Posted on February 05, 2019
DICER1 Syndrome is an inherited disorder caused by pathogenic germline variants in the DICER1 gene. Individuals with this syndrome are at risk for multiple types of tumors, benign and malignant. Because the tumor outcomes are rare, researchers have been unable to quantify the risk/penetrance of these variants. A new study of >100 individuals with germline DICER1 pathogenic variants (DICER1-carriers) is the first to quantify those risks by tumor site. This study was published online February 4, 2019, in the Journal of Clinical Oncology.
While DICER1-associated tumors are rare, the germline pathogenic variants in DICER1 are more common than previously estimated – they occur in about one in 10,000 people in the general population. The findings were the product of a collaboration between DCEG investigators in the Clinical Genetics Branch and researchers at the International PPB/DICER1 Registry, utilizing data from three large cohorts: the International PPB/DICER1 Registry, the National Cancer Institute Natural History of DICER1 Syndrome study, and the International Ovarian and Testicular Stromal Tumor Registry.
The investigators determined the cumulative tumor incidence in non-proband DICER1-carriers, relatives of the proband (the patient initially diagnosed with a DICER1 Syndrome-associated tumor) without disease at time of the proband’s enrollment in the study. By age 10, 5.3 percent of non-proband DICER1-carriers had developed a neoplasm (females=4.0%; males=6.6%). After age 10, risk among females was elevated relative to risk among males. By age 50, nearly 20 percent of non-probands had developed a neoplasm (females=26.5%; males=10.2%). Overall, all DICER1-carriers experienced significant excesses in cancer risk, particularly for gynecologic and thyroid malignancies, compared to the general population. These findings may improve our understanding of the DICER1 Syndrome phenotype, natural history, genetic counseling, and tumor surveillance strategies.
Stewart D, Best A, Williams GM, Harney LA, Carr AG, Harris AK, et al. Neoplasm Risk Among Individuals With a Pathogenic Germline Variant in DICER1. Journal of Clinical Oncology, February 4, 2019. DOI: 10.1200/JCO.2018.78.4678 [Epub ahead of print]