Ovarian Cancer in Women Linked To Mutations in Gene Passed on From Dad

Mutations passed from the X-chromosome of the father can increase the risk of ovarian cancer in daughters and prostate cancer in sons. In earlier studies, researchers noticed that when a woman develops ovarian cancer, her sister faces a higher risk of also developing the disease than her mother, an observation they found difficult to explain.

Using the Familial Ovarian Cancer Registry, a donor-funded resource based at Roswell Park, the researchers collected information about pairs of granddaughters and grandmothers and sequenced portions of the X-chromosome from 186 women affected by cancer. They found that cases of ovarian cancer linked to genes inherited from the paternal grandmother had an earlier age-of-onset than cases linked to maternal genes, and were also associated with higher rates of prostate cancer in fathers and sons.

Additional sequencing led the researchers to identify a previously unknown mutation on the X-chromosome that may be associated with cases of ovarian cancer that develop more than 6 years earlier than average.

The study proposes that a gene on the X-chromosome may contribute to a woman's risk of developing ovarian cancer, independently of other known susceptibility genes, such as the BRCA genes.

Future studies will be needed, however, to confirm the identity and function of this gene. This observation suggests that there may be many cases of seemingly sporadic ovarian cancer that are actually inherited, and may lead to improved cancer screening and better genetic risk assessment.

"Our study may explain why we find families with multiple affected daughters: because a dad's chromosomes determine the sex of his children, all of his daughters have to carry the same X-chromosome genes," says Eng, an assistant professor of oncology in Roswell Park's Department of Biostatistics and Bioinformatics.

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“What we have to do next is make sure we have the right gene by sequencing more families. This finding has sparked a lot of discussion within our group about how to find these X-linked families. It's an all-or-none kind of pattern: A family with three daughters who all have ovarian cancer is more likely to be driven by inherited X mutations than by BRCA mutations."

Source-Eurekalert