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Much remains elusive in our understanding of cancer susceptibility. Breast
cancer is a good example of how incomplete a picture we have.
Most women with a family history of breast cancer DO NOT carry germline
mutations in the single highly penetrant cancer susceptibility genes, yet
familial clusters continue to appear with each new generation.
About 5 to 10 percent of breast cancer cases are linked to germline mutations
in single, highly penetrant cancer susceptibility genes such as BRCA1 and
BRCA2. Strong genetic predisposition and cancer susceptibility in these
families is passed down in an autosomal dominant fashion.
Another 15 to 20 percent of breast cancers, however, are associated with some
family history but no evidence of such autosomal dominant transmission. These
cases are not well understood. Possibly environmental or multiple gene
interactions contribute to very low penetrance of susceptibility genes, or
possibly yet undiscovered mutations are involved.
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