TY - JOUR
T1 - Germline BRCA1/BRCA2 mutations among high risk breast cancer patients in Jordan
AU - Abdel-Razeq, Hikmat
AU - Al-Omari, Amal
AU - Zahran, Farah
AU - Arun, Banu
N1 - Funding Information:
The study was funded by a competitive grant from the King Hussein Cancer Center/MD Anderson Cancer Center Sister Institution Network Fund (SINF). The study was approved by King Hussein Cancer Center Institutional Review Board (IRB) under project number 11KHCC63. All patients signed informed consent.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/2/6
Y1 - 2018/2/6
N2 - Background: Breast cancer is the most common malignancy and the leading cause of cancer-related deaths among Jordanian women. With a median age of 50 years at diagnosis, a higher prevalence of hereditary breast cancer may be expected. The objective of this pilot study is to evaluate, for the first time, the contribution of germline mutations in BRCA1/2 to breast cancer among Jordanian patients. Methods: Jordanian breast cancer women with a selected high risk profile were invited to participate. Peripheral blood samples were obtained for DNA extraction. A detailed 3-generation family history was also collected. BRCA sequencing was performed at a reference laboratory. Mutations were classified as deleterious, suspected deleterious, variant of uncertain significance or favor polymorphisms. Patients' medical records were reviewed for extraction of clinical and tumor pathology data. Results: One hundred patients were enrolled to the study. Median age was 40 (22-75) years. In total, 20 patients had deleterious and 7 suspected deleterious mutations in BRCA1 or BRCA2 genes. Seven variants of uncertain significance were also detected. After excluding patients tested subsequent to the index case in their families, highest mutation rates were observed among triple negatives (9/16, 56.3%) especially among those with positive family history of breast and/or ovarian cancer (9/13, 69.2%), patients with bilateral or second primary breast cancer (10/15, 66.7%) and those with family history of male breast cancer (2/5, 40.0%). Conclusions: BRCA1/2 mutations are not uncommon among selected Jordanian females with breast cancer. The contribution of these findings to much younger age at diagnosis is debatable. Although small, our selected patient cohort shows an important incidence of deleterious and suspected deleterious BRCA1/2 mutations suggesting that genetic testing should be offered to patients with certain high risk features.
AB - Background: Breast cancer is the most common malignancy and the leading cause of cancer-related deaths among Jordanian women. With a median age of 50 years at diagnosis, a higher prevalence of hereditary breast cancer may be expected. The objective of this pilot study is to evaluate, for the first time, the contribution of germline mutations in BRCA1/2 to breast cancer among Jordanian patients. Methods: Jordanian breast cancer women with a selected high risk profile were invited to participate. Peripheral blood samples were obtained for DNA extraction. A detailed 3-generation family history was also collected. BRCA sequencing was performed at a reference laboratory. Mutations were classified as deleterious, suspected deleterious, variant of uncertain significance or favor polymorphisms. Patients' medical records were reviewed for extraction of clinical and tumor pathology data. Results: One hundred patients were enrolled to the study. Median age was 40 (22-75) years. In total, 20 patients had deleterious and 7 suspected deleterious mutations in BRCA1 or BRCA2 genes. Seven variants of uncertain significance were also detected. After excluding patients tested subsequent to the index case in their families, highest mutation rates were observed among triple negatives (9/16, 56.3%) especially among those with positive family history of breast and/or ovarian cancer (9/13, 69.2%), patients with bilateral or second primary breast cancer (10/15, 66.7%) and those with family history of male breast cancer (2/5, 40.0%). Conclusions: BRCA1/2 mutations are not uncommon among selected Jordanian females with breast cancer. The contribution of these findings to much younger age at diagnosis is debatable. Although small, our selected patient cohort shows an important incidence of deleterious and suspected deleterious BRCA1/2 mutations suggesting that genetic testing should be offered to patients with certain high risk features.
KW - BRCA1
KW - BRCA2
KW - Breast cancer
KW - Hereditary breast cancer
KW - Jordan
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U2 - 10.1186/s12885-018-4079-1
DO - 10.1186/s12885-018-4079-1
M3 - Article
C2 - 29409476
AN - SCOPUS:85041394745
SN - 1471-2407
VL - 18
JO - BMC cancer
JF - BMC cancer
IS - 1
M1 - 152
ER -