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Somatic Mutation Theory – Why it’s Wrong for Most Cancers

May 3, 2016 by 2012pharmaceutical

Somatic Mutation Theory – Why it’s Wrong for Most Cancers

Reporter: Aviva Lev-Ari, PhD, RN

Somatic Mutation Theory – Why it’s Wrong for Most Cancers.

Cell Physiol Biochem 2016;38:1663-1680. http://www.karger.com/Article/FullText/443106

Björn L.D.M. Brücher and Ijaz S. Jamall

Brucher [a to d] and Jamall [a,b,e]

a Theodor-Billroth-Academy®, Munich, Germany – Sacramento, California, USA;

b INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy®, Munich, Germany – Sacramento, California, USA;

c Bon Secours Cancer Institute, Richmond, VA, USA;

d Dep. of Surgery, Carl- Thiem-Klinikum, Cottbus, Germany;

e Risk-Based Decisions Inc., Sacramento, CA, USA

Key Words

Carcinogenesis • Somatic mutation theory • Microenvironment • Cell communication • Signaling • Inflammation • Chronic inflammation • Fibrosis • Cell transition • Precancerous niche

Abstract

Hysteron proteron reverses both temporal and logical order and this syllogism occurs in carcinogenesis and the somatic mutation theory (SMT): the first (somatic mutation) occurs only after the second (onset of cancer) and, therefore, observed somatic mutations in most cancers appear well after the early cues of carcinogenesis are in place. It is no accident that mutations are increasingly being questioned as the causal event in the origin of the vast majority of cancers as clinical data show little support for this theory when compared against the metrics of patient outcomes. Ever since the discovery of the double helical structure of DNA, virtually all chronic diseases came to be viewed as causally linked to one degree or another to mutations, even though we now know that genes are not simply blueprints, but rather an assemblage of alphabets that can, under non-genetic influences, be used to assemble a business letter or a work of Shakespearean literature. A minority of all cancers is indeed caused by mutations but the SMT has been applied to all cancers, and even to chemical carcinogenesis, in the absence of hard evidence of causality. Herein, we review the 100 year story of SMT and aspects that show why genes are not just blueprints, how radiation and mutation are associated in a more nuanced view, the proposed risk of cancer and bad luck, and the in vitro and in vivo evidence for a new cancer paradigm. This paradigm is scientifically applicable for the majority of non-heritable cancers and consists of a six-step sequence for the origin of cancer. This new cancer paradigm proclaims that somatic mutations are epiphenomena or later events occurring after carcinogenesis is already underway. This serves not just as a plausible alternative to SMT and explains the origin of the majority of cancers, but also provides opportunities for early interventions and prevention of the onset of cancer as a disease.

Conclusions

The incorrect interpretation of data can sometimes appear to be the more parsimonious explanation especially when it has acquired the mantle of a paradigm, as in the case of the SMT. Summa Cancerologica is not hypothetical or ontological. Its syllogism of carcinogenesis needs the consideration of all reasonable perspectives such as whether somatic mutations are later events or epiphenomena occurring at the end of the sequence of events in carcinogenesis. This mutatio praemissarum leads to a reflection of reasoned judgments of correct findings in cancer (mutations within tumors) together with clinical observations (relevance of such mutations to cancer therapy). An overemphasis of the SMT as the sole reason of the origin of carcinogenesis elevated it to the status of a dogma which downplays significant findings of mutations and genetics in different fields of nature, biology and science. However, there is hope that hereditary cancers can be treated in the near future as new technologies make it possible to manipulate proteins packaging DNA to turn on specific gene promoters and enhancers [164]. If this were applicable to the mass of non-hereditary cancers this approach would still be only symptomatic as the genesis of non-hereditary cancers is not caused by somatic mutations though somatic mutations occur within tumors. Focusing on the tumor cell without its origin including the microenvironment won’t be enough [165]. The reasoning on the origin of carcinogenesis, including different step-wise sequences, may help unmask mechanisms of the transition of a normal into a cancer cell (cancer genesis) as well as its different primary pathogenic stimulus, which can serve to prevent or retard cancers instead of concentrating on symptomatic strategies or for a cure for all cancers. It is scientifically valid based on in vitro and in vivo genetic findings that carcinogenesis consists of a six-step multi sequence process [17, 18]. This serves not just as a plausible alternative to the SMT to explain the origin of the majority of cancers, but could also suggest early interventions and thereby prevent the onset of cancer as a disease.

FULL ARTICLE

2016-CELL-PHYSIOL-BIOCHEM-Somatic-Mutation-Theory