Genetic Factors and Environmental Risks Contribute to Colon Cancer

Researchers at the University of Melbourne have identified new insights into the genetic and environmental factors contributing to colon cancer. Specifically, they have found that non-genetic factors such as environmental risk factors, prior oncologic treatments, and bacterial genotoxins colonizing the intestine, particularly colibactin-producing Escherichia coli, play a significant role in the development of multiple adenomas and colorectal cancer.

Key Takeaways:

• Adenomatous polyposis syndromes are hereditary conditions characterized by the development of multiple adenomas in the gastrointestinal tract, significantly increasing the risk of colorectal cancer.
• Germline pathogenic variants in genes involved in Wnt signaling and DNA repair cause these syndromes, while autosomal dominant adenomatous polyposis syndromes include familial adenomatous polyposis (FAP) and polymerase proofreading-associated polyposis (PPAP).
• Autosomal recessive syndromes include those caused by biallelic pathogenic variants in the DNA mismatch repair genes MLH1, MSH2, MSH6, PMS2, MSH3, and MBD4, and in the base excision repair genes MUTYH, NTHL1, and MBD4.
• Genetic testing for hereditary adenomatous polyposis syndromes is complex, involving considerations for post-zygotic mosaicism, non-coding pathogenic variants, and the interpretation of variants of unknown significance.
• Non-genetic factors such as environmental risk factors, prior oncologic treatments, and bacterial genotoxins colonizing the intestine significantly contribute to the development of multiple adenomas and colorectal cancer.

Statistics:

• 24.2% of cases of multiple adenomas remain genetically unexplained (Source: Familial Cancer, 2025;24(2)[1]).
• Germline pathogenic variants in APC, POLE, and POLD1 genes cause familial adenomatous polyposis (FAP) and polymerase proofreading-associated polyposis (PPAP) (Source: University of Melbourne, Dept. of Clinical Pathology, Colorectal Oncogen Grp, Parkville, Vic, Australia[2]).
• Bacterial genotoxins colonizing the intestine, particularly colibactin-producing Escherichia coli, have emerged as an alternative pathogenic mechanism (Source: Genetic and molecular mechanisms underlying hereditary adenomatous polyposis syndromes[3]).

Sources:

[1] Familial Cancer, 2025;24(2).

[2] University of Melbourne, Dept. of Clinical Pathology, Colorectal Oncogen Grp, Parkville, Vic, Australia.

[3] Genetics, Genomics and Clinical Features of Adenomatous Polyposis.