title: Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition.
abstract: Genomic instability can initiate cancer, augment progression, and influence the overall prognosis of the affected patient. Genomic instability arises from many different pathways, such as telomere damage, centrosome amplification, epigenetic modifications, and DNA damage from endogenous and exogenous sources, and can be perpetuating, or limiting, through the induction of mutations or aneuploidy, both enabling and catastrophic. Many cancer treatments induce DNA damage to impair cell division on a global scale but it is accepted that personalized treatments, those that are tailored to the particular patient and type of cancer, must also be developed. In this review, we detail the mechanisms from which genomic instability arises and can lead to cancer, as well as treatments and measures that prevent genomic instability or take advantage of the cellular defects caused by genomic instability. In particular, we identify and discuss five priority targets against genomic instability: (1) prevention of DNA damage; (2) enhancement of DNA repair; (3) targeting deficient DNA repair; (4) impairing centrosome clustering; and, (5) inhibition of telomerase activity. Moreover, we highlight vitamin D and B, selenium, carotenoids, PARP inhibitors, resveratrol, and isothiocyanates as priority approaches against genomic instability. The prioritized target sites and approaches were cross validated to identify potential synergistic effects on a number of important areas of cancer biology.
authors: Discipline of Nutrition, University of Auckland, Auckland, New Zealand. Electronic address: l.ferguson@auckland.ac.nz.
authors: Lynnette R
authors: LR
authors: Ferguson
authors: Department of Pediatrics, University of British Columbia, Michael Cuccione Childhood Cancer Research Program, Child and Family Research Institute, Vancouver, Canada.
authors: Helen
authors: H
authors: Chen
authors: Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors: Andrew R
authors: AR
authors: Collins
authors: Department of Pediatrics, University of British Columbia, Michael Cuccione Childhood Cancer Research Program, Child and Family Research Institute, Vancouver, Canada.
authors: Marisa
authors: M
authors: Connell
authors: Department of Oncology, Instituti di Ricovero e Cura a Carattere Scientifico-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors: Giovanna
authors: G
authors: Damia
authors: Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, United States.
authors: Santanu
authors: S
authors: Dasgupta
authors: School of Pharmacy, University College Cork, Cork, Ireland.
authors: Meenakshi
authors: M
authors: Malhotra
authors: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States.
authors: Alan K
authors: AK
authors: Meeker
authors: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors: Amedeo
authors: A
authors: Amedei
authors: Department of Biology, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates; Faculty of Science, Cairo University, Cairo, Egypt.
authors: Amr
authors: A
authors: Amin
authors: Department of Chemistry, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates.
authors: S Salman
authors: SS
authors: Ashraf
authors: Department of Biology, Università di Roma Tor Vergata, Rome, Italy.
authors: Katia
authors: K
authors: Aquilano
authors: Department of Biology, University of Rochester, Rochester, United States.
authors: Asfar S
authors: AS
authors: Azmi
authors: School of Chemical and BioTechnology, SASTRA University, Thanjavur, Tamil Nadu, India.
authors: Dipita
authors: D
authors: Bhakta
authors: Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.
authors: Alan
authors: A
authors: Bilsland
authors: Department of BioMedical Sciences, Creighton University, Omaha, NE, United States.
authors: Chandra S
authors: CS
authors: Boosani
authors: Department of Research & Development, Ovarian and Prostate Cancer Research Trust Laboratory, Guildford, Surrey, United Kingdom.
authors: Sophie
authors: S
authors: Chen
authors: Department of Biology, Università di Roma Tor Vergata, Rome, Italy.
authors: Maria Rosa
authors: MR
authors: Ciriolo
authors: Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Nara, Japan.
authors: Hiromasa
authors: H
authors: Fujii
authors: School of Chemical and BioTechnology, SASTRA University, Thanjavur, Tamil Nadu, India.
authors: Gunjan
authors: G
authors: Guha
authors: New York Medical College, Valhalla, NY, United States.
authors: Dorota
authors: D
authors: Halicka
authors: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Champaign, IL, United States.
authors: William G
authors: WG
authors: Helferich
authors: Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.
authors: W Nicol
authors: WN
authors: Keith
authors: Department of Comparative Pathobiology and Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN, United States.
authors: Sulma I
authors: SI
authors: Mohammed
authors: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors: Elena
authors: E
authors: Niccolai
authors: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Champaign, IL, United States.
authors: Xujuan
authors: X
authors: Yang
authors: Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Nara, Japan.
authors: Kanya
authors: K
authors: Honoki
authors: Discipline of Nutrition, University of Auckland, Auckland, New Zealand.
authors: Virginia R
authors: VR
authors: Parslow
authors: School of Pharmacy, University College Cork, Cork, Ireland.
authors: Satya
authors: S
authors: Prakash
authors: Department of Biology, University of Rochester, Rochester, United States.
authors: Sarallah
authors: S
authors: Rezazadeh
authors: Department of Pathology, Louisiana State University Health Shreveport, Shreveport, LA, United States.
authors: Rodney E
authors: RE
authors: Shackelford
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
authors: David
authors: D
authors: Sidransky
authors: Departments of Radiation Oncology & Molecular Radiation Sciences, Oncology and Urology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, United States.
authors: Phuoc T
authors: PT
authors: Tran
authors: Department of Radiation Oncology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, United States.
authors: Eddy S
authors: ES
authors: Yang
authors: Department of Pediatrics, University of British Columbia, Michael Cuccione Childhood Cancer Research Program, Child and Family Research Institute, Vancouver, Canada. Electronic address: cmaxwell@cfri.ca.
authors: Christopher A
authors: CA
authors: Maxwell
mesh_terms: D018385:Centrosome / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004032:Diet; D042822:Genomic Instability / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000178:diet therapy* / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D019098:Telomerase
keywords: Cancer prevention; Cancer therapy; DNA damage; Genomic instability; Nutraceutical