Clinical genetic testing outcome with multi-gene panel in Asian patients with multiple primary cancers
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Gloria H.J. Chan1,*, Pei Yi Ong1,*, Jeffrey J.H. Low2, Hwai Loong Kong1, Samuel G.W. Ow1, David S.P. Tan1,3, Yi Wan Lim1, Siew Eng Lim1 and Soo-Chin Lee1,3
1Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), Singapore
2Department of Obstetrics and Gynaecology, National University Hospital, Singapore
3Cancer Science Institute, Singapore
*These authors have contributed equally to this work
Soo-Chin Lee, email: firstname.lastname@example.org
Keywords: genetic testing; germ-line mutation; neoplasms; multiple primary/diagnosis
Received: May 22, 2018 Accepted: June 23, 2018 Published: July 17, 2018
Background: Developing multiple cancers is an indicator of underlying hereditary cancer predisposition, but there is a paucity of data regarding the clinical genetic testing outcomes of these patients.
Methods: We compared cancer index patients with ≥2 primary malignancies versus 1 primary cancer who underwent clinical evaluation and testing with multi-gene panels comprising up to 49 genes from 1998-2016.
Results: Among 1191 cancer index patients, 80.6%, 17.2%, and 2.2% respectively had 1, 2, and ≥3 primary malignancies. For patients with 2 primary cancers (n=205), the most common cancer pairs were bilateral breast (37.5%), breast-ovary (11.7%), endometrium-ovary (9.2%), colon-endometrium (3.9%) and colon-colon (3.4%). 42.3% patients underwent gene testing including 110/231 (47.6%) with multiple malignancies. Pathogenic variants were found more frequently in younger patients, in those with a family history of cancer related to the suspected syndrome, and a trend towards significance in those with multiple primary cancers (35.5% vs. 25.6%, p = 0.09). In patients with multiple cancers, pathogenic variants were most commonly identified in BRCA1 (38.5%), BRCA2 (17.9%), and the mismatch repair genes (20.5%), while 23.1% of pathogenic mutations were in other moderate- to high-penetrance cancer predisposition genes including APC, ATM, MUTYH, PALB2, RAD50 and TP53.
Conclusion: Patients with multiple cancers were more likely to carry pathogenic mutations than those with single cancer. About three-quarters of deleterious mutations in patients with multiple primary cancers were in BRCA1/2 and the mismatch repair genes, but multi-gene panel testing facilitated the detection of mutations in another 6 genes and is warranted in this high-risk population.
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