Cancer is a Genetically Modified Organism Hypothesis

Mini Review

Austin J Med Oncol. 2016; 3(1): 1029.

Cancer is a Genetically Modified Organism Hypothesis

Chan JCY*

33 Magnus Street, Nelson Bay NSW, Australia

*Corresponding author: John Cheung Yuen Chan, 33 Magnus Street, Nelson Bay NSW, Australia

Received: November 01, 2016; Accepted: December 02, 2016; Published: December 05, 2016

Abstract

During DNA replication, if the DNA strand breaks, such as a Double Strand Break (DSB), either the exogenous viruses or endogenous viral relics may be incorporated into the newly replicated cell. The new cell is a Genetically Modified Organism (GMO) due to these viral genes. The GMO cell will express the trait of the gene which it arose from, known as proliferation, a trait of the unicellular organism. The new genetically engineered cell is a viral gene cancer (VGC). It flouts the normal cell’s standard rules of growth and it has a chaotic DNA replication. The other viral genes may be integrated into the new cell by Horizontal Gene Transfer (HGT).

As the cancer progresses further, the ancient genes which were deeply imbedded into the mammalian genome may be incorporated into new GMOs by HGT. The new cell, an Ancient Gene Cancer (AGC), would express the traits of the genes from which it arose. Its traits are proliferation, lost adhesiveness and stiffness, and anaerobic metabolism. This is because the ancient eukaryotic cells lived in water and in a hypoxic environment. The AGC could break off from the tumour and enter the blood vessel because of the lack of the cell’s adhesiveness. With less stiffness, the AGC could deform itself and squeeze through a tiny intercellular gap. This is the reason the AGC could metastasize into other organs.

Keywords: Viral gene cancer; Ancient gene cancer; Hallmarks of cancer; Cancer is GMO; Cancer hypothesis; Cancer theory

Abbreviations

DSB: Double Strand Break; GOE: Great Oxygenation Event; HGT: Horizontal Gene Transfer; GMO: Genetically Modified Organism; VGC: Viral Gene Cancer; AGC: Ancient Gene Cancer; ERV: Endogenous Retroviruses

Evolutionary Background

The early life of Earth consisted of viruses, bacteria, prokaryotes and eukaryotes, etc., which emerged during this primordial time. There were many genes exchanged among these unicellular organisms. These unicellular organisms were selfish [1]. No free oxygen existed in early Earth time until about 2.7 billion years ago when cyanobacteria began producing oxygen and glucose by photosynthesis. Any oxygen they produced was chemically captured by dissolved iron or organic matter. The eukaryotic cells lived in water in a hypoxic environment and metabolized glucose by fermentation. These organisms were unable to live on land because there was no ozone layer protection from the Sun’s ultraviolet radiation. These anaerobic metabolism organisms lived in a harsh environment and they have stronger innate immunity. The Great Oxygenation Event (GOE) happened about a half-a-billion years ago when the oxygen sinks became saturated.

Many new species evolved after the GOE with aerobic metabolism. Aerobic metabolism is 19 times more efficient than anaerobic metabolism; therefore more complex species evolved and created biological diversification. The anaerobic metabolism organisms were either massively extinguished or evolved into aerobic metabolism organisms. Viruses have invaded mammals or their ancestors, and viral genetic relics have been left in the host’s genome. The mammalian genome has both genetic relics of aerobic metabolism viruses and ancient eukaryotes genes.

DNA Replication

There are roughly 32.7 trillion cells in the average adult human body. If the mammalian cell becomes old or damaged, the cell is replaced by replicated cells. During each cell division, more than 3.3 billion base pairs of genomic DNA have to be duplicated. Defects can possibly arise when DNA is copied during cell division. There would be disastrous consequences if sufficient defects were accumulated. Therefore the normal cells have a finite number of replications, referenced by shortening the telomeres, in order to avoid a possible unmanageable quantity of mutations being accumulated. In Khoronenkova’s study, about 10 to 20 thousand endogenous DNA Single-Strand Breaks (SSB) form per day and 10-20 DNA Double- Strand Breaks (DSB) are formed during this period. These errors could lead to disease, including cancer [2].

Repair of the Defective Cell

Elephants have a 100 times more cells than humans, yet their cancer mortality rate is less than 5 percent compared to 11 to 25 percent in humans. In the African elephant genome there are at least 40 copies of genes that code for protein p53 compared to only the two found in humans. Elephants increase their apoptotic response following DNA damage, rather than relying on the immune system to mop up the defective cells after the cell is replicated [3]. In Abrams study, the normal p53 gene action restrains transposons that can make copies of themselves and move to different positions on chromosomes [4]. The Nobel Prize in Chemistry 2015 was awarded to three pioneering scientists of DNA repair. Tomas Lindahl demonstrated base excision repair, which constantly counteracts the collapse of our DNA. Aziz Sancar has mapped nucleotide excision repair. Paul Modrich has demonstrated mismatch repair, reducing the error frequency during DNA replication by about a thousand-fold [5].

Defective cells evade eradication by checkpoints

Mammals may ignore the cancer cells and think they are nonforeign cells. Some examples are as follows:

Cancer is GMO

What is the origin of cancer? It is an interesting question. If about 10% to 20% of cancers originate from exogenous viruses, then where does the other 80% to 90% of cancers originate?

We observe two phenomena:

Normally, the GMO is a process of manually incorporating new genes into an organism to create one or more traits that are not already found in that organism. In cancer development, whether a gene was from exogenous viral genes or endogenous dormant genetic relics which are incorporated into the recipient cell by HGT, the GMO will express the traits of the genes from which it arose. The main trait is proliferation which is a typical unicellular organism trait.

If a virus invades the mammal cell, such as HPV, the virus resides inside the mammalian cell and relies on that cell to provide nutrients. If the DNA replication is faulty, such as a DSB, the repair may pick the genes near the point of the break and attach them to where it is broken. However, if the picked up genes are from exogenous viruses or endogenous viral genetic relics, then it has the virus’s traits and the new GMO is a viral gene cancer (VGC). After the viral gene cancer develops, it flouts the normal cell’s standard rules of growth. The other viral genetic relics could be incorporated into a new GMO by HGT. The new GMO will express all viral gene traits and its proliferation. The GMO could mutate to adapt to the microenvironment as well. This is one reason why cancer patient’s cancer genomes are not the same.

Exogenous viral gene GMO

If the normal cell has viruses inside its cell and DNA breakage occurs, such as a cervical cell infected with the HPV virus, the new DNA may pick up the genes from the HPV virus and incorporate them into the new cell (HPV viral genes inserted into new DNA). This new cell is a GMO genetically engineered from HPV genes by HGT. The HPV vaccine would eliminate the effective HPV viruses, and hence reduce the possibility of HPV genetically engineering the new cells if the DNA replication is faulty, thereby reducing the possibility of cervical cancer.

Endogenous viral gene GMO

The viral genetic relics inside the cell are mostly dormant and provide limited function. If the viral genetic relics are incorporated into a new cell such as the GMO, the new cell will express the trait of the viral genes it arose from. Humans have about 8% retroviruses and other types of viral genetic relics in their genome.

Link between viruses and viral gene cancers

The new GMO will express the trait of viruses which is proliferation. With the following observations:

Viral Gene Cancer Treatment Strategy

Chemotherapy

The immune system may not be able to handle large tumour burden loads. Thus we need to reduce tumour burden to give the immune system a chance to eradicate the remaining tumour. This approach is similar to a severe bacterial infection requiring antibacterial treatment. The normal cancer therapies are surgery, radiation or chemotherapy. Unfortunately the maximum tolerated dosage of chemotherapy could damage the immune system which is desperately needed to eradicate the remaining tumours. It is a challenge to find alternative therapeutic options which would reduce tumour burden and not dampen the immune system. There are some possibilities to explore:

Immunotherapy

In necrotic cell death, cells undergoing necroptosis rupture and leak their contents into the intercellular space. I envisage that all the above therapies could kill some tumours. The dead cancer cell acts as an antigen and the immune system could create antibodies in response to it.

Ancient Eukaryotic Gene GMO

The mammalian genome was evolved from anaerobic eukaryotes rather than starting from afresh after the GOE. The ancient genes are deeply imbedded in the mammalian genome. The ancient genes are fewer in quantity in comparison with viral genetic relics in the genome. If the viral gene tumour developed further, as the cells have chaotic replication, then ancient genes with anaerobic metabolism could be incorporated into new GMO cells such as the Ancient Gene Cancer (AGC). The AGC would express the traits of an ancient eukaryotic organism (Table 1).

Citation: Chan JCY. Cancer is a Genetically Modified Organism Hypothesis. Austin J Med Oncol. 2016; 3(1): 1029. ISSN:2471-027X