Abstract 871: A stratified genetic risk assessment for testicular cancer

Abstract

Abstract Three recent genomewide association studies (GWAS) of testicular germ cell tumors (TGCT) have uncovered predisposition alleles in or near several genes including KITLG, BAK1, SPRY4, TERT, ATF7IP and DMRT1. A candidate study has identified the so-called AZFc region as another risk locus on chromosome Y. We used a statistical approach to dissect the question of whether TGCT risk alleles can be utilized in the clinical setting. We employed the receiver operating characteristic curves for genetic risk models to measure the discriminatory power of a genetic risk model. The newly-discovered variants provided a discriminatory power of 69.2%, which was considerably higher than for other cancers analyzed with this method. This suggested that about 69.2% of the time, a randomly-selected patient with TGCT had a higher estimated risk than the risk for a randomly-selected control subject. Using a multiplicative model, we estimated that white men in the top 1% of genetic risk had a relative risk that was 10.5-fold greater than that for the general white male population in the US. Under the assumption that clinical risk factors such as cryptorchidism are not correlated with TGCT risk variants and do not interact with the TGCT loci as contributors to TGCT risk, white men aged 30-34 years with a history of cryptorchidism who were in the top 1% of genetic risk had an estimated 5-year risk of 4.4%. Other clinical risk factors such as family history and infertility could be also used in a stratified genetic risk assessment approach. Extensive statistical modeling and additional genotyping is required before such accurate risk estimates are feasible. We conclude that a genetic risk assessment is not justified in the general population at this time. However, a stratified genetic risk assessment strategy may be useful for men who have independent clinical risk factors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 871. doi:10.1158/1538-7445.AM2011-871