Abstract 4470: Pre-diagnostic gonadotropin levels and development of testicular germ cell tumors

Abstract

Abstract INTRODUCTION: Testicular germ cell tumors (TGCT) are the most common cancer among young men (20-45 years of age). The pathogenesis of TGCT remains largely unknown; however, there is evidence that TGCT is related to other male reproductive disorders namely infertility and genitourinary malformations (cryptorchidism and hypospadias). It is generally assumed that the development of TGCT is under endocrine control and it has been hypothesized that gonadotropin dysregulation may be one potential cause of TGCT, as the testes are primary target organs for the gonadotropins, follicle-stimulating hormone (FSH) and luteinzing hormone (LH). FSH stimulates spermatogenesis via binding to receptors in Sertoli cells, while LH stimulates the Leydig cells to produce testosterone. Data support the role of primary LH deficiency in cryptorchidism, and also support the role of gonadotropin deficiency in infertility. It is currently not known whether FSH and LH levels are associated with TGCT risk. Thus, we assessed associations of pre-diagnostic serum FSH and LH concentrations and risk of TGCT among participants in the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) Study. METHODS: TGCT cases diagnosed between 2002 and 2005 (n=517) were matched on age, race and serum draw date to at least one control (n=790). Associations between pre-diagnostic serum FSH and LH levels and TGCT were estimated using conditional logistic regression with further adjustment for prior cryptorchidism, family history of testicular cancer, height, body mass index and serum testosterone. Associations stratified on histology (seminoma, nonseminoma) were also examined. RESULTS: Overall, TGCT was associated with increased levels of FSH and decreased levels of LH. Men had an increased risk of TGCT if they were in the highest quartile of FSH [Q4 vs. Q1: OR 2.17, 95% CI 1.35-3.48] and in the lowest quartile of LH [Q1 vs. Q4: OR 1.99, 95% CI 1.25-3.16]. These associations were independent of one another and independent of serum testosterone concentration. In analyses stratified by histologic subtype the increased risk of TGCT with high FSH [Q4 vs. Q1: OR 2.86, 95% CI 1.33-6.18] and low LH [Q1 vs. Q4: OR 2.55, 95% CI 1.18, 5.49] was consistent for seminomas. Among nonseminomas, the ORs were indicative of elevated TGCT risk with high FSH [Q4 vs. Q1: OR 1.81, 95% CI 0.96-3.43] and low LH [Q1 vs. Q4: OR 1.80, 95% CI 0.97-3.36], albeit the results did not attain statisitical significance. DISCUSSION: Our findings of associations of TGCT with FSH and LH suggest that gonadotropin disruption may be a critical event in development of TGCT. LH deficiency has previously been associated with risk factors for TGCT, cryptorchidism and infertility, while high levels of FSH may indicate a defect in Sertoli cell production of inhibin B, a negative feedback regulator of FSH. 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 4470. doi:1538-7445.AM2012-4470