It should come as no surprise, therefore, that somatic mutations are
questioned as representing “the” cause for the majority of cancers
[10,11] and it should be noted that some cancers are not associated
with any mutations whatsoever.
Importantly, a detailed analysis of 31,717 cancer cases and 26,136
cancer-free controls from 13 genome-wide association studies [48]
revealed that “the vast majority, if not all, of aberrations that were
observed in the cancer-affected cohort were also seen in cancer-free
subjects, although at lower frequency” [47]. Thus, the notion that
somatic mutations are necessarily harmful and can lead to cancer is
not borne out by this study and further affirms the hypothesis that
mutations observed in cancers are not the triggering event but more
likely a means for the clonal replication of already transformed
cancer cells.
However, despite 65 years of research on the mutation theory, there is
still no proof for even one set of mutations that is able to convert a
normal cell to a cancer cell.
Because the prevailing mutation theory has dominated the search for
the genetic causes of cancer since the discovery of gene mutation in
1927 [111], consistent mutations or consistent karyotypic
abnormalities with specific mutations were expected [15,21,22].
Instead, individual mutations [43,44] and individual karyotypes
[2,9,112,113] were found, of which over 68,000 are listed in the
NCI-Mitelman database of cancers [6].
When the first results of The Cancer Genome Project were reported,
many scientists were shocked to learn that most patients, including
those with the same type of cancer, did not share the same
cancer-related mutations.
The DNA Theory predicts that cancer will be more common in cells that
replicate more frequently and/or in organs that have more cells.
Lintern’s theory suggests more cancer in organs that have more surface
area that are accessible by fungi. I think the evidence favors Lintern
here, but probably not very strongly.
Importantly, a detailed analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies [48] revealed that “the vast majority, if not all, of aberrations that were observed in the cancer-affected cohort were also seen in cancer-free subjects, although at lower frequency” [47]. Thus, the notion that somatic mutations are necessarily harmful and can lead to cancer is not borne out by this study and further affirms the hypothesis that mutations observed in cancers are not the triggering event but more likely a means for the clonal replication of already transformed cancer cells.
Isn’t case-control GWAS the wrong tool for the job since it’s blind to rare mutations? I’d compare a person’s cancerous cells to their normal cells instead, though I’m not an expert so maybe there’s a problem with this.
This comment describes some relevant research.
From Somatic Mutation Theory—Why it’s Wrong for Most Cancers:
From Speciation Theory of Carcinogenesis Explains Karyotypic Individuality and Long Latencies of Cancers:
The tissue organization field theory of cancer: A testable replacement for the somatic mutation theory
From Cancer Treatment: A Systems Approach
The DNA Theory predicts that cancer will be more common in cells that replicate more frequently and/or in organs that have more cells. Lintern’s theory suggests more cancer in organs that have more surface area that are accessible by fungi. I think the evidence favors Lintern here, but probably not very strongly.
Itraconazole therapy in a pancreatic adenocarcinoma patient: A case report: an example of a patient with a terminal cancer diagnosis recovering in apparent response to getting an anti-fungal drug.
Case studies with salvestrol treatment: a class of natural anti-fungals helped cure some “terminal” cancer patients. 6 more case studies. New clinical study with phytonutrients (phytoalexins) a randomized controlled trial.
Fungal diseases mimicking primary lung cancer: radiologic—pathologic correlation: cancer and fungal infections look similar. Somehow, this is rarely taken as evidence that they’re the same thing.
How a plant’s anti-fungal defence may protect against cancer.
From Finding the “Missing 50%” of Invasive Candidiasis:
Isn’t case-control GWAS the wrong tool for the job since it’s blind to rare mutations? I’d compare a person’s cancerous cells to their normal cells instead, though I’m not an expert so maybe there’s a problem with this.