Author: Lynch Syndrome Ireland
“Variant of uncertain significance.” Few phrases on a genetic test report cause more confusion.
What is a variant of uncertain significance?
We all carry thousands of small differences in our DNA. Most are harmless and simply part of what makes each of us unique. A small number can change how a gene works and cause a health condition or increase the risk of one.
When a laboratory finds a genetic change, it classifies it using international guidelines. Variants are sorted into five groups: pathogenic, likely pathogenic, uncertain significance, likely benign and benign. A variant of uncertain significance, often shortened to VUS, sits right in the middle. It means there isn’t yet enough evidence to say whether the change is linked to disease.
VUS results are common, especially with larger panels that look at many genes at once. Receiving one is not unusual, and it is not a sign that something has gone wrong with your test.
• A VUS is not a diagnosis, and medical decisions shouldn’t rest on it alone
• Personal and family history still guide care
• Many VUS results are reclassified over time, most often to benign
Colonoscopy After 75?
Major health organisations, such as the U.S. Preventive Services Task Force and the American Cancer Society, do not use a strict “hard stop” at age 75.
Continued screening or surveillance may make sense if:
- You are in excellent overall health and have an expected lifespan of 10 or more years.
- You have never been screened before in your life.
- You have a high-risk history, such as a strong family history of colon cancer, a personal history of high-risk polyps, or inflammatory bowel disease (like Crohn’s disease or ulcerative colitis).
- You are experiencing symptoms like rectal bleeding, unexplained weight loss, or major changes in bowel habits—in which case a diagnostic (rather than routine screening) colonoscopy may still be recommended.
Artificial Intelligence in Colonoscopy Surveillance for Lynch Syndrome: Emerging Evidence, Lessons Learned From Average-Risk Populations, and Future Directions
Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome and is characterized by an accelerated adenoma-carcinoma sequence, a relatively higher prevalence of flat and subtle CRC precursor lesions, and exceptionally high adenoma miss rates despite intensive colonoscopy surveillance.
Existing LS-specific data suggest that AI can be safely integrated into high-quality surveillance. Meanwhile, use of AI has not yet been demonstrated to aid in improving overall adenoma or advanced neoplasia detection rates when used by expert colonoscopists, and when adequate baseline procedural quality is guaranteed.
Towards the future, efforts are required to develop more LS-specific training datasets and algorithms tuned to adenomas that are flat and have an MSI-driven morphology. Moreover, biologically aligned endpoints and multicenter prospective trials capable of measuring meaningful improvements in cancer prevention in LS carriers are needed. Only then can AI contribute to reducing the persistent burden of interval cancers in this high-risk population.
Bowel Cancer Ireland calls for bowel cancer screening age to be lowered
Delicious and Nutritious Recipes for People Living With Gastric Cancer
Prostate specific antigen (PSA) testing is a quick and simple blood test.
Did you know that if you have inherited Lynch Syndrome(a predisposition to cancer) you have an increased risk of Prostate cancer.
PROSTATE PROBLEMS AND YOUR PSA LEVELS
The prostate is a small gland that sits just below the bladder in men. Symptoms like the urge to urinate often or suddenly, including at night, blood appearing in your urine or semen, pain in your back or hips, or unexplained weight loss can be some of the signs that there’s a problem with the prostate, but it may not always mean cancer. A PSA test is a simple blood test that will help your doctor decide if further investigations are needed.
A shift towards prevention…
A broader ambition at Moderna: to push the boundaries of what is thought to be possible in medicine. Understandably, much of modern oncology has focused on treating cancer once it occurs. At Moderna, our oncology research to date has similarly focused on helping the immune system recognize and attack tumors that already exist. Now, we’re venturing into the preventative arena — can mRNA technology be applied to not only treat cancer after its diagnosis, but also to prevent cells from being a cancer growth, particularly for high-risk individuals?
mRNA technology works by instructing cells to produce specific proteins that can train the immune system to recognize and respond to disease. In the case of Lynch syndrome and mRNA-4194, we are investigating whether similar principles could train the immune system, specifically T cells, to detect and eliminate cells that carry these abnormal mutations before they grow into tumours.
We are just at the beginning of this journey, and there will be important insights along the way, deepening our understanding of Lynch syndrome and the potential of mRNA technology to address this high unmet need.
The INTERCEPT-Lynch Phase 1/2 trial is actively dosing participants with the investigational mRNA vaccine mRNA-4194 to prevent cancer in people with Lynch syndrome
https://www.modernatx.com/media-center/all-media/blogs/potential-mRNA-cancer-prevention
https://www.oncology.ox.ac.uk/research/clinical-trials/octo/trials/intercept_lynch
The hidden costs of cancer that nobody really talks about
When we talk about cancer, we talk about diagnosis, treatment, survival rates and recovery, but there is another side to cancer that often goes unseen – the financial cost of living through it.
♨️It is the extra heating because your body struggles to keep warm.
🚗The petrol, parking and public transport costs of travelling to endless hospital appointments.
🥪The food and drinks you need when you’re away from home for hours.
💊The prescriptions, supplements and other essentials that may not be covered.
🏠The household bills that keep coming, even when you’re too unwell to work.
💶The loss of income, reduced working hours, or a family member having to take time off to care for you.
Then there are the costs that come after treatment, the ongoing appointments, the long term side effects, the medications and the everyday adjustments needed to live with the consequences of cancer. Cancer doesn’t just affect your health, it can affect your savings, your independence, your family and your sense of security.
As someone living after a cancer diagnosis, I know that the end of treatment doesn’t necessarily mean the end of the costs.
Nobody should have to worry about whether they can afford to stay warm, travel to treatment or pay their bills while dealing with cancer.
We need to talk more openly about financial toxicity and recognise that the true cost of cancer goes far beyond the hospital walls.
FDA Approves Immunotherapy-Only Approach for Some Rectal Cancers: What Patients Need To Know
The method treats select cases of rectal cancer using only immunotherapy, which harnesses the body’s own immune system to fight cancer.
This allows some patients to skip standard of care treatment for rectal cancer which includes surgery, radiation, and chemotherapy, and can have life-altering consequences including infertility, incontinence, and more.
The FDA approved the use of an immunotherapy called Jemperli (dostarlimab), made by GSK, in people with stage 2 and 3 rectal cancer whose tumours have specific genetic characteristics known as mismatch repair-deficient (MMRd) or microsatellite instability-high (MSI-H).
Lynch syndrome is the best-known inherited condition that causes MSI-H or MMRd tumors. It’s linked to a higher risk of some types of cancer. They include colon cancer, rectal cancer, uterine (endometrial) cancer, and some cancers of the urinary tract.
https://www.annalsofoncology.org/article/S0923-7534(26)08070-1/fulltext
Highlights
AZUR-1 is the first registrational study evaluating dostarlimab monotherapy in a global dMMR/MSI-H LARC population
Over 90% of patients who were treated with dostarlimab have no evidence of disease progression to date
98% of evaluable patients who achieved cCR with dostarlimab alone maintained cCR for ≥12 months with no recurrences
Composite cCR at 12 months by investigator + pCR was 76%
Results support dostarlimab monotherapy as the new standard of care for dMMR/MSI-H stage II/III LARC
