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. 2018 Jul 17;9(55):30649-30660.
doi: 10.18632/oncotarget.25769.

Clinical genetic testing outcome with multi-gene panel in Asian patients with multiple primary cancers

Gloria H J Chan  1 , Pei Yi Ong  1 , Jeffrey J H Low  2 , Hwai Loong Kong  1 , Samuel G W Ow  1 , David S P Tan  1   3 , Yi Wan Lim  1 , Siew Eng Lim  1 , Soo-Chin Lee  1   3
Affiliations

Clinical genetic testing outcome with multi-gene panel in Asian patients with multiple primary cancers

Gloria H J Chan et al. Oncotarget. .

Abstract

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.

Keywords: genetic testing; germ-line mutation; multiple primary/diagnosis; neoplasms.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1. Distribution of multiple primary cancers in patients with 2 primary cancers (n = 205)
Figure 2
Figure 2. Pathogenic variants identified
Figure 3
Figure 3. Variants of uncertain significance – Frequency per subject
Figure 4
Figure 4. Variants of uncertain significance – VUS count per gene
See this image and copyright information in PMC

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