Nemtsova M V, Ivkin E V, Simonova O A, Rudenko V V, Chernykh V B, Mikhaylenko D S, Loran O B
Russian Medical Academy of Postgraduate Education, Moscow, 123995 Russia.
Medical Genetic Scientific Centre, Moscow, 115478 Russia.
Mol Biol (Mosk). 2016 Nov-Dec;50(6):960-967. doi: 10.7868/S002689841605013X.
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.
睾丸癌是年轻男性中最常见的实体癌形式。在约95%的病例中，睾丸癌由源自胚胎干细胞且具有不同分化程度的睾丸生殖细胞肿瘤（TGCTs）代表。这些肿瘤的发生与男性生殖细胞池的形成和配子发生有关。易患生殖细胞肿瘤的临床因素包括隐睾症和睾丸微石症，以及与AZFс基因座内gr/gr缺失相关的不育症。KITLG、SPRY4和BAK1基因影响睾丸的发育和配子发生；这些基因的突变和多态性会导致TGCT发生风险显著增加。为了确定基因多态性与TGCTs发生之间的关系，我们开发了一种检测系统，并研究了KITLG（rs995030、rs1508595）、SPRY4（rs4624820、rs6897876）和BAK1（rs210138）基因在可育男性、TGCT患者以及具有AZFс缺失的不育患者中的等位基因和基因型频率。发现KITLG基因的rs995030与TGCTs的发生存在显著关联（等位基因G的p = 0.029，基因型GG的p = 0.0124）。未发现AZFc缺失患者与可育男性对照组在研究的多态性频率上存在显著差异。我们发现对照组、AZFc缺失患者和TGCT患者中所有高风险多态性组合的频率存在显著差异（p（TGCTs - AZF - 对照）= 0.0207）。在TGCT组中，所有基因型组合的频率增加了五倍（p = 0.0116；OR = 5.25 [1.44 - 19.15]），在AZFc缺失患者中增加了3.7倍（p = 0.045；OR = 3.69 [1.11 - 12.29]）。对由AZFc缺失导致不育的患者进行基因分型可用于识别TGCTs风险增加的个体。
