Only 5 per cent of colorectal polyps lead to colorectal cancer but mismatch genes, an immune response and localised bacterial changes may be the reason for the increased inflammation and cancer.
A colon polyp is a small clump of cells that forms on the gut wall. Most are harmless but over time some can turn into cancer. Smokers, people over 50 and people with a family history of polyps are at a higher risk. The problem is that they don’t cause any symptoms, only when they become cancerous does a problem emerge.
A Mayo Clinic study has shown that one in six cases of colorectal cancer are caused by hereditary mutations (1).
Lynch syndrome and mismatch genes
One hereditary condition is Lynch syndrome - this raises colorectal cancer risk through colon polyps, but these do display warning signs with an immune system response well before cancer development, according to research from The University of Texas MD Anderson Cancer Center (2).
Their research challenges traditional models of cancer immune activation and suggests colorectal cancer grows in a background of ‘mismatch’ repair deficiency leading to the accumulation of high numbers of l;ocalised mutations. This in turn causes an attack by large numbers of lymphocytes, providing a unique immune profile with upregulation of immune blockages.
Researchers suggested immunotherapy drugs such as Pembrolizumab might be a useful treatment if someone with Colorectal cancer has mismatch genes and certainly at CANCERactive, we have seen such patients do well on Pembrolizumab. Nivolumab is a rival PD-1 immunotherapy drug. The original research was presented back in 2018 at the American Association for Cancer Research Annual Meeting.
Genetic testing for mismatch genes
There is now genetic testing (3) for inherited colorectal cancer and polyposis, Lynch syndrome (LS) is the most common hereditary colorectal cancer syndrome, caused by variants in the mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2
Gut bacteria increase polyp conversion into Colorectal cancer
Research from William DePaolo, associate Professor at the University of Washington School of Medicine, studied 40 people in a preliminary study. All had colonoscopies, and the ones with polyps had samples of the microbiome removed from the local area.
Only 5 per cent of people with polyps end up with Colorectal cancer but the polyps occur in the same places with some consistency
The research (4) showed that where there was inflammation around the polyps, there were higher levels of the bacterium Bacteroides fragilis, linked to higher levels of inflammatory cytokines.
However, the B. fragilis appeared to be slightly different to the seemingly harmless B. fragilis found normally in the gut implying that either it was a different strain or other bacteria in and around the polyp were modifying the bacterium.
DePaolo plans a bigger study adding that it was important to look at the contribution of the microbiome before cancer occurred rather than once it had done, especially given the rapid growth in numbers of this cancer and its ever younger profile.
Go to: Are antibiotics the reason for increases in younger Colorectal cancers?
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References
1. Comparison of Universal Genetic Testing vs Guideline-Directed Targeted Testing for Patients With Hereditary Cancer Syndrome; N. Jewel Samadder et al; JAMA Oncol. 2021;7(2):230-237.
2. Lynch syndrome premalignancy upregulates immune checkpoints independently from neoantigen and mutational rates; Kyle Chang, MD Anderson, April 16, 2018
3. Genetic testing for inherited colorectal cancer and polyposis, 2021 revision; Rong Mao et al; Genetics in Medicine volume 23, pages 1807–1817 (2021)
4. Genomic and functional characterization of a mucosal symbiont involved in early-stage colorectal cancer; Melissa C. Kordahi, R. William DePaolo et al. Cell Host & Microbe, 2021;