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}.