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Cancers (Basel). 2019 Jan 17;11(1). pii: E103. doi: 10.3390/cancers11010103.

Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers.

Author information

1
Department of Otolaryngology/Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands. j.rijken@vumc.nl.
2
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands. lvanhulsteijn@hotmail.com.
3
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands. O.M.Dekkers@lumc.nl.
4
Departments of Epidemiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands. O.M.Dekkers@lumc.nl.
5
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands. nniemeijer@ysl.nl.
6
Department of Otolaryngology/Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands. cr.leemans@vumc.nl.
7
Department of Endocrinology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. k.eijkelenkamp@umcg.nl.
8
Department of Endocrinology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. a.n.a.van.der.horst@umcg.nl.
9
Department of Endocrinology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. m.n.kerstens@umcg.nl.
10
Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands. anouk.vanberkel@radboudumc.nl.
11
Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands. henri.timmers@radboudumc.nl.
12
Department of Otolaryngology/Head and Neck Surgery, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands. dirk.kunst@radboudumc.nl.
13
Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. p.h.bisschop@amc.uva.nl.
14
Department of Endocrinology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. k.dreijerink@vumc.nl.
15
Department of Endocrinology, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands. k.dreijerink@vumc.nl.
16
Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. m.vandooren@erasmusmc.nl.
17
Department of Clinical Genetics, Leiden University Medical Center, De Boelelaan 1117, 1081 HZ Leiden, The Netherlands. F.J.Hes@lumc.nl.
18
Department of Otolaryngology/Head and Neck Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. j.c.jansen@lumc.nl.
19
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands. E.P.M.van_der_Kleij-Corssmit@lumc.nl.
20
Department of Otolaryngology/Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands. E.F.Hensen@lumc.nl.
21
Department of Otolaryngology/Head and Neck Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. E.F.Hensen@lumc.nl.

Abstract

Germline mutations in succinate dehydrogenase subunit B and D (SDHB and SDHD) are predisposed to hereditary paraganglioma (PGL) and pheochromocytoma (PHEO). The phenotype of pathogenic variants varies according to the causative gene. In this retrospective study, we estimate the mortality of a nationwide cohort of SDHB variant carriers and that of a large cohort of SDHD variant carriers and compare it to the mortality of a matched cohort of the general Dutch population. A total of 192 SDHB variant carriers and 232 SDHD variant carriers were included in this study. The Standard Mortality Ratio (SMR) for SDHB mutation carriers was 1.89, increasing to 2.88 in carriers affected by PGL. For SDHD variant carriers the SMR was 0.93 and 1.06 in affected carriers. Compared to the general population, mortality seems to be increased in SDHB variant carriers, especially in those affected by PGL. In SDHD variant carriers, the mortality is comparable to that of the general Dutch population, even if they are affected by PGL. This insight emphasizes the significance of DNA-testing in all PGL and PHEO patients, since different clinical risks may warrant gene-specific management strategies.

KEYWORDS:

SDHB; SDHD; mortality; paraganglioma; pheochromocytoma

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