Genes associated with testicular germ cell tumors and testicular dysgenesis in patients with testicular microlithiasis

Abstract

Testicular microlithiasis (TM) is one of the symptoms of testicular dysgenesis syndrome (TDS). TM is particularly interesting as an informative marker of testicular germ cell tumors (TGCTs). KIT ligand gene (KITLG), BCL2 antagonist/killer 1 (BAK1), and sprouty RTK signaling antagonist 4 (SPRY4) genes are associated with a high risk of TGCTs, whereas bone morphogenetic protein 7 gene (BMP7), transforming growth factor beta receptor 3 gene (TGFBR3), and homeobox D cluster genes (HOXD) are related to TDS. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, we investigated allele and genotype frequencies for KITLG (rs995030, rs1508595), SPRY4 (rs4624820, rs6897876), BAK1 (rs210138), BMP7 (rs388286), TGFBR3 (rs12082710), and HOXD (rs17198432) in 142 TGCT patients, 137 TM patients, and 153 fertile men (control group). We found significant differences in the KITLG GG_rs995030 genotype in TM (P = 0.01) and TGCT patients (P = 0.0005) compared with the control. We also revealed strong associations between KITLG_rs1508595 and TM (G allele, P = 0.003; GG genotype, P = 0.01) and between KITLG_rs1508595 and TGCTs (G allele, P = 0.0001; GG genotype, P = 0.0007). Moreover, there was a significant difference in BMP7_rs388286 between the TGCT group and the control (T allele, P = 0.00004; TT genotype, P = 0.00006) and between the TM group and the control (T allele, P = 0.04). HOXD also demonstrated a strong association with TGCTs (rs17198432 A allele, P = 0.0001; AA genotype, P = 0.001). Furthermore, significant differences were found between the TGCT group and the control in the BAK1_rs210138 G allele (P = 0.03) and the GG genotype (P = 0.01). KITLG and BMP7 genes, associated with the development of TGCTs, may also be related to TM. In summary, the KITLG GG_rs995030, GG_rs1508595, BMP7 TT_rs388286, HOXD AA_rs17198432, and BAK1 GG_rs210138 genotypes were associated with a high risk of TGCT development.

Effects of testicular dysgenesis syndrome components on testicular germ cell tumor prognosis and oncological outcomes

“…From this point of view, we can think that embryological development and pathogenesis of all these disorders mentioned above is caused by a common fetal origin. This condition can be interpreted as supporting the TDS hypothesis ( 20 ).…”

Hypogonadism and Sexual Dysfunction in Testicular Tumor Survivors: A Systematic Review

“…The reason why mycrolithiasis may somehow be associated with a higher risk of Leydig cell failure might be inherent to the possible existence of a tumor-dependent mechanism of Leydig cell damage. Testicular mycrolithiasis belongs to the TDS spectrum, the latter syndrome being considered to be involved in testicular tumor pathogenesis (26, 27).…”

HOXD3 was negatively regulated by YY1 recruiting HDAC1 to suppress progression of hepatocellular carcinoma cells via ITGA2 pathway

“…26 In the previous study, HOX genes are found in the development of various cancers, such as head and neck cancer acute myeloid leukaemia, 27 ovarian cancer 28 and bladder cancer. 29 The dysregulated expression of HOXD, as a member of HOX family, has been identified in solid tumours, including testicular germ cell tumours, 30 ewing sarcoma 31 and breast cancer. 32 The research of ewing sarcoma exhibited that HOXD11 and HOXD13 promoted growth and metastasis of ewing sarcoma.…”