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Estrogen receptor α single nucleotide polymorphism modifies the risk of azoospermia in childhood cancer survivors
Department of Pediatrics, Skåne University Hospital, Lund.
Department of Laboratory Medicine, Skåne University Hospital, Lund.
Department of Pediatrics, Skåne University Hospital, Lund.
Department of Oncology, Skåne University Hospital, Lund.
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2011 (English)In: Pharmacogenetics & Genomics, ISSN 1744-6872, Vol. 21, no 5, 263-269 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2011. Vol. 21, no 5, 263-269 p.
Keyword [en]
azoospermia, childhood cancer survivors, estrogen receptor alpha polymorphism
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:hkr:diva-8157DOI: 10.1097/FPC.0b013e328343a132ISI: 000289460200003PubMedID: 21430602OAI: oai:DiVA.org:hkr-8157DiVA: diva2:424414
Available from: 2011-06-17 Created: 2011-06-17 Last updated: 2014-06-10Bibliographically approved

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