23 October 2020 by Professor Annie Joubert
Globally, 14 million people are diagnosed with cancer each year, and about nine million lose their lives to the disease annually. But next-generation DNA technologies and sequencing are heralding a change to the outlook of the disease, and the rapid development and roll-out of DNA tests could save lives.
According to the World Health Organisation, between 30 and 50% of all cases are preventable – and campaigns such as Breast Cancer Awareness Month contribute to mindfulness of the disease, early detection and prevention strategies.
Cancer is ultimately a disease of the DNA. Humans have between 20 000 and 25 000 genes, but not all genes code for proteins – mutations in your genome influence your risk of being diagnosed with cancer, and could determine what happens during the course of the disease.
Breast cancer is one of the most common forms of the disease among women. In fact, the lifetime risk among South African women of getting breast cancer is one in 27, and about 7% of all breast cancer cases diagnosed occur in women under the age of 40.
According to the American Cancer Society, about one in eight invasive breast cancers develop in women younger than 45. In contrast, two in three invasive breast cancers occur in women aged 55 or older. This represents about 25% of all cancers in women. Breast cancer occurrence also differs between patients diagnosed before and after menopause.
But modern DNA technologies and next-generation sequencing are rapidly changing the face of this illness, diagnostics and treatment.
The role of mutations in the BRCA1 and BRCA2 genes in breast cancer susceptibility has been widely understood for some time. These genes produce proteins that are involved in processes that repair errors that occur in DNA. If they do not function correctly, these errors could lead to the development of cancer. However, over the past few years, it has become clear that many other genes also play a role in determining the risk of breast cancer, albeit with less significant effects than BRCA genes. About 15 primary genes have been identified that have mutations more often than expected in women who are diagnosed with breast cancer – but hundreds of other genes also potentially play a role. In some instances, mutations do not act alone, but lead to cancer only when they occur in concert with mutations in other genes.
In the early days of DNA technology, it was possible to determine the DNA sequence of a single gene at a time in an attempt to find mutations related to cancer. Today, it has become realistic to obtain the complete genome sequence of a cancer patient together with the profile of genes being activated and deactivated. This genomic picture can then be used to assess someone’s cancer risk, better understand a cancer diagnosis, and design tailor-made treatment strategies. This is a form of precision medicine, more specifically referred to as personal oncogenomics.
Two broad sets of tests analyse mutations in DNA: there are those that investigate the mutations that someone was born with and are aimed at assessing the risk of being diagnosed with cancer (germline cancer susceptibility analysis), and those that analyse the mutations in tumours of someone who has been diagnosed with cancer (somatic mutation analysis). Cancer susceptibility analysis could help to determine whether a person should be examined for cancer more regularly with additional screening tests. Somatic mutation tests could help oncologists understand what happened when cancer developed and guide them in further testing and treatment.
Access to advanced testing is typically through a cancer centre or an oncologist, who will arrange for the analysis of samples by a pathology company or specialised DNA analysis company, with subsequent consultations with an oncologist and a genetic counsellor. While a few years ago, only BRCA1 and BRCA2 testing was commonly available, cancer centres around the world, particularly in the USA, Europe and Asia, are now making regular use of large cancer susceptibility and somatic mutation testing panels. International consortia are building vast databases of mutations in cancer patients and correlating the mutations to the choice of successful treatment methods.
About 5 to 10% of cancers can be attributed to genetic inheritance. DNA mutations could be present for several other reasons that may occur after birth. This could be triggered by risk factors such as the use of tobacco products, alcohol consumption, diet, environmental pollutants, ultraviolet radiation, reproductive and hormonal factors, occupational exposures and infection-attributable cancers.
As with most cutting-edge technologies, many testing approaches come at a high price, aren’t yet widely available, have not yet been approved for clinical use in all countries, aren’t covered by medical aid, and are sometimes available only to patients who are included in large research trials. What is clear is that the rapid development and roll-out of these tests could save lives.
Professor Annie Joubert is Head of the Department of Physiology at the University of Pretoria. Breast Cancer Awareness Month is observed annually in October.