Testicular Cancer
Testicular Germ Cell Tumors Genetic Admixture Study
In almost all countries with more than one racial/ethnic group, men of European descent are at higher risk of TGCT than are men of non-European descent, particularly men of African descent. Men of European ancestry in the U.S. have incidence rates of TGCT that are approximately seven times higher than incidence rates among African-American men. Whether the disparity is due to variability of environmental exposures or genetic differences, or a combination of the two, is not clear. However, the varying risks of different racial/ethnic groups living in one country suggest that genetic susceptibility may play a role. To better understand racial/ethnic variability in rates, we are conducting a genetic admixture study among African-American TGCT patients. As TGCT is much more prevalent in European-derived than in African-derived populations, the admixture approach can identify regions of unexpectedly high European-ancestry in African-American men with TGCT. These peaks of European chromosomal ancestry would identify underlying TGCT risk loci, because of underlying linkage disequilibrium between the ancestry informative SNP and any TGCT-causing genetic variant(s) with large differences in allele frequencies between the ancentral populations. To conduct this genetic admixture study, we are collaborating with a number of investigators at institutions across the U.S. Collaborators are contributing formalin-fixed, paraffin-embedded pathology blocks from which DNA is being obtained. More information, Katherine McGlynn.
Testicular Cancer among Military Servicemen: the STEED Study
Testicular germ cell cancer has been increasing among men during most of the 20th century. Despite this increase, the etiology of testicular cancer is poorly understood. To better understand the molecular epidemiology of testicular cancer, the National Cancer Institute and the Department of Defense are conducting a case-control study of testicular cancer among military servicemen. The project includes obtaining biosamples and questionnaire data from all participants. Pre-diagnostic serum samples are available from the approximately 1,100 cases and 1,100 controls enrolled in the study. Mothers of all participants are also invited to participate by donating a biosample and responding to a questionnaire. More information, Katherine McGlynn.
Testicular Germ Cell Tumor Study of Viral Etiology
From extensive systematic review and meta-analysis of pre- and peri-natal variables in relation to TGCT, we identified inverse associations with birth-order and sibship size in relation to TGCT. In addition, it is known that there is an increased risk of testicular cancer in men of affected brothers. These observed associations may indicate an infectious etiology. We are currently conducting a small pilot study of a viral chip which tests for the presence of 655 human viruses. We have extracted RNA from 24 Caucasian TGCT specimens, all of which were snap-frozen from fresh. The results from this pilot may be extended into a larger study. More information, Michael Cook.
Testicular Germ Cell Tumor Methylation Study
The heritability of TGCT is high, with studies suggesting TGCT risks of eight-fold in brothers and four-fold in fathers of affected men, compared to men in the general population. However, genome-wide association studies of single-nucleotide polymorphisms have found limited heritable risk. In addition to TGCT being a complex genetic disease, with many alleles contributing small changes in risk, heritable risk could also manifest itself in DNA methylation which can affect gene expression. Recent studies examining genes involved in tumor suppression or cell-cycling have suggested there may be differences in methylation patterns between normal and TGCT tissue. At the National Cancer Institute, we have the opportunity to use a high-throughput assay to assess methylation across 800 genes. This study will compare the methylation profiles of specific TGCT histologies, such as seminoma, embryonal carcinoma and teratoma, with one another and with adjacent ‘normal’ tissue. This agnostic and powerful approach may provide clues into the etiology of TGCTs. More information, Michael Cook.
