Is There A Hereditary Link Between Testicular And Ovarian Cancer?

Our research group at Roswell Park Comprehensive Cancer Center, led by Kirsten Moysich, PhD, MS, is specifically interested in studying risk factors involved in the development of ovarian cancer, from genetic and modifiable risk factors to comorbidities and family histories of other cancers.

Using data from the Familial Ovarian Cancer Registry at Roswell Park, we were able to thoroughly evaluate the family history of cancers, including testicular cancers, among 2,636 families with multiple cases of ovarian cancer. We observed that mothers of men with testicular cancer in the registry were 3.32 times more likely to have ovarian cancer than mothers of men with other cancers. Likewise, sisters of these men with testicular cancer were more likely to have ovarian cancer than sisters of men with other cancers.

These findings are particularly interesting given recent research from our group reporting a novel ovarian cancer susceptibility gene on the X chromosome. This putative X-linked ovarian cancer susceptibility gene is located on a specific region of the X chromosome, Xq27, previously recognized as a likely candidate gene associated with testicular cancer known as TGCT1. Due to limitations in study design, researchers have previously only been able to identify the region on the X chromosome where this TGCT1 gene exists (Xq27) but have been unable to specifically identify the gene.

Given this new empirical evidence for an association between ovarian cancer and testicular cancer and our recent report of an ovarian cancer susceptibility gene located on the X chromosome in a region previously implicated with testicular cancer, it is possible that this gene may be contributing to the development of both cancer types.

To investigate whether our observed association between familial ovarian and testicular cancers could be attributed to the X chromosome, we turned to an analysis of grandparents of men with testicular cancer in the registry. Because fathers cannot pass their X chromosome to their sons, paternal grandmothers can never pass their X chromosome to their grandsons. Maternal grandmothers, however, can pass their X chromosome to their daughter and, subsequently, to their grandsons.  Knowing this, we assessed the relative frequency of ovarian cancers in paternal and maternal grandmothers of men with testicular cancer. Exactly as would be expected under an X-linkage model, 0% of paternal grandmothers and 25% of maternal grandmothers of men with testicular cancer had ovarian cancer.

Although this evidence is highly compelling, we were unable to conclusively establish X-linkage due to limitations in sample size. Because families with multiple cases of ovarian cancer and testicular cancer are uncommon, we were only able to identify 31 such families in the registry. We are thus currently enrolling families with multiple cases of ovarian and testicular cancers in an effort to increase our sample size and conduct follow-up studies to investigate the specific genetic underpinning of our observed association.

If your family meets these criteria, please consider contacting the Familial Ovarian Cancer Registry for more information on how you can help contribute to our exciting research aimed at better understanding and treating these familial cancers. For more information, please see www.ovariancancer.com.

These findings are described in the article entitled Hereditary association between testicular cancer and familial ovarian cancer: A Familial Ovarian Cancer Registry study, recently published in the journal Cancer Epidemiology. This work was conducted by John Lewis Etter, Kevin Eng, Rikki Cannioto, Jasmine Kaur, Hani Almohanna, Emad Alqassim, J. Brian Szender, Janine M. Joseph, Shashikant Lele, Kunle Odunsi, and Kirsten B. Moysich from Roswell Park Comprehensive Cancer Center.

John Lewis Etter is a graduate student in the MD/PhD joint degree program at the University at Buffalo working under the advisement of Kirsten Moysich, PhD, MS, of Roswell Park Comprehensive Cancer Center.