Reproductive Genetics 4 Flashcards

Recognize pedigree patterns consistent with hereditary gynecologic cancer syndromes.

1
Q

What are the major heritable gynecologic cancer syndromes?

A
  • BRCA1/BRCA2 (hereditary breast and ovarian cancer syndrome)
  • Lynch syndrome (Hereditary non-polyposis colorectal carcinoma)
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2
Q

What is the indication for doing genetic testing for hereditary cancer syndromes?

A
  • For carrier, positive status will impact surveillance recommendations
  • For non-carriers in families with mutation, avoids unecessary interventions
  • Risk-reducing surgery
  • Family members may be impacted
  • Reproductive decision-making
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3
Q

What are the BRCA1/2 mutations? What do they increase risk for?

A
  • Autosmal dominant, function as tumor suppressor genes
  • Heterozygous mutation = substantial increase in risk for early onset breast and/or ovarian cancer
  • “2nd hit” in remaining BRCA gene results in tumor formation
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4
Q

What are features that may indicate a BRCA1/2 mutation in a family?

A
  • Multiple cases early-onset breast cancer
  • Ovarian cancer, esp. early-onset
  • Breast and ovarian cancer in same patient
  • Bilateral breast cancer
  • Male breast cancer
  • Ashkenazi Jewish ancestry
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5
Q

What are the risks in individuals with BRCA1 mutations to develop cancer?

A
  • 85% lifetime risk for breast cancer, increases with age
    • 10% of women with breast cancer under 35 are carriers
  • 40% lifetime risk of ovarian cancer
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6
Q

What are the risks in individuals with BRCA2 mutations to develop cancer?

A
  • Lifetime breast cancer risk about 60%, up to 80%
  • Lifetime ovarian cancer risk 15-20%
  • Lifetime male breast cancer risk - 6%
    • 100 fold increase compared to general population
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7
Q

What are some methods to reduce risk of ovarian cancer in individuals with a BRCA mutation?

A
  • Birth control pills
  • First full-term pregnancy < age 25; number of pregnancies
  • Breast-feeding
  • BTL/hysterectomy RR 0.33/0.67
  • Prophylactic oophorectomy
    • Risk of primary peritoneal cancer remains
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8
Q

What is the epidemiology and genetics associated with lynch syndrome?

A
  • Defect in mismatch repair, mutation in one of the following
    • MLH1
    • MLH2
    • MSH6
    • PMS2
  • Results in microsatellite instability
  • Accounts for 1-6% of colorectal cancers and 2-3% of endometrial cancers
    • lifetime GI cancer risk is 90%
    • lifetime endometrial cancer risk is 60%
    • lifetime ovarian cancer risk is 15%
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9
Q

What are the clinical guidelines for diagnosis of Lynch syndrome, and what are the evaluation options for families with suspected mutations?

A
  • Amsterdam II criteria
    • At least 3 relatives with HNPCC-associated cancer
    • At least 2 successive generations affected
    • 1 affected is 1st-degree relative of the other 2
    • At least one of the malignancies diagnosed before age 50
  • Genetic evaluation
    • tumor testing for microsatellite instability
    • immunohistochemical testing of tumor
    • if positive, proceed to germline mutation testing
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10
Q

What is the surveillance protocol in an individual with Lynch syndrome?

A
  • Colonoscopy every 1-2 years beginning at 25
  • Endometrial/ovarian screening every year starting at 25-35
  • Prophylactic surgery may be option for patient
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