Getting closer to understanding why eating fruit and vegetables lowers colon cancer risk
Medical science has understood for around two decades that eating fruit and vegetables has a protective effect when it comes to colorectal cancer, but has not clearly understood the mechanism. Recent research conducted by a team at South Dakota State University and published in March last year in the journal Cancers[1] may shed some light on this mechanism.
Previous research by the same group had focused on the beneficial effect of aspirin in preventing colorectal cancer and had identified a specific acid – 2,4,6-THBA – as being able to slow the growth of cancer cells. A subsequent search for natural sources of the acid discovered that the acid was produced when flavonoids – present in fruit and vegetables - are digested in the body.
"We hypothesized," said senior study author Jayarama Gunaje, Ph.D., "that flavonoids decrease colorectal cancer due to the action of the degraded, or broken down, products rather than the parent compounds."
Is personalised screening the future of colorectal cancer diagnosis?
Authors of a study by researchers based at the University of Western Australia (also involving researchers based in the Netherlands) published in the journal Cancer Epidemiology, Biomarkers and Prevention[2] last November puts the case for a more personalised approach to colorectal cancer screening, focusing on those more at risk of developing the condition first.
The current National Bowel Cancer Screening Program (NBCSP)[3] is a blanket invitation to all people aged 50-74 to take part in the national screening program every two years. It has a 40% participation rate and is estimated to have been responsible for saving the lives of around 10,000 people.
The researchers looked into the effectiveness of various screening approaches using a simulation involving 100 million 40 year old subjects and concluded that the optimal approach would be to use the current NBCSP testing regime but offering an annual test instead of one every two years. In addition the regime would identify high risk subjects by family history and polygenic risk score and offer them a colonoscopy every five years from the age of 50. This screening approach would be significantly more expensive than the current NBCSP system and the researchers admitted that on cost alone it would not stack up, but anticipated that it would become economically viable (analysed on a cost basis only) as costs for determining risk come down.
Does the immune system have a hard time detecting advanced bowel cancer cells?
Research published last November in the Journal for ImmunoTherapy of Cancer[4] suggests this might be the case. The immune system looks out for DNA faults on the surface of tumour cells and targets these cells and not healthy cells. These molecular 'flags' – or 'neoantigens' – determine whether a patient is likely to respond to immunotherapy, or whether immunotherapy treatment can be personalised to them.
This recent research by a team based at The Institute of Cancer Research in London (and working with another team at The Ludwig Institute for Cancer Research in Lausanne, Switzerland) showed that bowel cancer cells have far fewer neoantigens present on their surface than computer models predict. The researchers developed a new way of growing 'mini tumours' in large numbers from a patient tumour sample which then allowed mass spectrometry analysis of over 100 million cancer cells. This direct measurement of neoantigens gives more useful feedback than computer modelling and may in the future allow personalised 'vaccines' to be developed for each patient.
[1] The Flavonoid Metabolite 2,4,6-Trihydroxybenzoic Acid Is a CDK Inhibitor and an Anti-Proliferative Agent: A Potential Role in Cancer Prevention Cancers 2019 https://www.mdpi.com/2072-6694/11/3/427
[2] Cost-effectiveness of personalised screening for colorectal cancer based on polygenic risk and family history Cancer Epidemiology, Biomarkers and Prevention Nov 2019 https://cebp.aacrjournals.org/content/early/2019/11/19/1055-9965.EPI-18-1123
[3] See more information on developments with this program in our previous article
[4] Immunopeptidomics of colorectal cancer organoids reveals a sparse HLA class I neoantigen landscape and no increase in neoantigens with interferon or MEK-inhibitor treatment Journal for ImmunoTherapy of Cancer Nov 2019 https://jitc.biomedcentral.com/articles/10.1186/s40425-019-0769-8