Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers

Johannes A. Rijken; Leonie van Hulsteijn; Olaf M. Dekkers; Nicolasine D. Niemeijer; C. Rene Leemans; Karin Eijkelenkamp; Anouk N. A. van der Horst-Schrivers; Michiel N. Kerstens; Anouk van Berkel; Henri J. L. M. Timmers; Henricus P. M. Kunst; Peter H. L. T. Bisschop; Koen M. A. Dreijerink; Marieke F. van Dooren; Frederik J. Hes; Jeroen C. Jansen; Eleonora P. M. Corssmit; Erik F. Hensen

doi:10.3390/cancers11010103

Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers

Johannes A. Rijken^*, Leonie van Hulsteijn, Olaf M. Dekkers, Nicolasine D. Niemeijer, C. Rene Leemans, Karin Eijkelenkamp, Anouk N. A. van der Horst-Schrivers, Michiel N. Kerstens, Anouk van Berkel, Henri J. L. M. Timmers, Henricus P. M. Kunst, Peter H. L. T. Bisschop, Koen M. A. Dreijerink, Marieke F. van Dooren, Frederik J. Hes, Jeroen C. Jansen, Eleonora P. M. Corssmit, Erik F. Hensen

^*Corresponding author for this work

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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.

Original language	English
Article number	103
Number of pages	11
Journal	Cancers
Volume	11
Issue number	1
DOIs	https://doi.org/10.3390/cancers11010103
Publication status	Published - 17-Jan-2019

Keywords

SDHB
SDHD
mortality
paraganglioma
pheochromocytoma
MUTATION CARRIERS
PARAGANGLIOMA
PHEOCHROMOCYTOMA
PENETRANCE
PHENOTYPE
HEAD

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Rijken, J. A., van Hulsteijn, L., Dekkers, O. M., Niemeijer, N. D., Leemans, C. R., Eijkelenkamp, K., van der Horst-Schrivers, A. N. A., Kerstens, M. N., van Berkel, A., Timmers, H. J. L. M., Kunst, H. P. M., Bisschop, P. H. L. T., Dreijerink, K. M. A., van Dooren, M. F., Hes, F. J., Jansen, J. C., Corssmit, E. P. M., & Hensen, E. F. (2019). Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers. Cancers, 11(1), Article 103. https://doi.org/10.3390/cancers11010103

@article{8b91257f400f4476b128cbea8fcf9ee8,

title = "Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers",

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, MUTATION CARRIERS, PARAGANGLIOMA, PHEOCHROMOCYTOMA, PENETRANCE, PHENOTYPE, HEAD",

author = "Rijken, {Johannes A.} and {van Hulsteijn}, Leonie and Dekkers, {Olaf M.} and Niemeijer, {Nicolasine D.} and Leemans, {C. Rene} and Karin Eijkelenkamp and {van der Horst-Schrivers}, {Anouk N. A.} and Kerstens, {Michiel N.} and {van Berkel}, Anouk and Timmers, {Henri J. L. M.} and Kunst, {Henricus P. M.} and Bisschop, {Peter H. L. T.} and Dreijerink, {Koen M. A.} and {van Dooren}, {Marieke F.} and Hes, {Frederik J.} and Jansen, {Jeroen C.} and Corssmit, {Eleonora P. M.} and Hensen, {Erik F.}",

year = "2019",

month = jan,

day = "17",

doi = "10.3390/cancers11010103",

language = "English",

volume = "11",

journal = "Cancers",

issn = "2072-6694",

publisher = "MDPI AG",

number = "1",

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Rijken, JA, van Hulsteijn, L, Dekkers, OM, Niemeijer, ND, Leemans, CR, Eijkelenkamp, K , van der Horst-Schrivers, ANA , Kerstens, MN, van Berkel, A, Timmers, HJLM, Kunst, HPM, Bisschop, PHLT, Dreijerink, KMA, van Dooren, MF, Hes, FJ, Jansen, JC, Corssmit, EPM & Hensen, EF 2019, 'Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers', Cancers, vol. 11, no. 1, 103. https://doi.org/10.3390/cancers11010103

TY - JOUR

T1 - Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers

AU - Rijken, Johannes A.

AU - van Hulsteijn, Leonie

AU - Dekkers, Olaf M.

AU - Niemeijer, Nicolasine D.

AU - Leemans, C. Rene

AU - Eijkelenkamp, Karin

AU - van der Horst-Schrivers, Anouk N. A.

AU - Kerstens, Michiel N.

AU - van Berkel, Anouk

AU - Timmers, Henri J. L. M.

AU - Kunst, Henricus P. M.

AU - Bisschop, Peter H. L. T.

AU - Dreijerink, Koen M. A.

AU - van Dooren, Marieke F.

AU - Hes, Frederik J.

AU - Jansen, Jeroen C.

AU - Corssmit, Eleonora P. M.

AU - Hensen, Erik F.

PY - 2019/1/17

Y1 - 2019/1/17

N2 - 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.

AB - 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.

KW - SDHB

KW - SDHD

KW - mortality

KW - paraganglioma

KW - pheochromocytoma

KW - MUTATION CARRIERS

KW - PARAGANGLIOMA

KW - PHEOCHROMOCYTOMA

KW - PENETRANCE

KW - PHENOTYPE

KW - HEAD

U2 - 10.3390/cancers11010103

DO - 10.3390/cancers11010103

M3 - Article

SN - 2072-6694

VL - 11

JO - Cancers

JF - Cancers

IS - 1

M1 - 103

ER -

Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers

Abstract

Keywords

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