Insulin-like growth factors and risk of testicular germ cell tumors

B101

Studies have consistently shown that taller height in men is associated with an increased risk of testicular germ cell tumors (TGCT). Thus, it is plausible that factors associated with height, such as the insulin-like growth factor (IGF) pathway, may also influence TGCT risk. Using 577 case and 790 control participants from the U.S. Servicemen’s Testicular Tumor Environmental and Endocrine Determinants (STEED) Study, we assessed associations between 43 single nucleotide polymorphisms in 4 key IGF genes (IGF-1, IGF-1R, IGF-2, and IGFALS) and risk of TGCT. We also examined associations between TGCT risk and serum concentrations of IGF-1 and IGF binding protein-3 (IGFBP-3); in addition serum relationships with height were determined. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using adjusted logistic regression models. No associations between the IGF pathway polymorphisms and risk of TGCT or of specific TGCT histologic types (seminoma and nonseminoma) were observed. Serum IGF-1 concentrations were associated with height; men who had the highest concentrations of IGF-1 were taller than men with lower IGF-1 concentrations (p-trend=0.002). Associations between height and IGFBP-3 concentrations were not as clear, although there was a suggestion that men with higher IGFBP-3 concentrations were taller. There were no associations between IGF-1 or IGFBP-3 concentrations and TGCT risk overall. However, when cases were separated by histology, there was a suggestion of a reduction in seminoma, but not nonseminoma, risk associated with the highest quartile of IGF-1 concentrations compared to the lowest (OR=0.66, 95% CI, 0.40-1.09). No associations by histology were observed with IGFBP-3 concentrations. These results suggest that even though associations between IGF gene polymorphisms and TGCT were not observed, serum IGF-1 concentrations, however, contrary to the hypothesis, may be associated with seminoma risk, but not overall TGCT or nonseminoma risk.