Risk of testicular germ cell tumors and polymorphisms in the insulin-like growth factor genes

Because taller men are at increased risk of developing testicular germ cell tumors (TGCT), it is conceivable that factors that influence adult height could be related to risk of TGCT. Because common genetic variation in genes of the insulin-like growth factor (IGF) pathway could influence somatic growth, 43 single nucleotide polymorphisms in four IGF genes (IGF-1, IGF-1R, IGF-2, and IGFALS) were genotyped in 577 case and 707 control participants from the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study to assess relationships with TGCT risk; additionally, associations between polymorphisms and adult height were examined. Relationships between polymorphisms and adult height were assessed using adjusted linear regression models, and associations between polymorphisms and TGCT risk were determined by adjusted logistic regression models estimating odds ratios. Although four IGF-1R polymorphisms (rs907806, rs3743258, rs229765, and rs9282714) were associated with height (P_trend < 0.05), there were no relationships with any other polymorphism. Overall, there were no associations among polymorphisms or haplotypes in the IGF genes and TGCT risk, with odds ratios ranging from 0.55 to 1.50. Similarly, there was no association among the polymorphisms and risk of specific TGCT histologies (seminoma and nonseminoma). There was a suggestion, however, that adult height may modify the relationship between an IGF-1 haplotype and TGCT risk. These results suggest that, in aggregate, genetic variation in IGF loci is not associated with TGCT risk.