Abstract
BackgroundDeveloping 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.MethodsWe 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.ResultsAmong 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.ConclusionPatients 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.
Highlights
Developing multiple primary cancers may be due to a common exposure
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 moderateto high-penetrance cancer predisposition genes including APC, ATM, MUTYH, PALB2, RAD50 and TP53
Summary
Developing multiple primary cancers may be due to a common exposure (e.g., radiation, tobacco-smoking, papilloma virus or a susceptibility gene). International clinical practice guidelines advocate cancer genetic screening for patients with multiple primary cancers [1, 2]. There is still a paucity of data regarding the characteristics and clinical genetic testing outcome of patients with multiple primary cancers, in Asia. We describe the characteristics and genetic testing outcomes of patients with multiple versus single www.oncotarget.com primary cancers who were evaluated in a cancer genetics clinic in a tertiary cancer center in Asia. 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
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