Single-nucleotide polymorphism in the 5-alpha-reductase gene (SRD5A2) is associated with increased prevalence of metabolic syndrome in chemotherapy-treated testicular cancer survivors

Hink Boer; Nico-Derk L. Westerink; Renske Altena; Janine Nuver; D. A. Janneke Dijck-Brouwer; Martijn van Faassen; Frank Klont; Ido P. Kema; Joop D. Lefrandt; Nynke Zwart; H. Marike Boezen; Andries J. Smit; Coby Meijer; Jourik A. Gietema

doi:10.1016/j.ejca.2015.11.009

Single-nucleotide polymorphism in the 5-alpha-reductase gene (SRD5A2) is associated with increased prevalence of metabolic syndrome in chemotherapy-treated testicular cancer survivors

Hink Boer, Nico-Derk L. Westerink, Renske Altena, Janine Nuver, D. A. Janneke Dijck-Brouwer, Martijn van Faassen, Frank Klont, Ido P. Kema, Joop D. Lefrandt, Nynke Zwart, H. Marike Boezen, Andries J. Smit, Coby Meijer, Jourik A. Gietema^*

^*Corresponding author voor dit werk

Onderzoeksoutput: Article › Academic › peer review

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Purpose: Chemotherapy-treated testicular cancer survivors are at risk for development of the metabolic syndrome, especially in case of decreased androgen levels. Polymorphisms in the gene encoding steroid 5-alpha-reductase type II (SRD5A2) are involved in altered androgen metabolism. We investigated whether single-nucleotide polymorphisms (SNPs) rs523349 (V89L) and rs9282858 (A49T) in SRD5A2 are associated with cardiometabolic status in testicular cancer survivors.

Methods: In 173 chemotherapy-treated testicular cancer survivors, hormone levels and cardiometabolic status were evaluated cross-sectionally (median 5 years [range 3-20] after chemotherapy) and correlated with SNPs in SRD5A2.

Results: The metabolic syndrome was more prevalent in survivors who were homozygous or heterozygous variant for SRD5A2 rs523349 compared to wild type (33% versus 19%, P = 0.032). In particular, patients with lower testosterone levels (

Conclusion: Metabolic syndrome develops more frequently in testicular cancer survivors homozygous or heterozygous variant for SNP rs523349 in SRD5A2. Altered androgen sensitivity appears to be involved in the development of adverse metabolic and vascular changes in testicular cancer survivors and is a target for intervention. (C) 2015 Elsevier Ltd. All rights reserved.

Originele taal-2	English
Pagina's (van-tot)	104-111
Aantal pagina's	8
Tijdschrift	European Journal of Cancer
Volume	54
DOI's	https://doi.org/10.1016/j.ejca.2015.11.009
Status	Published - feb.-2016

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Boer, H., Westerink, N.-D. L., Altena, R., Nuver, J., Dijck-Brouwer, D. A. J., van Faassen, M., Klont, F., Kema, I. P., Lefrandt, J. D., Zwart, N., Boezen, H. M., Smit, A. J., Meijer, C., & Gietema, J. A. (2016). Single-nucleotide polymorphism in the 5-alpha-reductase gene (SRD5A2) is associated with increased prevalence of metabolic syndrome in chemotherapy-treated testicular cancer survivors. European Journal of Cancer, 54, 104-111. https://doi.org/10.1016/j.ejca.2015.11.009

@article{46215e350ff74de7baf9ea79f6cbee18,

title = "Single-nucleotide polymorphism in the 5-alpha-reductase gene (SRD5A2) is associated with increased prevalence of metabolic syndrome in chemotherapy-treated testicular cancer survivors",

abstract = "Purpose: Chemotherapy-treated testicular cancer survivors are at risk for development of the metabolic syndrome, especially in case of decreased androgen levels. Polymorphisms in the gene encoding steroid 5-alpha-reductase type II (SRD5A2) are involved in altered androgen metabolism. We investigated whether single-nucleotide polymorphisms (SNPs) rs523349 (V89L) and rs9282858 (A49T) in SRD5A2 are associated with cardiometabolic status in testicular cancer survivors.Methods: In 173 chemotherapy-treated testicular cancer survivors, hormone levels and cardiometabolic status were evaluated cross-sectionally (median 5 years [range 3-20] after chemotherapy) and correlated with SNPs in SRD5A2.Results: The metabolic syndrome was more prevalent in survivors who were homozygous or heterozygous variant for SRD5A2 rs523349 compared to wild type (33% versus 19%, P = 0.032). In particular, patients with lower testosterone levels (Conclusion: Metabolic syndrome develops more frequently in testicular cancer survivors homozygous or heterozygous variant for SNP rs523349 in SRD5A2. Altered androgen sensitivity appears to be involved in the development of adverse metabolic and vascular changes in testicular cancer survivors and is a target for intervention. (C) 2015 Elsevier Ltd. All rights reserved.",

keywords = "Testicular neoplasms, Survivors, Antineoplastic agents, Testosterone, 3-Oxo-5-alpha-steroid 4-dehydrogenase, Single-nucleotide polymorphism, Metabolic syndrome X, Carotid intima-media thickness, Albuminuria, LONG-TERM SURVIVORS, CARDIOVASCULAR-DISEASE, SERUM TESTOSTERONE, GONADAL-HORMONES, 5-YEAR SURVIVORS, STEROID PROFILE, RISK, MEN, DIAGNOSIS, ANDROGEN",

author = "Hink Boer and Westerink, {Nico-Derk L.} and Renske Altena and Janine Nuver and Dijck-Brouwer, {D. A. Janneke} and {van Faassen}, Martijn and Frank Klont and Kema, {Ido P.} and Lefrandt, {Joop D.} and Nynke Zwart and Boezen, {H. Marike} and Smit, {Andries J.} and Coby Meijer and Gietema, {Jourik A.}",

year = "2016",

month = feb,

doi = "10.1016/j.ejca.2015.11.009",

language = "English",

volume = "54",

pages = "104--111",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "ELSEVIER SCI LTD",

}

Boer, H, Westerink, N-DL, Altena, R, Nuver, J , Dijck-Brouwer, DAJ , van Faassen, M , Klont, F , Kema, IP , Lefrandt, JD , Zwart, N, Boezen, HM, Smit, AJ , Meijer, C & Gietema, JA 2016, 'Single-nucleotide polymorphism in the 5-alpha-reductase gene (SRD5A2) is associated with increased prevalence of metabolic syndrome in chemotherapy-treated testicular cancer survivors', European Journal of Cancer, vol. 54, blz. 104-111. https://doi.org/10.1016/j.ejca.2015.11.009

TY - JOUR

T1 - Single-nucleotide polymorphism in the 5-alpha-reductase gene (SRD5A2) is associated with increased prevalence of metabolic syndrome in chemotherapy-treated testicular cancer survivors

AU - Boer, Hink

AU - Westerink, Nico-Derk L.

AU - Altena, Renske

AU - Nuver, Janine

AU - Dijck-Brouwer, D. A. Janneke

AU - van Faassen, Martijn

AU - Klont, Frank

AU - Kema, Ido P.

AU - Lefrandt, Joop D.

AU - Zwart, Nynke

AU - Boezen, H. Marike

AU - Smit, Andries J.

AU - Meijer, Coby

AU - Gietema, Jourik A.

PY - 2016/2

Y1 - 2016/2

N2 - Purpose: Chemotherapy-treated testicular cancer survivors are at risk for development of the metabolic syndrome, especially in case of decreased androgen levels. Polymorphisms in the gene encoding steroid 5-alpha-reductase type II (SRD5A2) are involved in altered androgen metabolism. We investigated whether single-nucleotide polymorphisms (SNPs) rs523349 (V89L) and rs9282858 (A49T) in SRD5A2 are associated with cardiometabolic status in testicular cancer survivors.Methods: In 173 chemotherapy-treated testicular cancer survivors, hormone levels and cardiometabolic status were evaluated cross-sectionally (median 5 years [range 3-20] after chemotherapy) and correlated with SNPs in SRD5A2.Results: The metabolic syndrome was more prevalent in survivors who were homozygous or heterozygous variant for SRD5A2 rs523349 compared to wild type (33% versus 19%, P = 0.032). In particular, patients with lower testosterone levels (Conclusion: Metabolic syndrome develops more frequently in testicular cancer survivors homozygous or heterozygous variant for SNP rs523349 in SRD5A2. Altered androgen sensitivity appears to be involved in the development of adverse metabolic and vascular changes in testicular cancer survivors and is a target for intervention. (C) 2015 Elsevier Ltd. All rights reserved.

AB - Purpose: Chemotherapy-treated testicular cancer survivors are at risk for development of the metabolic syndrome, especially in case of decreased androgen levels. Polymorphisms in the gene encoding steroid 5-alpha-reductase type II (SRD5A2) are involved in altered androgen metabolism. We investigated whether single-nucleotide polymorphisms (SNPs) rs523349 (V89L) and rs9282858 (A49T) in SRD5A2 are associated with cardiometabolic status in testicular cancer survivors.Methods: In 173 chemotherapy-treated testicular cancer survivors, hormone levels and cardiometabolic status were evaluated cross-sectionally (median 5 years [range 3-20] after chemotherapy) and correlated with SNPs in SRD5A2.Results: The metabolic syndrome was more prevalent in survivors who were homozygous or heterozygous variant for SRD5A2 rs523349 compared to wild type (33% versus 19%, P = 0.032). In particular, patients with lower testosterone levels (Conclusion: Metabolic syndrome develops more frequently in testicular cancer survivors homozygous or heterozygous variant for SNP rs523349 in SRD5A2. Altered androgen sensitivity appears to be involved in the development of adverse metabolic and vascular changes in testicular cancer survivors and is a target for intervention. (C) 2015 Elsevier Ltd. All rights reserved.

KW - Testicular neoplasms

KW - Survivors

KW - Antineoplastic agents

KW - Testosterone

KW - 3-Oxo-5-alpha-steroid 4-dehydrogenase

KW - Single-nucleotide polymorphism

KW - Metabolic syndrome X

KW - Carotid intima-media thickness

KW - Albuminuria

KW - LONG-TERM SURVIVORS

KW - CARDIOVASCULAR-DISEASE

KW - SERUM TESTOSTERONE

KW - GONADAL-HORMONES

KW - 5-YEAR SURVIVORS

KW - STEROID PROFILE

KW - RISK

KW - MEN

KW - DIAGNOSIS

KW - ANDROGEN

U2 - 10.1016/j.ejca.2015.11.009

DO - 10.1016/j.ejca.2015.11.009

M3 - Article

SN - 0959-8049

VL - 54

SP - 104

EP - 111

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -

Single-nucleotide polymorphism in the 5-alpha-reductase gene (SRD5A2) is associated with increased prevalence of metabolic syndrome in chemotherapy-treated testicular cancer survivors

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