Moukadem HA, Fakhreddine MA, Assaf N, Safi N, Al Masry A, Al Darazi M, Mahfouz R, El Saghir NS. Germline pathogenic variants among high hereditary risk patients with breast and ovarian cancer and unaffected subjects in Lebanese Arab women. World J Clin Oncol 2024; 15(12): 1481-1490 [DOI: 10.5306/wjco.v15.i12.1481]
Corresponding Author of This Article
Nagi S El Saghir, MD, Professor, Division of Hematology Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Cairo Street, PO Box 11-0236, Riad El Solh, Beirut 1107 2020, Lebanon. ns23@aub.edu.lb
Research Domain of This Article
Oncology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Dec 24, 2024; 15(12): 1481-1490 Published online Dec 24, 2024. doi: 10.5306/wjco.v15.i12.1481
Germline pathogenic variants among high hereditary risk patients with breast and ovarian cancer and unaffected subjects in Lebanese Arab women
Hiba A Moukadem, Mohammad A Fakhreddine, Nada Assaf, Nadine Safi, Ahmad Al Masry, Monita Al Darazi, Rami Mahfouz, Nagi S El Saghir
Hiba A Moukadem, Mohammad A Fakhreddine, Nadine Safi, Ahmad Al Masry, Monita Al Darazi, Nagi S El Saghir, Division of Hematology/Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon
Nada Assaf, Rami Mahfouz, Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut 1001, Lebanon
Author contributions: El Saghir NS was responsible for conception and design and administrative support; Mahfouz R and El Saghir NS were responsible for provision of study materials or patients; Moukadem HA, Fakhreddine MA, Assaf N, Safi N, Al Masry A, Al-Darazi MH and El Saghir NS were responsible for collection and assembly of data; Moukadem HA, Fakhreddine MA, Assaf N and El Saghir NS were responsible for data analysis and interpretation; Moukadem HA, Fakhreddine MA, Assaf N, Safi N, Al Masry A, Al Darazi M, Mahfouz R and El Saghir NS were responsible for manuscript writing and final approval of manuscript; all of the authors read and approved the final version of the manuscript to be published.
Institutional review board statement: The study was reviewed and approved by the Institutional Review board at the American University of Beirut Medical Center.
Informed consent statement: No consent form was required since patients were not approached.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Data sharing statement: Study data are available upon request from the corresponding author.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Nagi S El Saghir, MD, Professor, Division of Hematology Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Cairo Street, PO Box 11-0236, Riad El Solh, Beirut 1107 2020, Lebanon. ns23@aub.edu.lb
Received: July 10, 2024 Revised: August 23, 2024 Accepted: October 11, 2024 Published online: December 24, 2024 Processing time: 103 Days and 11.8 Hours
Abstract
BACKGROUND
The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries.
AIM
To determine the prevalence of germline pathogenic variants in high hereditary risk patients with breast and/or ovarian cancer and unaffected individuals.
METHODS
We retrospectively reviewed records of patients and unaffected subjects referred for germline pathogenic variant testing due to high hereditary risk between 2010-2020. Data was collected and analyzed on Excel sheet.
RESULTS
In total, 358 individuals were included, including 257 patients and 101 unaffected individuals with relatives with breast or ovarian cancer. The prevalence of breast cancer susceptibility gene (BRCA) 1/2 pathogenic variants was 8.63% (19/220) in patients with breast cancer, and 15.1% (5/33) in those with ovarian cancer. Among the 25 of 220 patients with breast cancer tested by next-generation sequencing, 3 patients had pathogenic variants other than BRCA1/2. The highest risk was observed in those aged 40 years with breast cancer and a positive family history, where the BRCA1/2 prevalence was 20.1% (9/43). Among the unaffected subjects, 31.1% (14/45) had the same BRCA1/2 pathogenic variants in their corresponding relatives. Among the subjects referred because of a positive family history of cancer without known hereditary factors, 5.35% (3/56) had pathogenic variants of BRCA1 and BRCA2. The c.131G>T nucleotide change was noted in one patient and two unrelated unaffected subjects with a BRCA1 pathogenic variant.
CONCLUSION
This study showed a 8.63% prevalence of pathogenic variants in patients with breast cancer and a 15.1% prevalence in patients with ovarian cancer. Among the relatives of patients with BRCA1/2 pathogenic variants, 31% tested positive for the same variant, while 5.3% of subjects who tested positive due to a family history of breast cancer had a BRCA pathogenic variant.
Core Tip: This is the first study on referred patients with breast and/or ovarian cancer and subjects at high hereditary risk for germline pathogenic variant testing among ethnic Lebanese Arab women. The prevalence of pathogenic variants was 8.63% in patients with breast cancer and 15.1% in patients with ovarian cancer. Among the relatives of patients with breast cancer susceptibility gene (BRCA) 1/2 pathogenic variants, 31% tested positive for the same variant, while 5.3% of subjects who tested positive due to a family history of breast cancer had a BRCA pathogenic variant. The results of this study support the hypothesis that the c.131G>T nucleotide change is a founder pathogenic variant in this population.
