Genetic intersection of male infertility and cancer

Abstract

Recent epidemiological studies have identified an association between male factor infertility and increased cancer risk, however, the underlying etiology for the shared risk has not been investigated. It is likely that much of the association between the two disease states can be attributed to underlying genetic lesions. In this article we review the reported associations between cancer and spermatogenic defects, and through database searches we identify candidate genes and gene classes that could explain some of the observed shared genetic risk. We discuss the importance of fully characterizing the genetic basis for the relationship between cancer and male factor infertility and propose future studies to that end.

Keywords: Cancer; genetics; male infertility.

Figure 1. Identification of candidate genes associated with susceptibility to male infertility and cancer

Human homologs to mouse male infertility genes were intersected with a curated list of known cancer genes (the COSMIC “classic” list). The observed overlap of 25 genes is highly non-random: there is a five-fold enrichment of COSMIC cancer genes in the MGI male infertility list compared to genes that are not on the MGI list (4.7% versus 0.95%, OR=5.12, p< 5 × 10⁻¹⁰ by Fisher Exact Test). We further characterized these 25 candidates by their putative role in cancer. Vogelstein classification of cancer driver genes from (33).