Risks of Other Cancers in BRCA1BRCA2 Carriers

In addition to the marked excess of breast and ovarian cancer in BRCA1 and BRCA2 carriers, there is also evidence of more moderate risks of other cancer types. The largest study of cancer risks in BRCA1 carriers, based on 699 carrier families, found an overall cancer risk in male carriers very close to that in the general population, but the risk of cancers other than breast or ovarian in female carriers was increased by approximately twofold (44). Specifically, significant excesses were seen for cancers of the corpus uteri, the cervix, the fallopian tubes, and the peritoneum. There was also some evidence of a twofold relative risk of pancreatic cancer in carriers of both sexes and prostate cancer below age 65.

In a parallel study based on 173 BRCA2 families, the risk of other cancers was approximately twofold in both male and female carriers (42). The largest excess risk was for prostate cancer, with an estimated 4.7-fold relative risk, increasing to sevenfold in men below age 65. A 3.5-fold risk of pancreatic cancer was also found, and significant excesses were also seen for cancers of the stomach, buccal cavity and pharynx, gallbladder and bile duct, and fallopian tube and for melanoma. A more recent study from the Netherlands also found increased risks of prostate, pancreatic cancer, and head and neck cancer (43).

Other studies have also demonstrated an association between prostate cancer and BRCA2 mutations. For example, two Icelandic studies found relative risks of prostate cancer between three and five among the first-degree relatives of BRCA2 mutation carriers (58,59). In addition, a study of 263 prostate cancer cases diagnosed below age 56 years, unselected for family history, estimated a BRCA2 carrier frequency of nearly 3% (60).

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