For decades, cancer has been framed as a genetic disease. This belief has driven most of our research—the annual spending on genetic research, through the National Cancer Institute (NCI), is estimated to be around $7.8 billion in the United States every year. Despite these efforts, not a single gene has been definitively proven to cause cancer independently, and no effective therapies have been developed.
The widely accepted view of cancer proposes that it begins with a single mutated cell, a concept referred to as clonality. According to this perspective, a genetic mutation disrupts the normal regulatory mechanisms within a cell, allowing it to multiply uncontrollably and form a clonal population of identical cancerous cells.
This idea serves as the cornerstone of the Somatic Mutation Theory (SMT), which suggests that the accumulation of additional mutations over time drives the progression from a single abnormal cell to a fully malignant tumor.
Mainstream thinking / the SMT suggests that:
- Mutations drive cancer progression. A single genetic mutation in a critical gene, such as an oncogene or tumor suppressor gene, can initiate uncontrolled cell growth. For instance, a mutation in the tumor suppressor gene TP53 can impair its ability to regulate the cell cycle and apoptosis, allowing damaged cells to survive and proliferate.
- Cancer develops through a series of genetic changes. Multiple mutations accumulate over time, driving the progression from a normal cell to a malignant one. Each mutation confers a selective advantage, enabling cancer cells to proliferate.
- Clonal expansion is central to tumor formation. Once a single cell acquires a significant mutation, it divides and produces a population of genetically identical cells (a clone). Additional mutations within this clonal population drive tumor heterogeneity and aggressive behavior.
Because this is the prevailing theory, the genetic code is the primary target in cancer research. Although the SMT remains the predominant explanation for cancer development, it is consistently challenged.
Despite decades of intensive research, not a single gene has been definitively identified as the sole cause of cancer. Mutations in certain genes, such as TP53 or BRCA1, are strongly associated with cancer, but they are not sufficient on their own to drive malignancy. Many individuals carry mutations in these “cancer-associated genes” without ever developing the disease. This suggests that genes alone are insufficient to cause cancer.
“Oncological pathologists, looking at slices of a tumor, believe they can guess when the cells have an evil intention. However, biologists studying living cells find that cells can do only what they are allowed to do by their environment.” (Ray Peat, PhD, 2014)
For example, the p53 gene, known as the “guardian of the genome,” regulates cell division, DNA repair, and apoptosis. It prevents damaged cells from proliferating, acting as a major barrier to cancer. While mutations in p53 are common in cancers, they don’t always lead to malignancy.
A mutated p53 gene is not found in all cancers. In fact it is estimated that 87% to 99% of cancers with wild-type (non-mutated) p53 still have some level of impaired p53 function. This means that p53’s ability to prevent tumors can be disrupted in ways other than genetic mutations, such as changes in how the protein functions or how it interacts with other proteins in the cell. (For ex: other proteins in the cell can bind to p53 and block its activity).
In 2006, biologist Harry Rubin demonstrated that cells can accumulate hundreds of mutations and still function normally when they remain within the body. However, once removed from their natural environment and placed in a lab culture, abnormal cells begin to proliferate. Rubin believed the surrounding healthy cells within tissues regulate the behavior of mutated cells. These neighboring cells send signals encouraging the normal appearance, function, and growth patterns, preventing the mutated cells from acting like cancerous ones.
He wrote “intimate contact between the interacting cells is required to induce these changes.” Without this contact, the support needed for proper differentiation is absent. His research showed that mutations alone do not necessarily lead to cancer. The surrounding microenvironment is more significant.
So, what about BRCA? BRCA1 and BRCA2 mutations are strongly associated with an increased risk of breast and ovarian cancers, but they do not cause cancer outright. Here’s why:
- Not all BRCA mutation carriers develop cancer. Studies show that 20% to 55% of BRCA mutation carriers never develop cancer, even over a lifetime. A BRCA mutation alone is insufficient to drive malignancy. Other factors, such as the tissue microenvironment, inflammation, and especially hormonal imbalances have to be at play for cancer to develop.
- Cancer cannot develop in BRCA mutation carriers without the loss of the second BRCA allele. BRCA mutation carriers inherit one defective copy of the gene, but the second copy remains functional. Cancer typically requires the loss of the second BRCA allele, which may occur through errors in DNA replication or epigenetic changes. These errors often require environmental or metabolic factors like nutrient deficiencies, chronic inflammation, oxidative stress, or exposure to carcinogens such as xenoestrogens, radiation, or pollutants. Until this happens, the cell retains some DNA repair ability, preventing cancer from developing.
- Mutations are common in normal tissue. A 2024 study in Nature Genetics found that 3.25% of normal breast epithelial cells carried ‘cancer-associated mutations,’ including BRCA-related changes, in healthy tissue that never became cancerous.
- The best research we have on BRCA says that carriers are more sensitive to hormone imbalances, especially estrogen. We know that 80 percent of breast cancers are hormonally driven anyway.
Even though mutations are not the main drivers of cancer, DNA may still play a role through epigenetic changes like over-methylation.
Over-methylation involves adding methyl groups to DNA, often silencing tumor suppressor genes. This prevents these genes from repairing DNA, controlling cell growth, or initiating apoptosis. Unlike mutations, overmethylation is reversible. It is not a permanent alteration of the genetic code, so it can silence or activate genes without mutating them.
Over-methylation is triggered by factors such as chronic inflammation, oxidative stress, and exposure to environmental toxins like heavy metals and pesticides. These stressors activate enzymes like DNA methyltransferases (DNMTs), leading to the excessive addition of methyl groups that alter gene expression.
Alternate Theories:
Another theory, the Tissue Organization Field Theory (TOFT) challenges the traditional focus on mutations by proposing that cancer arises from disruptions in tissue. Unlike the somatic mutation theory, TOFT suggests that cancer emerges when the balance within the tissue microenvironment is lost.
Tissues operate as an integrated system, where cells are influenced by their neighbors, the extracellular matrix, and biochemical cues similar to what Rubin discussed in his research. When this system is disturbed, whether by chronic inflammation, physical injury, or environmental factors, it can trigger abnormal cell behavior without the need for specific genetic mutations. TOFT reframes cancer as a problem of systemic disorganization rather than an issue occurring in one dysfunctional cell. This offers new pathways for prevention and treatment that focus on restoring tissue harmony rather than targeting individual mutations.
The idea that cancer is a random, genetic mishap is not true. We know that mutations don’t just happen randomly. In fact, they are often triggered by environmental factors that damage DNA or disrupt cellular repair processes. Specific chemicals known to drive mutations include formaldehyde (found in building materials and household products), benzene (industrial emissions and personal care products), and arsenic (contaminated drinking water and certain pesticides).. These are just a few agents that introduce errors into the DNA or overwhelm the body’s ability to repair damage, increasing the likelihood of mutations. So, addressing our exposure to these harmful chemicals is a far more proactive approach than attempting to mitigate mutations after they occur.
It’s not just damaged DNA that drives cancer, but the disruption of the body’s regulatory systems—its tissue microenvironment, energy balance, and repair mechanisms—to keep cells in check. We have to look beyond the gene-centric view, because our success has been extremely limited so far.