Moein Kanaan, PhD

Increasing genetic screening and advancing the understanding of inherited risk factors in diverse populations.

Impact

The BRCA1 and BRCA2 genes are the two most common genes known to be associated with an increased risk of hereditary breast and ovarian cancer. When working correctly, BRCA1 and BRCA2 are tumor suppressor genes that protect the body from DNA errors that can lead to cancer. Mutations in the BRCA genes that causes them not to function correctly are highly prevalent among people of Ashkenazi Jewish (AJ) ancestry. Israel, which has a large AJ population, offers some of the best genetic screening and follow-up services in the world. However, screening and services have been lacking for Arab and Palestinian women. The Middle East Breast Cancer Study (MEBCS), led by BCRF Investigators Moein Kanaan, Ephrat Levy-Lahad, and Mary-Claire King, seeks to address this disparity.

Progress Thus Far

The goals of the MEBCS are to determine the genetic basis of inherited predisposition to breast cancer among Palestinian and Arab-Israeli women and to establish and develop the necessary infrastructure for cancer genetics services for women in this population. The MEBCS established and studies a cohort of breast cancer patients diagnosed at multiple Palestinian institutions and at Shaare Zedek Medical Center in Jerusalem, Israel. The cohort now comprises 1,457 Palestinian patients with invasive breast cancer and about 400 members of their families. This is the largest cohort in the Arab world for studies of inherited breast cancer. The team has found that the genetic basis of inherited breast cancer in Palestinians is highly heterogeneous, and they continue to identify novel mutations. They also identified two additional families with TP53 R181C, the founder mutation responsible for about one percent of breast cancer in Palestinian patients. The families harboring this mutation have high risk of young-onset breast cancer. Among all families from the cohort, breast cancer risk among carriers of TP53 R181C is 74 percent by age 70.

What’s next

In the upcoming year, the team will continue to recruit newly diagnosed Palestinian breast cancer patients into the cohort. Their results indicate that a very high level of diversity in genetic predisposition to breast cancer remains to be discovered in the Palestinian population. The team will also evaluate the recently identified new BRCA2 mutations, which have broad relevance to inherited breast cancer. Finally, they will further explore the cancer spectrum associated with the TP53 R181C mutation to determine the appropriate surveillance in these families. These results will have general implications for carriers of TP53 mutations identified through gene panel testing. By identifying and characterizing previously unknown genetic causes of breast cancer, their work will benefit breast cancer patients and their families in the Palestinian and Arab populations and worldwide.