Can a daughter be BRCA2 (Breast Cancer Gene 2) positive if her father's sister had a BRCA2 mutation but her father is BRCA2 negative?

BRCA2 Inheritance Patterns and Risk Assessment

No, if a father tests negative for a BRCA2 mutation, his daughter cannot inherit that specific BRCA2 mutation from him. 1

Understanding BRCA Inheritance

BRCA1 and BRCA2 mutations are inherited in an autosomal dominant pattern, meaning that only one copy of the mutated gene is needed to increase cancer risk 1. However, for a daughter to inherit a specific BRCA2 mutation:

• The mutation must be present in one of her parents
• If the father has tested negative for the specific BRCA2 mutation found in his sister (the patient's aunt), he cannot pass this mutation to his daughter

Key inheritance principles:

1. BRCA mutations follow Mendelian inheritance patterns
2. A negative test in the father means he did not inherit the mutation from his parents
3. Since the father doesn't carry the mutation, he cannot transmit it to his children

Genetic Testing Interpretation

When interpreting genetic test results in families with known mutations:

• A true-negative result occurs when a relative tests negative for a known family mutation 1
• This provides reassurance about inherited risk for that specific mutation
• The daughter in this case would be considered at population risk for breast cancer related to this specific BRCA2 mutation

Family Risk Assessment

Despite the father testing negative for the BRCA2 mutation:

• The family history should still be evaluated for other potential genetic factors
• Other high-risk breast cancer genes beyond BRCA1/2 may exist in some families 1
• The daughter's breast cancer risk should be assessed based on overall family history from both maternal and paternal sides

Common Pitfalls in Genetic Testing Interpretation

1. Misinterpreting negative results: A negative test in the father definitively rules out inheritance of that specific mutation, but doesn't eliminate all genetic risk 1

2. Focusing only on one side of the family: Cancer risk assessment should include maternal and paternal lineages 1

3. Overlooking other genetic factors: BRCA1/2 mutations account for only 20-30% of familial breast cancer clustering 1

4. Assuming all family cancer is related to one mutation: Multiple genetic factors can exist in families 1

Recommendations for Risk Management

For the daughter in this scenario:

• Her risk should be based on family history alone, not the aunt's BRCA2 mutation 1
• If there is no significant family history of breast/ovarian cancer on either side, her risk is similar to the general population 2
• Standard breast cancer screening according to general population guidelines would be appropriate
• Referral for genetic counseling may be warranted if there are other concerning aspects of family history

Conclusion

The biological principle is clear: if the father tested negative for the specific BRCA2 mutation found in his sister, his daughter cannot inherit that particular mutation from him. Her breast cancer risk assessment should be based on overall family history rather than her aunt's BRCA2 mutation status.