Research Fund and the US Department of Defense Bone Marrow Failure Program. R.J.M. holds equity in bluebird bio and has performed consulting work for Flagship Pioneering. H.I.P. reports funding from the US National Cancer Institute, the US Department of Defense, the US Centers for Disease Control and Prevention, Genentech, and Belluck & Fox. R.D.K. received research support from the US National Institutes of Health (GM26017 and GM50006) and the Ludwig Institute for Cancer Research. He is an inventor on patents covering many aspects of mismatch repair genes, all of which are assigned to the Dana-Farber Cancer Institute. L.S.S. reports funding in part through US federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN261200800001E. J.H.P. is supported by US National Institute of General Medical Science and US National Cancer Institute grants and the Memorial Sloan-Kettering Cancer Center Core Grant P30 CA008748, licenses reagents through Novus Biologicals and is a consultant for ATROPOS Therapeutics. H.I.P and H.Y. received research support for the Early Detection Research Network, US National Cancer Institute (U01CA111295-08). S.T.A., B.B., A.B., W.C., J.E.C., C.M.C., W.D.F., G.G., J.L.G., E.P.H., P.M.H., T.W.M., D.M. and F.N., declare no competing interests. Funding Information: Funding for travel costs and lodging for the co-authors to meet in person and critically discuss and write the manuscript was provided by a generous donation from the Barry and Virginia Weinman Foundation. Publisher Copyright: {\textcopyright} 2020, Springer Nature Limited.",
year = "2020",
month = sep,
day = "1",
doi = "10.1038/s41568-020-0265-y",
language = "English (US)",
volume = "20",
pages = "533--549",
journal = "Nature Reviews Cancer",
issn = "1474-175X",
publisher = "Nature Publishing Group",
number = "9",
}