Patients Tested at a Laboratory for Hereditary Cancer Syndromes Show an Overlap for Multiple Syndromes in Their Personal and Familial Cancer Histories

Abstract

Objective: Hereditary cancer testing guidelines are based on the premise that the common hereditary cancer syndromes have distinct, recognizable phenotypes. However, many syndromes present with overlapping cancers. The aim of this analysis was to identify the proportion of patients tested for Lynch syndrome (LS) or hereditary breast and ovarian cancer (HBOC) who met testing criteria for the other syndrome. Method: We analyzed a commercial laboratory database of patients tested for LS and HBOC in a clinical setting from 2006 to 2013. Patient cancer histories were analyzed using the 2012 NCCN criteria for LS and the 2013 NCCN criteria for HBOC. Results: In all, 7% of the patients tested for HBOC met criteria for LS testing. The majority of these patients had a family history of colorectal (30.9%) and/or endometrial cancer (22.7%). Conversely, 29.5% of the patients tested for LS met criteria for HBOC testing. In this group, 30.5% of the patients had a personal history of breast cancer, and 12.6% had a personal history of ovarian cancer. Conclusions: Our data demonstrate a substantial phenotypic overlap among patients for multiple common inherited cancer syndromes, which likely complicates diagnosis and test selection. This supports the value of multigene panels to identify pathogenic mutations in the absence of a clinically specific phenotype.

Detection of somatic variants in peripheral blood lymphocytes using a next generation sequencing multigene pan cancer panel

“…Given the significant phenotypic overlap of many hereditary cancer syndromes, NGS panels enable the simultaneous analysis of multiple genes associated with increased cancer risks (1,(10)(11)(12)(13)(14). This enables medical management decisions to be informed by gene-specific guidelines based on known risks associated with germline variants.…”

Inherited Cancer in the Age of Next-Generation Sequencing

“…Overlapping phenotypes and complex guidelines may lead to patients being missed with the traditional single-gene testing approach. In a study of 9,000 individuals referred for hereditary cancer testing, 30% of patients tested for Lynch syndrome also met criteria for HBOC testing, and inversely, 7% of patients sent for HBOC testing also met criteria for Lynch syndrome testing (Saam et al, 2015). Multigene tests may offer a simplified and efficient option for clinicians needing to select appropriate genes for a given patient.…”

CZECANCA: CZEch CAncer paNel for Clinical Application – Design and Optimization of the Targeted Sequencing Panel for the Identification of Cancer Susceptibility in High-risk Individuals from the Czech Republic

“…Zbytek případů připadá na mutace v desítkách až stovkách dalších genů, z nichž jen ně kte ré jsou dnes dobře charakterizovány, a případy hereditárního onemocnění na předpokládaném podkladě polygenní dědičnosti [2]. V porovnání s mutacemi v hlavních predispozičních genech se patogenní varianty v těchto dalších predispozičních genech vyznačují nižší penetrancí [3,4], nádorový tropizmus u postižení konkrétního genu je méně vyhraněný [5], vyskytují se s významně nižší populační frekvencí a tato frekvence je mnohdy významně proměnlivá v jednotlivých populacích a etnikách [6]. Identifi kace nosičů patogenních variant mimo oblast "klasických", vysoce penetrantních genů je tak tradičními genetickými postupy analyzujícími jednotlivé geny velmi nákladná a zdlouhavá.…”