King Hussein Cancer Center, Amman, Jordan
Hikmat Abdel-Razeq , Sarah M. Nielsen , Abdelghani Tbakhi , Hira Bani Hani , Baha' Sharaf , Ramiz Abu Hijlih , Mais Alkyam , Khansa Al-Azzam , Shatha Elemian , Areej Al-Atary , Malek Horani , Zeidan Zeidan , Abdulla Alzibdeh , Emily M. Russell , Brandie Heald , Robert Luke Nussbaum , Edward D. Esplin
Background: Germline genetic testing (GGT) has a significant impact on cancer care. While universal testing has been selectively implemented in the U.S., less is known about adoption of this approach in other ethnic groups. This study reports on GGT results among newly diagnosed cancer patients (pts) in Jordan. Methods: Jo-ECAG was a prospective study of newly diagnosed cancer pts between April 2021 and September 2022 who underwent 84 gene GGT. Patients were classified based on the 2020 National Comprehensive Cancer Network (NCCN) GGT criteria as meeting (in criteria, IC) or not meeting criteria (out of criteria, OOC). Demographics and clinical history were clinician-provided. Pts who were carriers for autosomal recessive conditions were excluded from pathogenic germline variant (PGV) count. Differences in proportions were determined using two-tailed Fisher’s exact test and the significance was set at p≤ 0.05. Results: The cohort consisted of 3,313 Arabic cancer pts, predominantly female (69.8%), with a median age of 54 at testing. Breast was the most commonly diagnosed cancer (50.4%), followed by colorectal (14.9%) and prostate (14.3%). 52% of pts tested were guidelines-based (IC). 460 PGVs were identified in 426 (12.9%) pts. PGVs were most commonly identified in APC (predominantly I1307K variant, 144 pts, 4.4%), BRCA2 (72, 2.2%), BRCA1 (36, 1.1%), CHEK2 (26, 0.8%) and ATM (25, 0.8%). While IC pts were more likely than OOC pts to have a PGV (15.7% vs 9.8%, p<0.0001), 156 (36.6%) pts with PGVs were OOC. 232 (54.5%) pts had PGVs in DNA damage response and repair/homologous recombination repair (DDR/HRR) genes, including 61 (26.3%) OOC pts. 3,602 variants of uncertain significance (VUS) were identified in 2,199 (66.4%) pts with 1,868 of these pts having only VUS results (56.4%), but the frequency in the latter group was not different between IC and OOC pts (p=0.42). Conclusions: Universal GGT of all new cancer pts was successfully implemented and led to actionable findings that would have been missed with guidelines-based testing. With the exception of an overrepresentation of APC I1307K variants, PGV rates were similar to Western ethnic groups. Over half of pts had PGVs in DDR/HRR genes that confer potential eligibility for targeted therapies and/or clinical trials. While VUS rates were high, they were similar between IC and OOC pts. Additional efforts to sequence underrepresented populations and develop variant interpretation methods agnostic to ancestry may help to mitigate these disparities.
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Abstract Disclosures
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