Review
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Immunol. Jul 27, 2017; 7(2): 11-23
Published online Jul 27, 2017. doi: 10.5411/wji.v7.i2.11
Holistic paradigm in carcinogenesis: Genetics, epigenetics, immunity, inflammation and oral infections
Sok-Ja Janket, Marium Qureshi, Antonio Bascones-Martinez, Jerian González-Febles, Jukka H Meurman
Sok-Ja Janket, Department of Periodontology, Boston University H. M. Goldman School of Dental Medicine, Boston, MA 02118, United States
Sok-Ja Janket, Marium Qureshi, Department of General Dentistry, Boston University H. M. Goldman School of Dental Medicine, Boston, MA 02118, United States
Antonio Bascones-Martinez, Jerian González-Febles, Department of Oral Medicine and Surgery, Complutense University, 28040 Madrid, Spain
Jukka H Meurman, Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, 02160 Helsinki, Finland
Author contributions: All authors contributed to this paper.
Supported by Helsinki University Hospital funds, No. TYH2015323 (to Meurman JH).
Conflict-of-interest statement: The authors declare no conflict of interest associated with this paper.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Sok-Ja Janket, DMD, MPH, Department of Periodontology, Boston University H. M. Goldman School of Dental Medicine, 100 East Newton Street, Room B08A, Boston, MA 02118, United States. skjanket@bu.edu
Telephone: +1-617-4141066 Fax: +1-617-4141061
Received: January 8, 2017
Peer-review started: January 12, 2017
First decision: February 16, 2017
Revised: February 25, 2017
Accepted: April 4, 2017
Article in press: April 7, 2017
Published online: July 27, 2017
Processing time: 199 Days and 18.4 Hours
Abstract

Recent debate among the experts of cancer research regarding the main causes of carcinogenesis encouraged us to review the etiology of cancer pathogenesis. The somatic mutation theory attributes carcinogenesis to random errors in DNA multiplication while the tissue organization field theory ascribes causation to environmental factors. We recognize complexity in cancer pathogenesis and accept the premise of both DNA multiplication errors and environmental factors in cancer development. Furthermore, it should also be noted that the combination of these factors and the relative importance of the each differ in various types of cancers. For example, in some cancers, genetics plays a prominent role while in others environment such as obesity plays a much stronger role. Additionally, the cancer mitigating factors should also be considered. The balance of cancer-enhancing and cancer-suppressing forces determines the cancer incidence. Ultimately, identifying the lifestyle factors that revise somatic mutations or epigenetic alterations will lead to a clear understanding of pathogenic mechanisms of cancer and to the optimal preventive strategies. This narrative review evaluates the published evidence on carcinogenesis pertaining to the whole organism (thus, holistic) incorporating genetics, epigenetics, immunology, inflammation and infections with emphasis on oral infections.

Keywords: Genetics; Carcinogenesis; Inflammation; Epigenetics; Immunity; Infections

Core tip: A recent debate among renowned scholars prompted us to review cancer pathogenesis in a holistic approach. One group attributed cancer to “random errors in DNA multiplication” (Tomasetti C, Science, 2015) while other experts credited environmental factors for cancer causation (Wu S, Nature, 2016). However, we put forward the concept that cancer is multifactorial and both intrinsic (DNA multiplication errors) and extrinsic (environmental) factors contribute to carcinogenesis. In this review, we examined these risk factors in some detail covering genetics, epigenetics, immunity, inflammation and infections. We acknowledge the contribution of each risk factor is different in various types of cancer. In some cancers, genetics plays a powerful role while in others, metabolism contributes a stronger impact. Therefore, a holistic understanding of carcinogenesis is truly necessary considering multisystem involvement in cancer development.