Healthy Living

How Your Father’s Genes Can Affect Your Ovarian Cancer Risk

New evidence has surfaced, revealing a new genetic mutation that increases a woman’s risk of ovarian cancer that can be passed down through the paternal line by the X chromosome.

It is well known that inherited mutations in BRCA1/BRCA2 genes increase the risk of breast and ovarian cancers, as well as other types of cancer. An altered mutation in the BRCA1 or BRCA2 gene can be inherited from an individual’s mother or father.

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Now, new evidence has surfaced, revealing a new genetic mutation that increases a woman’s risk of ovarian cancer and one that can be passed down through the paternal line by the X chromosome.

To screen or not to screen

For a while now, studies have demonstrated the harms of cancer screenings, including false-positive results leading to surgery and subsequent complications. As a result, a recent study, published in the journal JAMA, aimed to determine whether or not all women should get screened for ovarian cancer, as well as the benefits and harms of such screening among women of average-risk.

The researchers involved in the study examined more than 1000 research papers published between 2003 and 2017 and derived to the conclusion that “ovarian cancer mortality did not significantly differ between screened women and those with no screening or in usual care.” However, they did find that the harms of ovarian cancer screening far outweighed the benefits. Hence, they do not advise women of average-risk to undergo such a procedure.

Dr. Stephanie V. Blank, a professor of gynecologic oncology in the Department of Obstetrics, Gynecology, and Reproductive Sciences at the Icahn School of Medicine at Mount Sinai, commented on this recommendation. “I agree that women who are not at increased genetic risk for ovarian cancer should not be offered ovarian cancer screening because we do not have an effective screening test” she said. She went on to stress that a woman who believes she is at an increased genetic risk for cancer should discuss her options with her doctor so that together, they can determine whether genetic testing and / or screening is appropriate.

Yet, who is more at risk of ovarian cancer?

An all-or-none kind of pattern

Previous studies have found that the sisters of patients with ovarian cancer seem to be at a higher risk of developing this cancer than their mother. It was these findings that led the researchers at Rosewell Park Comprehensive Cancer Center in Buffalo, New York to investigate genes passed down through the paternal line of patients with ovarian cancer.

The study, published in the journal PLOS Genetics, examined evidence on sets of granddaughters and grandmothers by means of the Familial Ovarian Cancer Registry. The registry comprises of data on over 50,000 participants and 5,600 cancers across 2,600 families. “Our study really leveraged this large familial registry that we’ve had running at Roswell Park for over 35 years. The familial cancer registry is, I believe, the oldest ovarian cancer registry in the world” said Kevin H. Eng, lead author of the study and Assistant Professor of Oncology at Roswell Park Comprehensive Cancer Center.

The researchers involved in the study found that ovarian cancer cases associated with genes passed down from the paternal grandmother were strongly linked with early stage cancer (28%), as opposed to ovarian cancer cases associated with genes passed down from the maternal grandmother (14%). They also looked at the X chromosome from 186 individuals with ovarian cancer and discovered a new genetic mutation associated with an increased risk of ovarian cancer.

The research team found that ovarian cancer cases linked to the new genetic mutation develop over 6 years earlier than the average age of onset for ovarian cancer. They also found a link between the new genetic mutation and an increased risk of prostate cancer among male family members.

Regardless, the study was not able to confirm the identity and function of the genetic mutation in question, so the researchers acknowledged that further studies are necessary before deriving to any conclusive findings. “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” said professor Eng. “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” he added.

Eng and his fellow colleagues believe that multiple ovarian cancer cases that appear to be sporadic may, in fact, be genetic. That being said, identifying the cancer-causing genetic mutation responsible could lead to improvement in ovarian cancer screening.

A novel and significant finding

Ovarian cancer can be particularly dangerous because symptoms tend not to present themselves until after the cancer has spread from the ovaries. During this time, the ‘silent killer’ becomes much more difficult to treat, presenting a 46% five-year survival rate.

The discovery made by researchers at the Roswell Park Comprehensive Cancer Center shows that there is still so much to learn about the impact of genetics on cancer risk. “I think that the genes that so far have been discovered are just the tip of the iceberg. There are many other genes that are yet to be discovered, and together that group of genes will compromise a much higher percentage of cancer [causes]” said Dr. Avner Hershlag, Chief of the Northwell Health Fertility in New York.

He stressed that the diagnosis of any gene is possible, but unless the gene is identified, doctors are unable to help. This is why diagnosis of a cancer-causing genetic mutation is of particular importance to the patient. The more information that doctors can give their patients about their cancer risk, the better they can provide them with treatment before and after a cancer diagnosis. “It means a lot in terms of how they manage the rest of their lives, and in terms of what kind of preventative or prophylactic monitoring they do” said Dr. Hershlag.

While this particular finding that fathers can pass down cancer-causing genetic mutations onto their daughters is not new, it can help to improve ovarian cancer screening and detection of the disease at an early stage. Further research may enable more lives to be saved on account of better family history screening questionnaires and eventually, the development of genetic tests may be able to help a new generation before they are even born.

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