10 Top Tips: Genomics and Cancer

GPs have an important role to play in supporting patients through the diagnostic and treatment processes for cancer.

As the availability of genomic testing increases within the NHS and private sectors, part of this role will incorporate a clinical understanding of genomics. Primary Care are likely see an increasing number of patients presenting to them with questions about their personal risk or test results, those with a family history of cancer who may benefit from genetic testing, and those undergoing treatment who are seeking advice about targeted therapies.

GPs need to have the resources and skills to deliver genomic conversations, to identify those at risk of a genetic condition, and to clinically manage genetic condition.

The NHS England's Genomic notes for clinicians website is a useful resource that contains clinical case studies of genomics in primary care.

A copy of the genome (all of someone’s DNA) is found in nearly every cell in the body. Genomic changes in a person’s DNA, also called variants, are either acquired over time or inherited/hereditary (germline).

Acquired variants

Acquired variants that build up over time are the most common cause of cancer. These are usually caused by “wear and tear” damage on genes over time like:

• aging
• exposure to hormones
• smoking
• environmental toxins
• and certain viruses.

These variants are also called ‘somatic variants’ and are only present in the cancer cells. They cannot be passed onto any children.

Germline variants

Germline variants are less common and play a role in about 5% to 10% of cancers. These changes are present in every nucleated cell in the body and have been since birth.

These changes can be passed on to the next generation, so may have an impact on family members.

They are often associated with the following features:

• multiple primary tumours in the same organ or different organs
• cancer at a young age (less than 50 years old)
• tumours occurring in the sex not usually affect, like breast cancer in men
• tumours associated with other genetic traits or another rare disease
• family history of a cancer type or cancer syndrome.

Most changes within the genome are harmless, and do not lead to disease. However, there are a small number of inherited variants in the genome that can increase an individual’s risk of cancer over their lifetime.

These result in a higher than usual chance of recurrence after primary cancer.

For example, people who have a CDK4 variant have a high lifetime risk of melanoma, which is up to 80% compared to a population risk of 2.5%.

Somatic variants only occur in the non-germline cells of the body. Therefore they cannot be passed from parent to child.

Changes in these cells can be caused by exposure to environmental factors over a person’s lifetime. For example, damaging UV rays from the sun cause changes in the base pairs of DNA within the cell. These changes can accumulate over time which can lead to uncontrolled cell growth and tumour formation.

These changes can be detected by sequencing the tumour’s genome, by comparing the sequence from the patient’s blood sample and the sequence from a sample of their tumour.

It is important for GPs to understand the concept of germline testing for hereditary predisposition to cancer and somatic testing and its role within targeted therapies by identifying a tumour’s ‘genetic signature’.

This is because language is important. When patients hear the term “genetics linked to their cancer diagnosis" this can generate considerable anxiety. It may lead to an inappropriate referral for testing of family members when the reference is to somatic testing.

Our Hallmarks of Heredity Risk: When to Test poster is a helpful resource for GPs to understand when a patient may need to be referred for further testing.

Written by Antigone Johnstone-Burt 

Next planned review March 2025

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