CGC Cancer Genetics & Hereditary Syndromes 2 — Questions and Answers
Question 1: 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?
- Annual CA-125 and transvaginal ultrasound
- Risk-reducing salpingo-oophorectomy (RRSO) (Correct answer)
- Oral contraceptive use indefinitely
- Prophylactic whole-abdominal radiation
Correct 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.
Question 2: Tumor testing for microsatellite instability (MSI) or mismatch repair (MMR) protein expression via immunohistochemistry (IHC) is recommended for:
- All patients with breast cancer
- All patients diagnosed with colorectal cancer (Correct answer)
- Patients over age 70 with any cancer
- Patients with no family history of cancer
Correct 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.
Question 3: Familial adenomatous polyposis (FAP) is caused by pathogenic variants in the APC gene and is characterized by:
- A few colonic polyps (fewer than 10) in adulthood
- Hundreds to thousands of colonic adenomatous polyps with near-100% colorectal cancer risk if untreated (Correct answer)
- Hamartomatous polyps throughout the GI tract
- Exclusively upper GI polyps with low malignant potential
Correct 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.
Question 4: Which PTEN-related syndrome is associated with an increased risk of breast, thyroid, endometrial, and colorectal cancers along with macrocephaly?
- Bannayan-Riley-Ruvalcaba syndrome
- Cowden syndrome (PTEN hamartoma tumor syndrome) (Correct answer)
- Peutz-Jeghers syndrome
- Juvenile polyposis syndrome
Correct 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.
Question 5: A 28-year-old woman is referred after her mother was diagnosed with ovarian cancer. BRCA1/2 testing is BEST initiated with:
- The 28-year-old patient directly since she is at risk
- The affected mother first to identify the familial variant before testing unaffected relatives (Correct answer)
- The patient's siblings simultaneously
- Population-based BRCA testing without family history context
Correct 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.
Question 6: Which of the following cancers is part of the Lynch syndrome cancer spectrum?
- Pancreatic cancer exclusively
- Endometrial, ovarian, gastric, urinary tract, and small bowel cancers (Correct answer)
- Medullary thyroid cancer
- Mesothelioma
Correct 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.
CGC Cancer Genetics & Hereditary Syndromes 2
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?