A Case-Control Study of Testicular Germ Cell Tumors Among U.S. Military Servicemen
Condition: Testicular Cancer
MeSH terms: Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms
Study type: Observational

Summary: 
      The incidence of testicular germ cell tumors (TGCT) has increased during the twentieth
      century and is of particular concern as it primarily affects young men. It is the most common
      cancer among U.S. males ages 25-34. The only well-described risk factors are cryptorchism
      (undescended testis), family history of TGCT, and personal history of TGCT. To better
      understand the environmental and genetic determinants of TGCT risk, a case-control study will
      be conducted among members of the U.S. armed forces. The study will include men who have
      donated a blood sample to the Department of Defense Serum Repository (DoDSR) between 1989 and
      2000. All DoDSR donors who have developed GCT will be matched to DoDSR donors who have not
      developed TGCT. Approximately 1,080 men with TGCT, 1,080 controls, and 2,160 mothers will be
      included in the study.

      The DoDSR serum sample will be tested for organochlorines levels, gonadotropin levels, and
      viral antibody titres. Each participant will donate a saliva specimen that will be used in an
      examination of genetic susceptibility. Each participant will also complete a questionnaire
      concerning a variety of possible risk factors such as physical activity, medical history,
      medication history, and other risk factors. The mothers of all participants will be invited
      to participate by completing a questionnaire concerning perinatal exposures and events and by
      donating a saliva sample.

      The three main objectives of this study are to:

        -  determine whether environmental endocrine modulators (i.e., chlorinated pesticides and
           polychlorinated biphenyls) are related to risk of GCT and, if so, whether their effects
           are augmented by other risk factors.

        -  determine whether genetic susceptibility to GCT exists and to characterize the
           environmental risk factors related to that susceptibility.

        -  determine whether there are distinct causes of GCT by relating the tissue structures of
           the tumors to the risk factors.
    

Detailed description: 
      The incidence of testicular germ cell tumors (TGCT) has increased during the better part of
      the twentieth century and is of particular concern as it primarily affects young men. Though
      the tumor is relatively infrequent in the population as a whole, TGCT is the most common
      cancer among U.S. males in the age group 15-34 years. Despite the increases in TGCT rates,
      the etiology is still poorly understood. The only well described risk factors for TGCT are
      cryptorchism, family history of TGCT and personal history of TGCT. Therefore, in order to
      understand better the environmental and genetic determinants of TGCT risk, a case-control
      study will be conducted among members of the U.S. Armed Forces. The study will include men
      who have donated a blood sample to the Department of Defense Serum Repository (DoDSR) between
      the years 1989 and 2003. All DoDSR donors who have developed GCT will be matched to DoDSR
      donors who have not developed TGCT.

      A total of 1682 servicemen were enrolled in the study; 754 cases and 928 controls. Of these
      participants, 1303 men (77%, 590 cases, 713 controls) donated buccal cell samples. In
      addition to the servicemen, a total of 1090 mothers of servicemen were enrolled and 952 (87%)
      provided a buccal specimen. The DoDSR serum samples have been assayed for levels of
      organochlorines pesticides, polychlorinated biphenyl congeners, insulin-like growth factors
      and gonadotropins and steroid hormones. DNA isolated from the buccal cell specimens have thus
      far been genotyped for polymorphysms in the hormone metabolism and immune function pathway,
      immune function pathway, insulin-like growth factor pathway and for single nucleotide
      polymorphisms in the 8q24 locus. In addition, a genome-wide association study has completed.
      Statistical analyses of the questionnaire data are continuing.
    

Observational model: Case-Control
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Male U.S. servicemen, age 18-45 years old, with atleast one serum sample stored in the DoD
        Serum Repository.
      
Keywords: Testicular Cancer; Epidemiology; Testicular Germ Cell Cancer; TGCT; Healthy Volunteer