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The polymorphic hMSH 5 C85T allele augments radiotherapy‐induced spermatogenic impairment
Author(s) -
Zhu Y.,
Gao G.,
Xia L.,
Li X.,
Wu X.,
Her C.,
Xu K.
Publication year - 2016
Publication title -
andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 43
eISSN - 2047-2927
pISSN - 2047-2919
DOI - 10.1111/andr.12203
Subject(s) - radiation therapy , genotype , dna fragmentation , dna damage , biology , sperm , allele , dna repair , male infertility , semen , cancer research , infertility , germ cell , andrology , genetics , oncology , apoptosis , dna , medicine , programmed cell death , gene , pregnancy
Summary The hMSH 5 C85T polymorphism (encoding hMSH 5 P29S) is associated with male infertility and radiation‐induced apoptotic response. To date, however, the potential association of hMSH 5 C85T polymorphism with DNA damage accumulation in spermatozoa of cancer patients treated with radiotherapy is largely unknown. We investigated hMSH 5 C85T allele and genotype frequencies, routine semen analysis and sperm DNA Fragmentation Index ( DFI ) in 113 testicular germ cell tumor ( TGCT ) patients before and after radiotherapy. The hMSH 5 C85T allele is not associated with the occurrence of TGCT . However, in comparison with the CC genotype, TGCT patients with the CT + TT genotypes showed significantly altered sperm counts, sperm morphology and DFI after radiotherapy. Finally, the results of the DSB repair assay demonstrated that hMSH 5 P29S could enhance radiotherapy‐induced DNA damage by unleashing error‐prone non‐homologous end joining. Together, our studies indicate that the hMSH 5 C85T variation could have an impact on the severity of radiotherapy‐provoked long‐term side effects through compromising the repair of radiation‐induced DNA lesions.