Implementation of universal pan-cancer germline genetic testing in an Arab population: The jordanian exploratory cancer fenetics (Jo-ECAG) study.

Authors

Hikmat Abdel-Razeq

Hikmat Abdel-Razeq

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

Organizations

King Hussein Cancer Center, Amman, Jordan, Invitae, San Francisco, CA, King Hussein Medical Center, Amman, Jordan, Invitae, San Leandro, CA

Research Funding

Institutional Funding
Invitae, King Hussein Cancer Center

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 Details

Meeting

2023 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Prevention, Risk Reduction, and Hereditary Cancer

Track

Prevention, Risk Reduction, and Genetics

Sub Track

Germline Genetic Testing

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr 10591)

DOI

10.1200/JCO.2023.41.16_suppl.10591

Abstract #

10591

Poster Bd #

224

Abstract Disclosures

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