Familial Cancer: Why is the second mutation so common?
BRCA1 gene mutations can lead to increased risk for cancer.
Germline mutations in the BRCA1 gene can be passed on to people that will then become carriers of the faulty gene.
The lifetime risk to develop an associated cancer (breast cancer, ovarian cancer etc. ) for someone carrying this heterozygous defect is very high (around 60%). Since they already have one faulty gene, they are more susceptible for the 2nd gene to become faulty as well (the two hit hypothesis), and thus these inherited cancers have an earlier onset too.
How come there is such a stagerring risk (60%) for a person to develop cancer when one of their alleles is fine? Spontaneous mutation chances alone surely cannot accound for the entire risk as they are quite rare, (right?)
**Even though tumor suppressor genes are recessive on a cellular level, why are the phenotypes (the expression of cancer) effectively dominant?**