Genetic studies of inherited predisposition to ovarian cancer have tended to focus on women with a known family history of the disease. Now, a new study of ovarian cancer patients with no known family history of the disease found one fifth of them had inherited alterations in genes known to be linked to ovarian and breast cancer.
Writing about their work in Nature Communications, the researchers, from Washington University School of Medicine in St. Louis, MO, say they hope their findings will lead to improved screening methods for ovarian cancer, a disease that strikes around 22,000 women in the US every year - many of whom do not know they have it until it has spread.
Ovarian cancer is hard to detect in the early stages, and it is very difficult to treat once it has spread, with the result that the average 5-year survival rate is as low as 43%.
Symptoms of ovarian cancer are non-specific and can be mistaken for other conditions. They include frequently feeling the need to urinate, pelvic pain and bloating.
First large-scale study of inherited and acquired mutations in ovarian cancer
One cause of cancer is mutations to genes that cause them to behave abnormally. Some mutations are inherited - passed from parent to offspring - while others, known as acquired mutations, can develop over a person's lifetime.
This new study is the first large-scale analysis of the combined effect of inherited and acquired mutations in a major type of cancer.
Senior author Dr. Li Ding, assistant director of The Genome Institute at the School of Medicine, says:
"Using advanced genomic analysis, we found that 20 percent of women with ovarian cancer had inherited mutations in a gene pathway known to be important in inherited breast and ovarian cancer."
She describes the number as "pretty high" and says this suggests "we need to find better ways to screen women for ovarian cancer, even if they don't have family histories of the disease."
Researchers found 222 mutations that increase risk for ovarian cancer
For their study, Dr. Ding and colleagues studied 429 women with sporadic ovarian cancer who did not have a known family history of either ovarian or breast cancer or rare cancer syndromes - all of which are known to increase the risk of developing ovarian tumors.
They analyzed DNA from each woman's tumor tissue and compared it with DNA from her skin. From this comparison, they could identify the acquired mutations in each tumor.
The researchers also compared the patients' skin DNA with that of 557 women without ovarian cancer to identify inherited mutations.
In total, the team found 222 inherited mutations that increase the risk for ovarian cancer. Some were already known about, for instance BRCA1 and BRCA2, while others have never been linked to ovarian cancer.
The inherited gene mutations they found are of the kind that shorten protein-coding sequences, leading to faults in proteins that keep cell division in check and repair faulty DNA - ideal conditions for cancer to develop.
Dr. Ding says the 20% is probably a conservative estimate, since they found a raft of other smaller inherited genetic changes. They are currently working on these to see if they are linked to the development of ovarian cancer, as she explains:
"With more research, we expect to find additional mutations linked to hereditary ovarian cancer."
Funds from the National Cancer Institute and the National Human Genome Research Institute at the National Institutes of Health (NIH) helped to finance the study.
Meanwhile in August 2013, another team of US scientists reported in the journal Cancer that they have developed a screening test that may be able to detect ovarian cancer earlier.
Written by Catharine Paddock PhD