Category: Prevention

Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database

The current study found low CRC mortality in path_MMR carriers who receive colonoscopy surveillance while some extracolonic cancers were associated with high mortality. Further improvement of survival in LS may require a focus on the prevention and treatment of non-colorectal cancers, likely including approaches based upon the immune response to MSI pre-cancerous lesions and cancers.

This study also provides more precise cumulative cancer incidences for path_MMR carriers than have been available previously, stratified by age, gene, organ, and gender.

https://www.sciencedirect.com/science/article/pii/S258953702300086X

What is Lynch Syndrome?

Be aware of gene changes and cancer in your family and take part in screening to reduce your risk of cancer.

https://www.cancer.ie/node/982

“I was told I was too young for it to be that”

https://www.bowelcanceruk.org.uk/how-we-can-help/real-life-stories/younger-people-with-bowel-cancer/tom-bartlett,-oxford/

Lynch Syndrome

Individuals with Lynch syndrome can reduce their risk for Colorectal cancer by:

1. Taking daily aspirin (exact dose & duration TBD).

2. Getting colonoscopy every 1-2 y starting at age 20-25 for MLH1/MSH2 & every 1-3y starting at age 30-35 for MSH6/PMS2.

Demystifying genomics in cancer care

Cancer is a disease of the genome, caused by unchecked cell growth due to mutations or changes in our DNA. Cancer genomics involves studying the genetic changes in cancer cells, allowing us greater insight into prevention, early detection, treatment, prognosis and recurrence.

In the case of cancer, a change is introduced which causes the cells to multiply uncontrollably – they become cancer cells and allow a cancer to develop. Most of the time these cancer-causing genetic changes are acquired i.e. they occur from damage to genes in a particular cell during a person’s life (also known as sporadic cancer). 

Why does cancer run in families?

Around 5-10% of cancers are caused by inherited or germline changes. This is where a genetic alteration occurs in a sperm or egg cell. It passes from the parent to the child at the time of conception and the alteration in the initial egg or sperm cell is copied into every cell within the body.

As the genetic alteration affects reproductive cells it can pass from parent to child and onwards to subsequent generations. Conditions such as Lynch Syndrome, is an example of an inherited cancer syndrome. This dominantly inherited conditions can greatly increase an individuals risk of developing cancer and mean that there is a 50% (or 1 in 2) chance that a parent can pass the genetic alteration onto their child.

Identifying a person with an inherited form of cancer is important. It means they can be looked after more closely in the future but it also has important implications for the family.

Genomics allows us to develop more precise treatments for cancer. Targeting treatments that focus on a cancer’s genetic makeup rather than where it has grown in the body.

https://www.macmillan.org.uk/healthcare-professionals/news-and-resources/blogs/demystifying-genomics-in-cancer-care

Constitutional (germline) vs Somatic (tumour) variants

Constitutional (also known as germline) variants are present in all the body’s cells, including the germ cells, and can therefore be passed on to offspring; somatic variants arise during an individual’s lifetime in tissues other than the germ cells and so are not passed on.

The identification of a germline variant in a mismatch repair (MMR) gene in a patient with colorectal cancer has implications for the clinical management of the current cancer and the patient’s future cancer risk. It should also trigger cascade screening in the wider family.

(Cascade testing is the process of informing family members of a genetic condition discovered within the family, followed by family members getting tested for the condition.)

MSH2 is the very young onset ovarian cancer predisposition gene, not BRCA1

Our study has shown that while the genetic predisposition for many early onset ovarian cancers is still unknown, MSH2 is the most important EOC predisposition gene at age <35 years.

The cumulative likelihood of an EOC in MSH2 heterozygotes would appear to be >2% by 35, with this likelihood still below 0.5% for BRCA1 and rare for BRCA2; indeed, two-thirds of cases identified in BRCA2carriers may not have been driven by HRD.

This increased incidence despite the good long-term survival in MSH2 should prompt awareness of the increased risk and consideration for early risk-reduction strategies.

(Flaum N, Crosbie EJ, Woodward ER, et al MSH2 is the very young onset ovarian cancer predisposition gene, not BRCA1 Journal of Medical Genetics  Published Online First: 09 March 2023. doi: 10.1136/jmg-2022-109055)

https://jmg.bmj.com/content/early/2023/03/08/jmg-2022-109055.share

Cancer Prevention Recommendations

“Our Cancer Prevention Recommendations are the conclusions of an independent panel of experts – they represent a package of healthy lifestyle choices which, together, can make an enormous impact on people’s likelihood of developing cancer and other non-communicable diseases over their lifetimes.”

Cancer Prevention Recommendations

Lynch syndrome prediction model

The PREMM5 model is a clinical prediction algorithm that estimates the cumulative probability of an individual carrying a germline mutation in the MLH1, MSH2, MSH6, PMS2, or EPCAM genes. Mutations in these genes cause Lynch syndrome, an inherited cancer predisposition syndrome.

N.B.:This website is provided for informational purposes only. The content is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your doctor or other qualified health provider with any questions you may have regarding your personal health or medical condition.

https://premm.dfci.harvard.edu