Examples of actionable genes we are screening for at The London Genetics Centre

CANCER GENE EXAMPLES

Breast and Ovarian Cancer

Some genetic anomalies such as BRCA genes occur quite frequently in the general population- 1 in 300 people.?In the Ashkenazi Jewish population, they occur as frequently as 1 in 40 people.?

Lynch syndrome

A genetically defined condition with a high risk of colon cancer, uterine cancer, and other cancers – it probably occurs in about 1 in 279 people. Colonoscopy screening may reduce the colon cancer mortality by up to 70-75 percent. In the case of Lynch syndrome, colonoscopy screening should be started as early as 25 years of age, in some cases.

Prostate Cancer

Prof Eeles has published data to show that men who carry alterations in the BRCA2 should be offered regular prostate screening. She is investigating whether screening other prostate cancer risk genes improves outcome.?

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CARDIAC GENES

Aortopathies

Certain genes may cause aortic disease, such as aortic aneurysms - or aortic dissections, where the main artery coming from the heart enlarges and can burst with usually fatal consequences. Knowledge of their presence may mean specific actions can be taken to dramatically reduce the mortality rate of such conditions.?

?Familial hypercholesterolaemia

A gene alteration which causes severely elevated cholesterol levels from birth and results in men having an 80 per cent chance of a heart attack by the age of 60. A woman’s risk profile is about 10 years behind a man’s.

It has a frequency in the population of approximately 1 in 250 and affects ~250,000 people in the UK. So far three main gene variants have been found that cause 80 percent of this condition - the 3rd?was found in 2003. The risks of these genes can be dramatically lessened by treatment.

Cardiomyopathy?

We identify a gene change in 15-25% of cases of Dilated cardiomyopathy (so-called familial dilated cardiomyopathy), where the heart muscle is like a floppy bag. It occurs in approximately 1 in 2,000-2,500 people. By detecting this condition early, medicines can be started that are highly effective and genetic counselling can help to identify additional asymptomatic family members.?

Hypertrophic cardiomyopathy

This is a genetic condition where there is harmful thickening of the heart muscle, which occurs in 1 in 500 people. Early diagnosis can lead to an improved outlook.?A gene change is identifiable in 30-60% of cases; for this reason, all individuals who undertake Whole Genome Screening at The London Genetics Centre do an echocardiogram.

Long QT Syndrome

This condition occurs in approximately 1 in 2,500 people. Alterations in specific genes can cause a prolongation of part of the electrocardiogram called the QT interval. This can then be associated with an increased risk of life-threatening cardiac rhythm abnormalities.?The knowledge of such a genetic alteration being present can mean that patients are not given drugs that may increase their QT interval length, thereby reducing risk.?

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NON-CANCER/NON-CARDIAC EXAMPLES

Factor V Leiden

Factor V Leiden occurs in about 8 percent of the population This gene alteration gives an increased rate of clots (deep vein thromboses) of about five times the normal population. It is present in up to 30 percent of patients with a deep vein thrombosis or potentially fatal pulmonary embolism. Another pro-clotting gene, the Prothrombin mutation, occurs in 2-3 percent of the UK population and increases the risk of clots three-fold.

Haemochromatosis

Haemochromatosis is a condition where patients retain excessive iron which is damaging and potentially fatal, due to toxicity to organs such as the liver, pancreas, and heart. Over 380,000 people in the UK have this genetic predisposition and yet only 10,000 are diagnosed.

1 in 200 have the genotype of both of their chromosomes having the so-called C282Y variant which causes 95 percent of haemochromatosis. If you are found to have the gene alteration, simply taking some blood from time?to?time, successfully depletes the?iron stores so preventing organ toxicity.