title: [Polymorphisms of KITLG, SPRY4, and BAK1 genes in patients with testicular germ cell tumors and individuals with infertility associated with AZFc deletion of the Y chromosome].
abstract: Testicular cancer is the most common form of solid cancer in young men. Testicular cancer is represented by testicular germ cell tumors (TGCTs) derived from embryonic stem cells with different degrees of differentiation in about 95% of cases. The development of these tumors is related to the formation of a pool of male germ cells and gametogenesis. Clinical factors that are predisposed to the development of germ-cell tumors include cryptorchidism and testicular microlithiasis, as well as infertility associated with the gr/gr deletion within the AZFс locus. KITLG, SPRY4, and BAK1 genes affect the development of the testes and gametogenesis; mutations and polymorphisms of these genes lead to a significant increase in the risk of the TGCT development. To determine the relationship between gene polymorphisms and the development of TGCTs, we developed a system for detection and studied the allele and genotype frequencies of the KITLG (rs995030, rs1508595), SPRY4 (rs4624820, rs6897876), and BAK1 (rs210138) genes in fertile men, patients with TGCTs, and patients with infertility that have the AZFс deletion. A significant association of rs995030 of the KITLG gene with the development of TGCTs (p = 0.029 for the allele G, p = 0.0124 for the genotype GG) was revealed. Significant differences in the frequencies of the studied polymorphisms in patients with the AZFc deletion and the control group of fertile men were not found. We showed significant differences in the frequencies for the combination of all high-risk polymorphisms in the control group, patients with the AZFc deletion and patients with TGCTs (p (TGCTs-AZF-control) = 0.0207). A fivefold increase in the frequency of the combination of all genotypes in the TGCT group (p = 0.0116; OR = 5.25 [1.44-19.15]) and 3.7-fold increase was identified in patients with the AZFc deletion (p = 0.045; OR = 3.69 [1.11-12.29]) were revealed. The genotyping of patients with infertility caused by the AZFc deletion can be used to identify individuals with an increased risk of TGCTs.
authors.affiliation: Russian Medical Academy of Postgraduate Education, Moscow, 123995 Russia.|Medical Genetic Scientific Centre, Moscow, 115478 Russia.|nemtsova_m_v@mail.ru.
authors.forename: M V
authors.initials: MV
authors.lastname: Nemtsova
authors.affiliation: Russian Medical Academy of Postgraduate Education, Moscow, 123995 Russia.
authors.forename: E V
authors.initials: EV
authors.lastname: Ivkin
authors.affiliation: Medical Genetic Scientific Centre, Moscow, 115478 Russia.
authors.forename: O A
authors.initials: OA
authors.lastname: Simonova
authors.affiliation: Medical Genetic Scientific Centre, Moscow, 115478 Russia.
authors.forename: V V
authors.initials: VV
authors.lastname: Rudenko
authors.affiliation: Medical Genetic Scientific Centre, Moscow, 115478 Russia.
authors.forename: V B
authors.initials: VB
authors.lastname: Chernykh
authors.affiliation: Lopatkin Scientific Research Institute of Urology and Interventional Radiology, 105425 Russia.
authors.forename: D S
authors.initials: DS
authors.lastname: Mikhaylenko
authors.affiliation: Russian Medical Academy of Postgraduate Education, Moscow, 123995 Russia.
authors.forename: O B
authors.initials: OB
authors.lastname: Loran
mesh_terms: D000328:Adult; D001483:Base Sequence; D041322:Chromosomes, Human, Y / Q000235:genetics*; D056426:Genetic Loci; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017384:Sequence Deletion; D019089:Stem Cell Factor / Q000235:genetics*; D013736:Testicular Neoplasms / Q000235:genetics*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics*
chemical_list: C494772:BAK1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C499038:SPRY4 protein, human; D019089:Stem Cell Factor; D050998:bcl-2 Homologous Antagonist-Killer Protein
keywords: high-risk genotype; risk factor; single nucleotide polymorphism; testicular germ cell tumor (TGCT)