While I was thinking recently about how reverse osmosis filters can elevate the amount of hydrogen peroxide (H2O2) in our mouths and digestive tracts by removing fluoride F−ions from our drinking water, I thought of a teenage boy I know of who lives in a fluoride-avoiding household with a reverse osmosis filter and who was diagnosed in 2020 with Stage 4 colorectal cancer. He is still alive in 2023, but it's been a hard fight against the cancer.
It is highly unusual for someone his age to have aggressive colorectal cancer. I wondered whether there could be a connection between having more H2O2 in the gastrointestinal tract and his youthful development of colorectal cancer. Here is what I found:
Regarding direct genotoxic mechanisms, [cobalt(II)] induces the formation of reactive oxygen species when combined with hydrogen peroxide in cell-free systems. At high (i.e., millimolar) concentrations, [cobalt(II)] also decreases the fidelity of DNA synthesis.
Beyersmann D, Hartwig A. The genetic toxicology of cobalt. Toxicology Applied Pharmacology 1992;115(1):137-145, ISSN 0041-008X, https://doi.org/10.1016/0041-008X(92)90377-5. Online at https://www.sciencedirect.com/science/article/pii/0041008X92903775.
Cobalt has already been noted to impair DNA replication and damage DNA (see "Cobalt and nickel impair DNA metabolism by the oxidative stress independent pathway" online at https://pubs.rsc.org/en/content/articlelanding/2017/mt/c7mt00231a). Cobalt has been found to be associated with colon cancer (see "Association between heavy metals and colon cancer: an ecological study based on geographical information systems in North-Eastern Iran" online at https://pubmed.ncbi.nlm.nih.gov/33858386/). Taking vitamin B12--the only vitamin that contains cobalt--appears to increase the risk of developing colorectal cancer (see "Folic Acid and Vitamin B12 Supplementation and the Risk of Cancer: Long-term Follow-up of the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) Trial" online at https://doi.org/10.1158/1055-9965.EPI-17-1198; see also "Genetically predicted circulating B vitamins in relation to digestive system cancers" online at https://www.nature.com/articles/s41416-021-01383-0).
Failure to accurately replicate DNA (i.e., decreased DNA synthesis fidelity) has been found to increase susceptibility to early-onset colorectal cancer, per an interesting 2010 article:
Perhaps the strongest early evidence that increased spontaneous mutation (i.e., mutator phenotype) contributes to human cancer was the discovery that defective mismatch repair (MMR) causes hereditary colon cancer....In the early 1990s, colorectal cancer samples from Lynch syndrome pedigrees (also called hereditary nonpolyposis colon cancer or HNPCC) were noted to have microsatellite instability, normal cytogenetics, and were associated with a unique clinical presentation. Two groups simultaneously reported that these families carried mutations in MSH2, the gene encoding one of the primary proteins required for MMR. Shortly thereafter, MLH1, the gene encoding another essential MMR protein, was cloned and found to be mutated in additional Lynch syndrome families. The majority of Lynch syndrome patients inherit a mutation in either MSH2 or MLH1, with a smaller percentage inheriting mutations in PMS2 or MSH6. The wild-type allele is then lost in tumors through LOH or gene silencing. Patients with inherited MMR deficiency are primarily susceptible to early-onset colorectal cancer, but also have an increased risk for extra-intestinal neoplasms. Inherited MMR defects are only responsible for a small number (1–5%) of colorectal cancer cases; thus, most colorectal cancers with MSI (~15% of all colorectal cancer cases) result from acquired defects in MMR, almost exclusively due to MLH1 promoter hypermethylation. MMR defects and MSI are also detected in non-colonic sporadic tumors, most commonly in endometrial, lung and gastric cancer.
Preston BD, Albertson TM, Herr AJ. DNA replication fidelity and cancer. Semin Cancer Biol. 2010 Oct;20(5):281-93. doi: 10.1016/j.semcancer.2010.10.009. Epub 2010 Oct 15. PMID: 20951805; PMCID: PMC2993855. Online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993855/.
As far as I have heard, the parents of this family encourage the use of vitamins, especially B vitamins. It appears that their desire for clean water and adequate vitamins might have inadvertently contributed to DNA replication issues in their son that could be behind his unusual early-onset colorectal cancer.
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