Igor Tadić

02. November 2018.

Cancer Cause And

Prevention

Abstract

It is well researched that there is a direct connection between inflammatory reactions in body and
tumor growth. In this article we will collect all the evidence and data behind mechanisms driving
the increased tumor growth rates in recent decades with the goal of informing the public and the
world of medicine of actual causes of cancer and their possible ways of prevention.

Introduction

Cancer has major impact on society across the world. Cancer is among the leading causes of death
worldwide. In 2012. there were 14.1 million new cases and 8.2 million cancer related deaths world
wide. The number of new cancer cases per year is expected to rise to 23.6 million by 2030.
In medicine, cause of cancer is deemed mostly unknown. Although, there is a lot of data showing
that healthy life choices, be it athletic activity and correct dietary choices or directly avoiding
cancer-inducing factors such as smoking or pollution. The big part of what causes and what cures
cancer and tumor growth is a medical mystery, but we are forced to hypothesize.

Inflammation and DNA damage

Several lines of evidence suggest that DNA-damage especially the one resistant to repair can cause
immune reaction and inflammation, and is linked to cancer development and other pathologies.
On the other hand, it is generally accepted that chronic inflammation can cause DNA persistent
damage and act as a driver for pathophysiological phenotypes like cancer.
in the review article of Spanou et al. the role of genetic variability as a regulator of TLR4 and NOD
signaling in response to bacterial driven DNA Damage Response (DDR) and Inflammation is
discussed with a focus on the gastrointestinal (GI) Tract.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650959/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578195/
Igor Tadić
02. November 2018.

Source

Under inflammatory conditions, nitric oxide (NO) is generated in inflammatory and epithelial cells,
and this reaction is catalyzed by NO synthase (NOS), especially inducible nitric oxide synthase
(iNOS). NO and NOS are known to play roles on both pro- and anti-carcinogenic effects [8].
Sustained induction of iNOS in chronic inflammation can produce ROS and RNS, causing DNA
damage. NO reacts with superoxide (O 2−) to form peroxynitrite (ONOO −), which causes
guanine nitration to generate 8-nitroguanine. 8-Nitroguanine is a mutagenic DNA damage.
The glycosidic bond between 8-nitroguanine and deoxyribose in DNA strand is
thermodynamically unstable. Therefore, 8-nitroguanine can be spontaneously released,
leading to the formation of an apurinic site. Adenine can be incorporated opposite the
apurinic site during DNA synthesis according to the A-rule. Translesion DNA synthesis,
which bypasses apurinic sites, is mediated by DNA polymerase ζ subunits, Rev1 and
Rev3. 8-Nitroguanine can form a pair with adenine during DNA synthesis, and this
process is catalyzed by polymerase η and a truncated form of polymerase K.These
suggest that 8-nitroguanine formation leads to single base substitutions, particularly G:C to
T:A transversions.
−
NO and O2 are released from neutrophils or macrophages during inflammation. NO is
long-lived enough to diffuse through the extracellular matrix, cross the plasma membrane
and the cytoplasm of epithelial cells, and enter the nucleus, whereas O 2− is not
sufficiently long-lived to react with DNA in the nucleus of epithelial cells. Alternatively,
inflammatory cells may release cytokines including tumor necrosis factor α (TNF- α) to
stimulate O2− accumulation in neighboring epithelial cells. Relevantly, it was reported that
interaction of TNF- α and TNF receptor 1 promotes gastric tumorigenesis via the induction
of NAD(P)H oxidase (Nox) in tumor cells. Nox generates O 2− in cancer cells. NO,.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650959/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578195/
Igor Tadić
02. November 2018.

which is generated by iNOS in tumor-associated macrophage (TAM), reacts with O 2− in

cancer cells, forming ONOO −. ONOO − causes DNA damage, mutation and genomic
instability to proceed tumor malignancy

Source

Conclusion

It is natural to conclude that inflammatory stress on DNA is the leading

mechanism behind mutation of cells and growth of cancers. If this shows to
be true than lowering body inflammation could lead to decreased rates of
cancerogenic cells in people who are genetically prone to their production.
Further, it leads us to believe that most cancers start in the gut, where the
bacteria controls the production of hormones that drive DNA damage.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650959/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578195/