Testicular germ cell tumors (TGCTs), the most common neoplasms of young men, are categorized histologically as either seminomas or nonseminomas/mixed germ cell tumors. These subtypes differ by age at diagnosis and clinical course, but little is known about etiological distinctions. To test the hypothesis that histological subtypes have distinct sets of unrecognized etiological factors, we used a recently described approach, estimating the association between histological types of first and second tumors of men with 2 primary TGCTs. The study population of 488 men each with 2 primary TGCTs was ascertained through population-based cancer registries in the United States between 1972 and 2006. Univariate logistic regression analysis revealed that the histology of second primary TGCTs was associated with the histology of first TGCTs (odds ratio = 1.70, 95% confidence interval: 1.14, 2.52); however, the association did not persist in analyses adjusted for age at diagnosis of first TGCT (odds ratio = 1.09, 95% confidence interval: 0.71, 1.70). These results would be expected if the subtypes share etiology but experience different rates of progression to diagnosis or if the histological fate of TGCTs is influenced by age-related processes. Men with 2 primary TGCTs provide novel opportunities to learn whether histological subtypes are likely to share etiology, so results may inform research designed to identify causes.
Keywords: causality; germ cell neoplasms; metachronous second primary neoplasms; multiple primary neoplasms; second primary neoplasms; seminoma; synchronous multiple primary neoplasms; testicular neoplasms.