Genome-editing is helping us understand hereditary cancers better Premium

Discover how genetic mutations, like BRCA1 and BRCA2, impact cancer risk and personalized treatment strategies.

The International Agency for Research on Cancer’s estimates of the burden of 36 cancers in 185 countries suggest one in five individuals have a lifetime risk of developing cancer. The Agency also estimated that one in nine males and one in 12 females will die of cancer. In all, the agency counted 20 million new cancer cases and 9.74 million cancer-related deaths in 2022 and which it said could rise to a whopping 32 million new cases and 16 million deaths by 2045. By then Asia alone may account for almost half of all cases worldwide.

All cancers occur due to genetic mutations in the body’s genome and a subset of these cancers are the result of inherited mutations. Researchers have estimated that around 10% of all individuals with any cancer could have inherited a genetic mutation implicated in the cancer; they have also found the prevalence of inherited mutations to be higher among individuals with ovarian cancer (20%). It is 10% among those with breast, colorectal, lung or prostate cancers, and a lower 6% among those with cervical cancer.

Scientists have exhaustively documented hereditary cancers. We know there are more than 50 genetic syndromes (collections of symptoms) that predispose individuals to cancer and are caused by genetic variants that humans are capable of inheriting.

In fact, the discovery of the BRCA1 and the BRCA2 DNA-repair genes in 1994 and 1995, by Mary-Claire King et al. and Mark Skolnick et al. respectively, bolstered our understanding of hereditary cancer syndromes.

Hereditary breast-ovarian cancer syndrome is a relatively common cancer predisposition syndrome caused by mutations in the BRCA1 and the BRCA2 genes (or BRCA). In women, genetic mutations in BRCA primarily increase the risk of cancers of the breasts, ovaries and the fallopian tube. In men, they make prostate cancer and male breast cancer more likely. Many studies have also shown variations in the make-up of BRCA genes could increase the risk of pancreatic, colorectal, uterine, and some other cancers.

By some estimates, BRCA1 and BRCA2 mutations are present in around one in every 400 individuals, and therefore have an elevated risk of developing cancer. Researchers have also documented a higher than average prevalence in certain populations by virtue of these groups carrying specific variants of these genes. For example, among the Ashkenazi Jews that emerged in Central Europe and their descendants, around one in 40 individuals carry mutations in the BRCA genesis — about 10-times more common than in the general population.

This higher prevalence has been attributed to some genetic bottlenecks and founder effects within the community. A genetic bottleneck is when the genetic diversity in a population drops (due to various factors), leaving their gene pool ill-equipped to fend off diseases and other threats that require adaptation. When a small group of individuals with a genetic bottleneck found a new population, the bottleneck’s effects become pronounced in this group — a phenomenon called the founder effect.