(PQD3) Genetic Basis of Breast Cancer Resistance in BRCA1+ Carrier

描述（由申请人提供）：我们的提案解决了RFA-CA-12-022中的PQD 3：“哪些潜在因果事件-例如，遗传的、表观遗传的、生物的、行为的或环境的--允许某些个体生存超过否则高度致命的癌症的预期极限？“BRCA 1突变是乳腺癌最著名的遗传原因之一。在BRCA 1+家族中，高达80%的遗传了BRCA 1突变的家庭成员会在70岁时患上乳腺癌，而20%的遗传了BRCA 1突变的家庭成员（BRCA 1+携带者）是乳腺癌抵抗者，因为他们一生中不会患上乳腺癌。在这项提案中，我们计划研究乳腺癌抗性的遗传基础。我们计划使用外显子组测序方法来比较来自相同BRCA 1+家族的乳腺癌受影响和乳腺癌未受影响对之间的整个基因，以识别两种类型的家族成员之间不同突变的基因，并确定其与乳腺癌的功能相关性。我们的建议通过识别保护BRCA 1+个体免受乳腺癌的基因来直接解决PQD 3。

DESCRIPTION (provided by applicant): Our proposal addresses the PQD3 in the RFA-CA-12-022: "What underlying causal events - e.g., genetic, epigenetic, biologic, behavioral, or environmental - allow certain individuals to survive beyond the expected limits of otherwise highly lethal cancers?" BRCA1 mutation is one of the best-known genetic causes for breast cancer. In BRCA1+ families, up to 80% of the family members who inherited BRCA1 mutation will develop breast cancer by age of 70, whereas 20% of the family members who also inherited BRCA1 mutation (BRCA1+ carrier) are breast cancer-resistance in that they will never develop breast cancer in their lifetime. In this proposal, we plan to study the genetic basis of breast cancer-resistance. We plan to use exome sequencing method to compare the entire genes between the breast cancer-affected and breast cancer- unaffected pairs from the same BRCA1+ families to identify the genes mutated differently between the two types of family members and to determine their functional relevance to breast cancer. Our proposal directly addresses the PQD3 by identifying the genes that protect the BRCA1+ individuals from breast cancer.