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Estrogen receptor alpha single nucleotide polymorphism modifies the risk of azoospermia in childhood cancer survivors

Romerius, Patrik LU ; Giwercman, Aleksander LU ; Moëll, Christian LU ; Relander, Thomas LU ; Cavallin-Ståhl, Eva LU ; Wiebe, Thomas LU ; Halldén, Christer LU and Giwercman, Yvonne LU (2011) In Pharmacogenetics & Genomics 21(5). p.263-269
Abstract
OBJECTIVE: Cancer treatment in childhood leads to permanent azoospermia in a significant number of boys and those who are diagnosed with cancer before puberty do not have the option of pretreatment cryopreservation of spermatozoa. However, there is an interindividual variation in the sensitivity to gonadotoxic effects of cancer therapy, which probably is due to genetic factors. Identification of genetic markers for the risk of azoospermia in childhood cancer survivors may help in identifying boys to whom testicular cryopreservation should be offered. METHODS: Fifty-one single nucleotide polymorphisms (SNPs) being markers of 12 different haplotype blocks in the androgen receptor, estrogen receptor (ER) α and ER β genes were examined in 127... (More)
OBJECTIVE: Cancer treatment in childhood leads to permanent azoospermia in a significant number of boys and those who are diagnosed with cancer before puberty do not have the option of pretreatment cryopreservation of spermatozoa. However, there is an interindividual variation in the sensitivity to gonadotoxic effects of cancer therapy, which probably is due to genetic factors. Identification of genetic markers for the risk of azoospermia in childhood cancer survivors may help in identifying boys to whom testicular cryopreservation should be offered. METHODS: Fifty-one single nucleotide polymorphisms (SNPs) being markers of 12 different haplotype blocks in the androgen receptor, estrogen receptor (ER) α and ER β genes were examined in 127 adult childhood cancer survivors. RESULTS: In ERα, markers of one specific haplotype block (rs2207396, rs9340958, rs9340978) were associated with an increased risk of azoospermia. Compared with those with the GG genotype, patients being heterozygous for the A allele in rs2207396 had a significantly increased risk of azoospermia [odds ratio (OR): 3.8; 95% confidence interval: 1.5-9.5; P=0.008], this OR being even higher in the subgroup treated with alkylating drugs (OR: 8.8; 95% confidence interval: 2.1-36; P=0.004). In this subgroup, 48% of the patients carried the A allele of rs2207396, this proportion being 70% among the azoospermic patients. CONCLUSION: Use of genetic markers of high risk of posttreatment azoospermia may, in the future, prove an important clinical tool in selection of boys to whom preservation of testicular tissue before cancer therapy should be offered. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
azoospermia, childhood cancer survivors, estrogen receptor a, polymorphism
in
Pharmacogenetics & Genomics
volume
21
issue
5
pages
263 - 269
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000289460200003
  • scopus:79955467679
  • pmid:21430602
ISSN
1744-6872
DOI
10.1097/FPC.0b013e328343a132
language
English
LU publication?
yes
id
9d5d64b0-3d5a-4690-9f71-a4df111b2050 (old id 1965294)
date added to LUP
2011-06-01 10:47:47
date last changed
2017-09-03 03:30:29
@article{9d5d64b0-3d5a-4690-9f71-a4df111b2050,
  abstract     = {OBJECTIVE: Cancer treatment in childhood leads to permanent azoospermia in a significant number of boys and those who are diagnosed with cancer before puberty do not have the option of pretreatment cryopreservation of spermatozoa. However, there is an interindividual variation in the sensitivity to gonadotoxic effects of cancer therapy, which probably is due to genetic factors. Identification of genetic markers for the risk of azoospermia in childhood cancer survivors may help in identifying boys to whom testicular cryopreservation should be offered. METHODS: Fifty-one single nucleotide polymorphisms (SNPs) being markers of 12 different haplotype blocks in the androgen receptor, estrogen receptor (ER) α and ER β genes were examined in 127 adult childhood cancer survivors. RESULTS: In ERα, markers of one specific haplotype block (rs2207396, rs9340958, rs9340978) were associated with an increased risk of azoospermia. Compared with those with the GG genotype, patients being heterozygous for the A allele in rs2207396 had a significantly increased risk of azoospermia [odds ratio (OR): 3.8; 95% confidence interval: 1.5-9.5; P=0.008], this OR being even higher in the subgroup treated with alkylating drugs (OR: 8.8; 95% confidence interval: 2.1-36; P=0.004). In this subgroup, 48% of the patients carried the A allele of rs2207396, this proportion being 70% among the azoospermic patients. CONCLUSION: Use of genetic markers of high risk of posttreatment azoospermia may, in the future, prove an important clinical tool in selection of boys to whom preservation of testicular tissue before cancer therapy should be offered.},
  author       = {Romerius, Patrik and Giwercman, Aleksander and Moëll, Christian and Relander, Thomas and Cavallin-Ståhl, Eva and Wiebe, Thomas and Halldén, Christer and Giwercman, Yvonne},
  issn         = {1744-6872},
  keyword      = {azoospermia,childhood cancer survivors,estrogen receptor a,polymorphism},
  language     = {eng},
  number       = {5},
  pages        = {263--269},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Pharmacogenetics & Genomics},
  title        = {Estrogen receptor alpha single nucleotide polymorphism modifies the risk of azoospermia in childhood cancer survivors},
  url          = {http://dx.doi.org/10.1097/FPC.0b013e328343a132},
  volume       = {21},
  year         = {2011},
}