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Fumarate Hydratase Variants and Their Association With Paraganglioma/Pheochromocytoma.
Zavoshi, Shirin; Lu, Eric; Boutros, Paul C; Zhang, Liying; Harari, Avital; Hatchell, Kathryn E; Nielsen, Sarah M; Esplin, Edward D; Ouyang, Karen; Nykamp, Keith; Wilde, Blake; Christofk, Heather; Shuch, Brian.
Affiliation
  • Zavoshi S; Department of Internal Medicine, Ascension St. John Hospital, Detroit, MI; Institute of Urologic Oncology, University of California, Los Angeles, Los Angeles, CA.
  • Lu E; Division of Hematology/Oncology, University of California, Los Angeles, Los Angeles, CA.
  • Boutros PC; Institute of Urologic Oncology, University of California, Los Angeles, Los Angeles, CA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA; Departments of Human Genetics and Urology, University of California, Los Angeles, CA.
  • Zhang L; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Harari A; Division of Endocrine Surgery, Department of Surgery, University of California, Los Angeles, Los Angeles, CA.
  • Hatchell KE; Invitae, San Francisco, CA.
  • Nielsen SM; Invitae, San Francisco, CA.
  • Esplin ED; Invitae, San Francisco, CA.
  • Ouyang K; Invitae, San Francisco, CA.
  • Nykamp K; Invitae, San Francisco, CA.
  • Wilde B; Department of Biologic Chemistry, University of California, Los Angeles, Los Angeles, CA.
  • Christofk H; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA; Department of Biologic Chemistry, University of California, Los Angeles, Los Angeles, CA.
  • Shuch B; Institute of Urologic Oncology, University of California, Los Angeles, Los Angeles, CA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA. Electronic address: bshuch@mednet.ucla.edu.
Urology ; 176: 106-114, 2023 Jun.
Article in En | MEDLINE | ID: mdl-36773955
ABSTRACT

OBJECTIVE:

To clarify the link between germline variants in fumarate hydratase (FH), hereditary leiomyomatosis and renal cell cancer (HLRCC), and paraganglioma (PGL) and pheochromocytoma (PCC) we utilize a well-annotated hereditary cancer testing database.

METHODS:

Records of 120,061 patients receiving germline testing were obtained. FH variants were classified into 4 categories autosomal dominant (AD) HLRCC variants, autosomal recessive (AR) fumarase deficiency (FMRD), variants, previously reported as PGL/PCC FH variants, and variants of unknown significance (VUS) not previously associated with PGL/PCC (NPP-VUS). Rates of PGL/PCC were compared with those with negative genetic testing.

RESULTS:

About 1.3% of individuals carried FH variants which were more common among individuals with PGL/PCC compared to those without (3.1% vs 1.3%, P < .0001). PGL/PCC rates were higher among individuals with PGL/PCC FH variants compared to those with negative genetic testing (22.2% vs 0.9%, P < .0001). Neither AD HLRCC variants (0.3% vs 0.9%, P = .35) nor AR FMRD variants (1.4% vs 0.9%, P = .19) carried an increased prevalence of PGL/PCC. An increased prevalence of PGL/PCC was detected in those with NPP-VUS (2.0% vs 0.9%, P = .0023).

CONCLUSIONS:

Certain FH variants confer an increased risk of PGL/PCC, but not necessarily HLRCC. While universal screening for PGL/PCC among all individuals with FH variants does not appear warranted, it should be considered in select high-risk PGL/PCC FH variants.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Paraganglioma / Pheochromocytoma / Skin Neoplasms / Uterine Neoplasms / Adrenal Gland Neoplasms Type of study: Risk_factors_studies Limits: Female / Humans Language: En Journal: Urology Year: 2023 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Paraganglioma / Pheochromocytoma / Skin Neoplasms / Uterine Neoplasms / Adrenal Gland Neoplasms Type of study: Risk_factors_studies Limits: Female / Humans Language: En Journal: Urology Year: 2023 Document type: Article Affiliation country: