Women are being unnecessarily alarmed about their risk of breast cancer by consumer genetic test results that do not take family history into account, researchers have said.
Women who discover outside a clinical setting that they carry a disease-causing variant of the BRCA1 or BRCA2 genes may be told that their risk of breast cancer is 60-80%. But analysis of UK Biobank data suggests the risk could be less than 20% for those who do not have a close relative with the condition.
Dr Leigh Jackson, of the University of Exeter’s medical school, who is the lead author of the analysis published in the journal eClinical Medicine, said that in extreme cases this could result in women unnecessarily undergoing surgery.
“Being told you are at high genetic risk of disease can really influence levels of fear of a particular condition and the resulting action you may take,” he said. “Up to 80% risk of developing breast cancer is very different from 20%.”
NHS clinical geneticists already routinely factor family history into risk scores, making it unlikely that women are going ahead with surgery on a misinformed basis. However, doctors said that by the time some women arrived in their clinics, they were already strongly inclined to opt for a mastectomy after learning that they carry a BRCA mutation.
“From a psychological point of view, it is very difficult if you’re a woman and this comes out of the blue,” said Prof Marc Tischkowitz, the head of medical genetics at the University of Cambridge, who was not involved in the research. “No matter what a professional says, that initial shock stays with you and you’re kind of inclined not to be so reassured. It’s definitely an issue that we then have to deal with.”
The authors analysed more than 454,000 people recruited between the ages of 40 and 69 into the UK Biobank study, which collects DNA samples and asks participants to report illness in themselves as well as in parents and siblings.
They found that carrying a disease-causing BRCA variant was linked to a breast cancer risk of 18% (for BRCA2) and 23% (for BRCA1) by age 60. Having a close relative who has had the condition elevated the risk to 24% (for BRCA2) and 45% (for BRCA1). The researchers said these figures could underestimate the risk slightly, due to people who have died early from breast cancer not being included in the cohort.
Until recently, women who received BRCA results did so because they had attended clinic due to symptoms or a family history of disease. However, an increasing number are now learning of their genetic risk after paying for home DNA testing kits or taking part in genetic research, without ever having any personal link with breast cancer. The latest study suggests that the risk carried by BRCA variants depends on secondary genetic factors, meaning family history is crucial for understanding an individual’s risk.
Prof Caroline Wright, of the University of Exeter medical school, said: “Our findings will not just apply to breast and colorectal cancer. All risk estimates of genetic disease have so far largely been based on relatively high-risk groups who attend specialist clinics, so they will not necessarily translate to the general population. We need to ensure we are carrying out research to find the true risk level, and also to be responsible in how we communicate risk, to avoid unnecessary fear and distress which may lead to avoidable procedures.”
