Cancer Genetics & Hereditary Syndromes Flashcards

A woman with a pathogenic BRCA1 variant asks about risk-reducing options. Which of the following has the greatest evidence for reducing ovarian cancer mortality?

Answer: Risk-reducing salpingo-oophorectomy (RRSO)

RRSO is the most effective intervention for reducing ovarian cancer risk and mortality in BRCA1 carriers, typically recommended between ages 35–40.

Tumor testing for microsatellite instability (MSI) or mismatch repair (MMR) protein expression via immunohistochemistry (IHC) is recommended for:

Answer: All patients diagnosed with colorectal cancer

Universal tumor testing for MSI/MMR is recommended for all colorectal cancer patients to identify those who may have Lynch syndrome.

Familial adenomatous polyposis (FAP) is caused by pathogenic variants in the APC gene and is characterized by:

Answer: Hundreds to thousands of colonic adenomatous polyps with near-100% colorectal cancer risk if untreated

Classic FAP involves hundreds to thousands of colorectal adenomas and carries essentially 100% lifetime risk of colorectal cancer without prophylactic colectomy.

Which PTEN-related syndrome is associated with an increased risk of breast, thyroid, endometrial, and colorectal cancers along with macrocephaly?

Answer: Cowden syndrome (PTEN hamartoma tumor syndrome)

Cowden syndrome, caused by germline PTEN pathogenic variants, presents with multiple hamartomas, macrocephaly, and elevated risks for breast, thyroid, and endometrial cancers.

A 28-year-old woman is referred after her mother was diagnosed with ovarian cancer. BRCA1/2 testing is BEST initiated with:

Answer: The affected mother first to identify the familial variant before testing unaffected relatives

Testing the affected individual first is optimal to identify the specific familial variant; if none is found, uninformative results in unaffected relatives are less meaningful.

Which of the following cancers is part of the Lynch syndrome cancer spectrum?

Answer: Endometrial, ovarian, gastric, urinary tract, and small bowel cancers

Lynch syndrome increases risk for a broad spectrum including endometrial, ovarian, gastric, urinary tract, small bowel, and other cancers beyond colorectal.