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Study Shows 20% of Women With Ovarian Cancer Have Inherited Genetic Mutations That Increase Risk of Disease

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Key Points

  • A genetic analysis of 429 women with ovarian cancer with no known family histories of breast or ovarian cancer has found that one-fifth of them had inherited alterations in genes known to be associated with these cancers.
  • According to the researchers, 37% of women with ovarian cancer had either inherited or acquired mutations in the Fanconi anemia pathway.
  • The findings could lead to the development of better screening strategies for ovarian cancer and improved earlier detection.

A large-scale genetic analysis of women with ovarian cancer with no known family histories of breast or ovarian cancer has found that one-fifth of them had inherited alterations in genes known to be associated with these cancers. The findings could lead to the development of better screening strategies for ovarian cancer and improved earlier detection. The study is published in Nature Communications.

Earlier studies have investigated inherited susceptibility to ovarian cancer, but they have focused on women with a known family history of the disease. In the current study, researchers from Washington University School of Medicine in St. Louis, Missouri, studied 429 women with ovarian cancer that appeared to develop sporadically. None of the women had known family histories of breast or ovarian cancer or rare cancer syndromes, all of which can increase the risk of developing ovarian tumors. The women ranged in age from 26 to 89, and 90% were Caucasian.

Study Methodology

The researchers performed a genetic analysis of each woman’s tumor and DNA taken from a skin sample. They compared the genetic sequences side-by-side and identified the acquired mutations in individual tumor samples. They then compared the patients’ DNA samples with the DNA of a control group of 557 women who did not have ovarian cancer.

Study Findings

The researchers identified 222 inherited genetic variants that increase the risk of ovarian cancer. Some variants occurred in genes already linked with a genetic predisposition to ovarian cancer, such as BRCA1 and BRCA2, while others occurred in genes that had not previously been associated with the cancer. The inherited gene mutations identified were the kind that shorten protein-coding sequences, disrupting the function of key proteins, such as those that keep cell division in check or repair mistakes in DNA.

Twenty percent of the women in the study had inherited mutations in a pathway of genes associated with Fanconi anemia, a rare, hereditary bone marrow disease. These genes are involved in DNA repair and have been linked to certain cancers, including breast and ovarian tumors. According to the researchers, 37% of women with ovarian cancer had either inherited or acquired mutations in the Fanconi anemia pathway. Women with inherited mutations in this pathway were also more likely to be diagnosed with ovarian cancer at a younger age.

“Using advanced genomic analysis, we found that 20% of women with ovarian cancer had inherited mutations in a gene pathway known to be important in inherited breast and ovarian cancer. That number seems pretty high. This tells us that we need to find better way to screen women for ovarian cancer, even if they don’t have family histories of the disease,” Li Ding, PhD, Assistant Director at The Genome Institute at the School of Medicine, research member of the Siteman Cancer Center, and a senior author of the study, said in a statement. “With more research, we expect to find additional mutations linked to hereditary ovarian cancer. Thus, 20% is a conservative estimate.”

According to the National Cancer Institute, ovarian cancer accounts for approximately 3% of all cancers in women and is the fifth leading cause of cancer-related death among women in the United States. In 2013, more than 22,000 women were diagnosed with ovarian cancer and approximately 14,000 died.

Dr. Deng is the corresponding author for the Nature Communications article.

This study was funded by the National Cancer Institute and the National Human Genome Research Institute at the National Institutes of Health. The study authors reported no potential conflicts of interests.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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