Preprint Review Version 3 Preserved in Portico This version is not peer-reviewed

Biochemistry, Not Oncogenes, may Demystify and Defeat Cancer

Version 1 : Received: 19 April 2021 / Approved: 22 April 2021 / Online: 22 April 2021 (09:37:10 CEST)
Version 2 : Received: 4 July 2021 / Approved: 6 July 2021 / Online: 6 July 2021 (11:32:47 CEST)
Version 3 : Received: 27 December 2021 / Approved: 28 December 2021 / Online: 28 December 2021 (10:53:54 CET)

How to cite: Kulsh, J. Biochemistry, Not Oncogenes, may Demystify and Defeat Cancer. Preprints 2021, 2021040602 (doi: 10.20944/preprints202104.0602.v3). Kulsh, J. Biochemistry, Not Oncogenes, may Demystify and Defeat Cancer. Preprints 2021, 2021040602 (doi: 10.20944/preprints202104.0602.v3).


The presence of mutated genes strongly correlates with the incidence of cancer. Decades of research, however, has not yielded any specific causative gene or set of genes for the vast majority of cancers. The Cancer Genome Atlas program was supposed to provide clarity but it only gave much more data without any accompanying insight into how the disease begins and progresses. It may be time to notice that epidemiological studies consistently show that the environment, not genes, has the principal role in causing cancer. Since carcinogenic chemicals in our food, drink, air and water are the primary culprits, we need to look at the biochemistry of cancer, with a focus on enzymes which invariably facilitate transformations in a cell. In particular, attention should be paid to the rate-limiting enzyme in DNA synthesis, ribonucleotide reductase (RnR) whose activity is tightly linked to tumor growth. Besides circumstantial evidence that cancer is induced at this enzyme’s vulnerable free-radical-containing active-site by various carcinogens, its role in initiating retinoblastoma and HPV-related cervical cancers is well documented. Blocking the activity of malignant RnR is a certain way to arrest cancer.


carcinogenesis; cancer treatment; cervical cancer; DNA synthesis; free-radical; retinoblastoma; ribonucleotide reductase; somatic mutation theory (SMT)


MEDICINE & PHARMACOLOGY, Oncology & Oncogenics

Comments (1)

Comment 1
Received: 28 December 2021
Commenter: Jay Kulsh
Commenter's Conflict of Interests: Author
Comment: This is 2nd and probably the last revision of the article:
- The first section now has the word “Introduction” in its title, with a small extra paragraph – and a new section “Conclusions” has been added at the end.
- “2.3.1 The Cancer Genome Atlas (TCGA) program” section has been shifted down, but at a higher level, so it is now numbered 2.5.
- A sub-sub-section “4.1.1 Re-evaluating chemical structure of a compound for carcinogenicity” has been added.
- “5. Disabling ribonucleotide reductase will defeat cancer” section has been expanded with a specific example.
- A figure has been added in section 4.
- About twenty references have been added, because of above expansions, and to buttress the assertions in the article.
- English has been checked/corrected by a professional company.
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