Study finds polyps can aid early detection of hereditary bowel cancer

Researchers have found that studying tissue samples from bowel polyps can identify people with hereditary bowel cancer syndromes.

The study, published in Translational Oncology, and led by Dr Romy Walker, Dr Peter Georgeson and Associate Professor Dan Buchanan from the Colorectal Oncogenomics Group at the Collaborative Centre for Genomic Cancer Medicine—a joint venture of the University of Melbourne and Peter MacCallum Cancer Centre—found that the pattern of somatic mutations that develop in adenomas, (pre-cancerous growths in the colon) can identify people with the inherited colorectal cancer syndromes MUTYH-associated polyposis and NTHL1-associated polyposis.

Dr Romy Walker and Dr Peter Georgeson

Somatic mutations are acquired, not inherited. People with these genetic syndromes have an extremely high risk of developing colorectal cancer if left untreated. Identifying them before cancer develops provides opportunities for prevention through increased screening and early detection. This can guide timely interventions and treatment to stop cancer from occurring.

"We've shown the diagnostic potential of measuring somatic mutational signatures in colorectal adenoma tissue,” Dr Walker said.

“We have previously shown that measuring the colorectal cancer tissue is diagnostically informative, but these findings show that measuring pre-cancerous tissue has the same diagnostic accuracy – which gives us the opportunity to identify patients with a hereditary colorectal cancer syndrome before they develop cancer."

"This is significant as people often develop polyps prior to cancer, and polyp samples can also be used if bowel cancer tissue is not available for testing. We want to identify people at risk earlier and prevent cancer from developing in the first place."

"Diagnostic labs could include testing of polyps for mutational signatures linked to specific cancer syndromes, to identify an increased risk of bowel cancer. This would then inform clinical guidance by providing personalised, risk-stratified recommendations for screening or surgical prevention such as colonoscopies or removal of parts of the colon."

Dr Georgeson said that the research has also enabled the classification of variants of unknown significance—genetic variants or mutations whose effects on disease risk are not yet clearly understood complicate clinical decision-making and result in a state of limbo for the patient and uncertainty around the best clinical management.

“Variants of uncertain significance are a major problem in clinical genetics. People carrying a variant of uncertain significance are at risk of undergoing unnecessary treatment and may suffer from adverse psychological effects.”

“Our findings have expanded the potential for mutational signature profiling to re-classify gene variants as pathogenic (disease causing) or benign (not related to disease) providing more certainty for the patient and treating clinician."

"We're excited that this research has added to the growing evidence that analysing mutational signatures—the patterns of mutations found in genes—can be a useful clinical tool for identifying hereditary cancer syndromes and improving variant classification approaches."

The integration of these findings into routine clinical practice could improve the identification of “high-risk” people before cancer develops, which could help alleviate burden on the healthcare system, improve personalised, risk-appropriate treatment, and provide more clarity for patients.