Inheriting the first hit
In about 5–10% of cancers, a person is born already carrying the first hit. They inherit one broken copy of a key cancer gene as a germline mutation, present in every cell of the body. This is a hereditary cancer syndrome. Such people are not born with cancer — they are born one step closer to it, because every cell already has a brake half-disabled.
This is the two-hit hypothesis from guide 3, seen from the family's side. Because the first hit is already present in every cell, a single second hit anywhere can complete the loss — which is why these syndromes bring earlier average onset, a tendency toward multiple or bilateral tumors, and a pattern that shows up across generations of a family.
BRCA and Lynch: broken repair crews
BRCA1 and BRCA2 are tumor-suppressor genes whose normal job is DNA repair — specifically, fixing dangerous double-strand breaks accurately. When a BRCA copy is inherited broken and the second copy is later lost in a breast or ovarian cell, that cell loses a careful repair crew. Damage then piles up faster, raising the chance that other cancer genes get hit too. This is why inherited BRCA mutations sharply increase the risk of breast and ovarian cancer, and some others.
Lynch syndrome tells a similar story for the colon and several other organs. The inherited mutation disables a different repair system — mismatch repair, the proofreader that fixes typos made during DNA copying. Without it, mutations accumulate throughout the genome, dramatically speeding the path to cancer. Both stories share a theme: when the repair machinery is inherited weak, the whole genome becomes less stable — the topic of guide 5.
Risk is a probability, not a verdict
This is the most important — and most reassuring — idea in this guide. Inheriting a cancer-predisposing mutation raises risk; it does not guarantee cancer. The fraction of carriers who actually develop the disease is called penetrance, and for most cancer syndromes it is well below 100%. A second hit still has to happen, in the right cell, in the right tissue. Many carriers live long lives without ever developing the cancer their gene predisposes them to.
Because the stakes and the emotions are high, decisions about predictive testing for these genes are not made alone. Genetic counseling helps a person understand what a result would and would not mean, weigh screening or prevention options, and consider the impact on relatives who share the same gene pool. Knowing one carries a risk variant can be empowering — earlier screening catches more cancers early — but it is a personal choice, not an obligation.