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  • Germ cell tumors are the most common histologic subtype

    2019-08-16

    Germ cell tumors are the most common histologic subtype of testicular cancer in all age groups [37] and the majority of etiologic studies of testicular cancer have focused on GCT. In the AYA group, 98% of testicular cancers arise in the germ cells, so the results of TGCT studies would apply to the vast majority of testicular cancers. In contrast, in the pediatric age group, a larger percentage of tumors are of non-germinal origin so results from studies of TGCT may not be representative of all testicular cancers in this age group. We did observe similar patterns in incidence rates when we restricted the analysis to testicular cancer of germ cell histology. Several lines of evidence exist to suggest etiologic differences in GCTs occurring in children and young adults, with adolescents having disease which more closely resembles adults [38,39]. This may explain some of the difference in geographic incidence patterns for testicular cancer by age group. The profile of chromosomal alterations is the most notable difference between pediatric and AYA GCTs, with studies suggesting that age is a stronger predictor of chromosomal abnormalities than tumor histology. [40] Adults and adolescents have aneuploid tumors with gain of 12p [38] most commonly due to isochromosome 12p formation [41]. In contrast, gain of 12p is rarely observed in pediatric GCT while recurrent alterations are seen on Temozolomide 1, 3, and Temozolomide 6 [42,43]. The well-documented increase in TGCT in adolescents and young adults [9,44] also does not appear to be occurring in young boys [4,19,21,45,46], providing further evidence in support of differing etiologies. However, despite these differences, there are some shared etiologic risk factors for testicular GCTs occurring in children and AYA, including an increased risk associated with cryptorchidism [34] and shared genetic susceptibility variants [47]. Several lines of evidence support in utero origins of adult testicular cancer [38,48,49]. Similarly, many childhood cancers are thought to originate in utero [50]. For this reason, in utero exposures and perinatal variables have been evaluated as risk factors for AYA and pediatric testicular cancer. In young adults, results from a meta-analysis of maternal variables support associations of maternal bleeding during pregnancy, birth order, sibship size and possibly caesarean section with risk of testicular cancer in sons [32]. A separate meta-analysis evaluating variables in the testicular cancer cases found evidence that cryptorchidism, inguinal hernia and twinning are associated with risk of testicular cancer [31]. This study also reported suggestive evidence for an association with birth weight and gestational age [31]. Endocrine disruptors have also been evaluated as risk factors, with evidence that persistent organochlorine pesticides may be associated with risk [51]. In the pediatric age group, studies including testicular cancers of all histologic subtypes have not been conducted; however, perinatal variables and in utero exposures have been evaluated as risk factors for germ cell tumors [52]. With the exception of higher birth weight being associated with increased risk of GCT [53,54], none of the birth characteristics evaluated to date has emerged as a potential risk factor for pediatric GCT overall. Findings for studies of in utero exposures have also been mixed, with the majority of studies being underpowered to detect associations [52]. Differing prevalence of in utero exposures and perinatal factors could explain the differences in incidence rates by geographic location. For example, considerable global variation exists for birth weight [55,56] and rates of caesarean section [57]; however, since these variables have not been established conclusively as risk factors for testicular cancer across the age spectrum it would be premature to evaluate correlations between the prevalence of these factors and testicular cancer incidence.