Elzinga-Tinke Jenny E, Dohle Gert R, Looijenga Leendert Hj
Department of Pathology, Laboratory of Experimental Patho-Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, Netherlands.
Asian J Androl. 2015 May-Jun;17(3):381-93. doi: 10.4103/1008-682X.148079.
Malignant testicular germ cell tumors (TGCT) are the most frequent cancers in Caucasian males (20-40 years) with an 70% increasing incidence the last 20 years, probably due to combined action of (epi)genetic and (micro)environmental factors. It is expected that TGCT have carcinoma in situ(CIS) as their common precursor, originating from an embryonic germ cell blocked in its maturation process. The overall cure rate of TGCT is more than 90%, however, men surviving TGCT can present long-term side effects of systemic cancer treatment. In contrast, men diagnosed and treated for CIS only continue to live without these long-term side effects. Therefore, early detection of CIS has great health benefits, which will require an informative screening method. This review described the etiology and early pathogenesis of TGCT, as well as the possibilities of early detection and future potential of screening men at risk for TGCT. For screening, a well-defined risk profile based on both genetic and environmental risk factors is needed. Since 2009, several genome wide association studies (GWAS) have been published, reporting on single-nucleotide polymorphisms (SNPs) with significant associations in or near the genes KITLG, SPRY4, BAK1, DMRT1, TERT, ATF7IP, HPGDS, MAD1L1, RFWD3, TEX14, and PPM1E, likely to be related to TGCT development. Prenatal, perinatal, and postnatal environmental factors also influence the onset of CIS. A noninvasive early detection method for CIS would be highly beneficial in a clinical setting, for which specific miRNA detection in semen seems to be very promising. Further research is needed to develop a well-defined TGCT risk profile, based on gene-environment interactions, combined with noninvasive detection method for CIS.
恶性睾丸生殖细胞肿瘤（TGCT）是白种男性（20 - 40岁）中最常见的癌症，在过去20年中发病率增加了70%，这可能是遗传和（微）环境因素共同作用的结果。预计TGCT以原位癌（CIS）为常见前驱病变，起源于成熟过程受阻的胚胎生殖细胞。TGCT的总体治愈率超过90%，然而，TGCT幸存者可能会出现全身癌症治疗的长期副作用。相比之下，仅被诊断和治疗CIS的男性继续生活而无这些长期副作用。因此，早期发现CIS具有巨大的健康益处，这将需要一种信息丰富的筛查方法。本综述描述了TGCT的病因和早期发病机制，以及TGCT高危男性早期检测和未来筛查潜力的可能性。对于筛查，需要基于遗传和环境风险因素的明确风险概况。自2009年以来，已经发表了几项全基因组关联研究（GWAS），报告了与KITLG、SPRY4、BAK1、DMRT1、TERT、ATF7IP、HPGDS、MAD1L1、RFWD3、TEX14和PPM1E基因内或附近有显著关联的单核苷酸多态性（SNP），这些基因可能与TGCT的发生有关。产前、围产期和产后环境因素也会影响CIS的发病。一种用于CIS的非侵入性早期检测方法在临床环境中将非常有益，精液中特定miRNA的检测似乎非常有前景。需要进一步研究以基于基因 - 环境相互作用以及CIS的非侵入性检测方法来制定明确的TGCT风险概况。
