As I have discussed previously, genetic technology is developing at a breath-taking speed. This not only means that scientists gain better insights in the genetic contributors to disease development, but also that this comes at increasingly lower costs.
Genetic testing is not new. In fact, it has been available on the NHS for many years. However, to be eligible for testing, certain criteria have to be met; commonly, people need to have several affected relatives to qualify for genetic testing on the NHS.
Now, with falling sequencing costs, the question of whether it would be beneficial to offer genetic testing to everyone in the population before conditions manifest becomes ever more pertinent. Proponents of the proposal argue that current approaches based on family history may miss a proportion of individuals because both individuals and healthcare providers have to recognise that there may be an increased risk of disease – this can be challenging if the family is small, or people are not very actively seeking out this information. However, other experts are more cautious and argue that large-scale genetic testing has the potential to cause more harm than good. Regardless, there are many practical, social, legal and ethical questions that have to be sorted out before genetic testing can be applied at a population level.
Currently, in the clinical setting, genetic testing is only performed after thorough genetic counselling. Genetic counselling is defined as ‘a communication process, which aims to help individuals, couples and families understand and adapt to the medical, psychological, familial and reproductive implications of the genetic contribution to specific health conditions’. Genetic counsellors meet with people one-to-one and help them to make a decision whether or not they’d like to have testing. Although research to date has found that people commonly do not react badly to their genetic test results, genetic counselling is thought to play a large role in this because people would have discussed the possibility of an unfavourable result before they got testing. In addition, because people who get genetic tests to date come from high-risk families, they may to have thought a lot about their inherited risk. Therefore, they may be better prepared to cope with an unfavourable genetic test result.
However, if lots of people in a population got genetic testing, the one-on-one model of genetic counselling would be impossible to maintain because it is far too costly and time-intensive. Some experts are concerned that providing access to genetic testing without proper genetic counselling to people who may be largely unaware of their inherited risk would result in a high rate of adverse psychological effects such as worry and anxiety.
In the first study of its kind, our researchers wanted to find out what the effects of population-based genetic testing would be. They chose to look at the effects of returning genetic test results for risk of breast-and ovarian cancer (BRCA 1/2) in the Ashkenazi Jewish population. They picked this population because people of Ashkenazi Jewish descent have a higher chance to get breast-and ovarian cancer than people from other backgrounds and the mutations causing the increased risk are well-defined. People with one of these mutations have a very high chance to get cancer (50%-80% for breast; 20%-40% for ovarian).
Specifically, the researchers wanted to investigate i) whether population-based genetic testing would be able to identify a greater proportion of mutation carriers than the current family history approach, ii) whether people would find testing acceptable, and iii) what the psychological effects (e.g. on anxiety and depression) of genetic testing would be in people which may not necessarily have a strong family history of breast-or ovarian cancer.
Potential participants were recruited in the North London Jewish community. All individuals who registered their interest received genetic counselling before they enrolled into the study, and 1,034 (691 women, 343 men) decided to take part. Participants were randomly (by chance) split into two equally sized groups: In one group, all people would get genetic testing, and in the other, only people who would qualify for genetic testing under current NICE guidelines would get testing. However, this group could access testing after the end of the study if they wanted.
Our researchers asked questions about people’s anxiety levels, depression, and general quality of life before people got genetic counselling (baseline); immediately after study enrolment; and at seven days and three months after people got their genetic test results. The researchers also asked the same questions after one, two and three years after people got their genetic test results, but the results of this bit of the study have yet to be analysed.
In the group where all people were tested for their BRCA status, 13 carriers of a faulty gene were identified vs. 9 in the group which based the testing decision on family history; an increase in detection of 56%. In the family history group, 5 more carriers were detected after the study had finished. This means that current approaches are likely to miss a significant number of people of Ashkenazi Jewish descent who carry faulty BRCA mutations. As for adverse psychological effects, there were no differences between the 2 groups at either 7 days or 3 months after people received their genetic test results. In fact, overall anxiety and uncertainty decreased quite a bit, and positive experience scores increased.
This study is the first to provide evidence that large-scale genetic testing may be beneficial and feasible; at least in certain subgroups of the population. However, in this study, all participants received one-to-one genetic counselling before they enrolled; so it is not possible to say what the effects would have been using a less tailored approach. This might be something that could be investigated in future research. Nonetheless, these results demonstrate that large-scale genetic testing may have real clinical value, and they may spark serious debate about whether the current guidelines should be amended, at least for people of Ashkenazi Jewish descent. After all, identifying BRCA carriers early may save lives.
Manchanda R, Legood R, Burnell M, McGuire A, Raikou M, Loggenberg K et al.: Cost-effectiveness of population screening for BRCA mutations in Ashkenazi Jewish women compared with family history-based testing. J Natl Cancer Inst 2015, 107.
Manchanda R, Loggenberg K, Sanderson S, Burnell M, Wardle J, Gessler S et al.: Population testing for cancer predisposing BRCA1/BRCA2 mutations in the Ashkenazi-Jewish community: A randomized controlled trial. J Natl Cancer Inst 2015, 107