Abstract 4468: Pre-diagnostic steroid hormone levels and risk of testicular germ cell tumors

Abstract

Abstract Background: Testicular germ cell tumors (TGCT), the most commonly occurring cancer among young men in the U.S., are thought to be endocrine-related tumors. The relationship between steroid hormone levels and development of TGCT, however, has been difficult to study given the rarity of the tumor in the general population and the paucity of pre-diagnostic serum from young men. The U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study, however, was able to overcome these obstacles by enrolling military servicemen who had previously donated serum specimens to the Department of Defense Serum Repository. Methods: STEED participants were enrolled between 2002 and 2005. The associations between TGCT risk and log-transformed serum concentrations of testosterone, free testosterone, estradiol, free estradiol, 3α-androstanediol glucuronide (3α-diol-G), an indicator of peripheral androgen action, and sex hormone-binding globulin (SHBG) were examined in 517 case and 790 control participants. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models, adjusting for date of serum donation, age, race/ethnicity, family history of testicular cancer, history of cryptorchidism, height, and body mass index. Results: The analysis found that while testosterone was not significantly associated with TGCT risk, there was an inverse association between 3α-diol-G and risk (OR=0.80, 95%CI=0.63-0.99). In addition, there was a significant inverse association with TGCT and the ratio of 3α-diol-G to testosterone (OR=0.76, 95%CI=0.61-0.93). There was also a significant direct association between estradiol and TGCT risk (OR=1.41, 95%CI=1.06-1.87). The relationships between the free forms of testosterone and estradiol and risk were the same as the relationships between the total forms of each hormone and risk. There was no association between TGCT and SHBG. Conclusion: These results suggest that the hormone metabolism of men who subsequently develop TGCT may vary from that of other men. In men who develop TGCT, more testosterone may be converted to estradiol and less to dihydrotestosterone, the most potent form of androgen, than in men who do not develop TGCT. Further examination of metabolites, both upstream and downstream in the steroid hormone pathway, may help elucidate the mechanism by which these exposures are related to development of TGCT. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4468. doi:1538-7445.AM2012-4468