Gene tests for constitutional (“germline”) cancer risk are evolving. We are getting better at finding needles in the haystack, but the haystack is bigger and there are more kinds of needles than we anticipated.
Genes, age and internal and external environment all influence our probability of getting cancer. The rate of lung cancer differs 20-fold by region, globally \cite{Bray_2018}, reflecting different rates of tobacco exposure. In contrast, female breast cancer is the most frequently diagnosed cancer in most countries, reflecting less modifiable internal hormonal influences. 5-10% of these cases arise from heritable causes such as susceptibility to breast cancer and ovarian cancer conferred by cancer susceptibility genes such as BRCA1 and BRCA2. A typical woman’s lifetime risk of breast cancer is about 12%, rising to 70% for a woman carrying one of these mutations \cite{Cline_2019}.