{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T12:41:37Z","timestamp":1776084097511,"version":"3.50.1"},"reference-count":27,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"5","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precision Oncology"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> Whether individuals with monoallelic FH pathogenic variants (PVs) associated with autosomal recessive fumarate hydratase (FH) deficiency are also at risk of autosomal dominant FH-associated tumors is of paramount clinical importance. <\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p> A retrospective study of individuals with a PV in the FH gene identified via multigene panel testing from 2012 to 2019 through a single testing laboratory was performed. Cancer histories of individuals with PVs in FH ( FH PV) were compared to those with PVs associated only with autosomal recessive FH deficiency (FH-d PV) and to FH-negative controls. Cancer histories of individuals with truncating versus nontruncating FH PV were also compared. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> Individuals with FH PV were more likely to have kidney cancer than those with FH-d PV (odds ratio, 9.0; 95% CI, 4.4 to 20.0; P &lt; .001) or FH-negative controls (odds ratio, 7.6; 95% CI, 5.2 to 11.2; P value &lt; .001). The FH PV cohort had kidney cancer at a significantly younger age (median age: 35.0 years; interquartile range, 26.0-45.0 years) than the FH-d PV cohort (median age: 44.5 years; interquartile range, 43.5-53.5 years; P = .011). Within the FH PV cohort, there were no differences in the frequency or age at kidney cancer between those with truncating versus nontruncating PV. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> Unlike FH PV, FH-d PV are not associated with kidney cancers at early ages of onset. The FH-d PV cohort had a cancer phenotype that resembled FH-negative controls. These data may inform genetic counseling and risk assessment of individuals with FH-d PV. <\/jats:p><\/jats:sec>","DOI":"10.1200\/po.21.00263","type":"journal-article","created":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T22:49:03Z","timestamp":1633560543000},"page":"1568-1578","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":8,"title":["Different Fumarate Hydratase Gene Variants Are Associated With Distinct Cancer Phenotypes"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2852-7387","authenticated-orcid":false,"given":"Junne","family":"Kamihara","sequence":"first","affiliation":[{"name":"Dana-Farber\/Boston Children's Cancer and Blood Disorders Center, Boston, MA"},{"name":"Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA"},{"name":"Harvard Medical School, Boston, 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