Genetic variants key to understanding origins of ovarian cancer

The discovery of three genetic variants associated with mucinous ovarian carcinomas (MOCs) offers the first evidence of genetic susceptibility in this type of ovarian cancer. The research, published in Nature Genetics (2015; doi:10.1038/ng.3336), also suggests a link between common pathways of development between MOCs and colorectal cancer and for the first time identifies a gene called HOXD9, which turns genes on and off, and provides clues about the development of MOCs.

“It remains a mystery where these cancers come from,” said Simon Gayther, PhD, professor in preventive medicine, Keck School of Medicine of the University of Southern California in Los Angeles and corresponding author of the international genome-wide association study (GWAS). “By finding these genetic markers, we begin to understand more about the biology of the disease itself. This study tells us more about the biology of ovarian cancer from the early development stage than most research has.”

Ovarian cancer is the fourth leading cause of cancer in American women and seventh most common cancer in women throughout the world. In 2015, more than 14,000 American women will die of ovarian cancer, according to the American Cancer Society.

Most ovarian cancers have low survival rates, typically because of the misunderstanding of symptoms and discovery of the cancer in later, less treatable stages.

“Although MOCs are a less common type of ovarian cancer with generally good prognosis when diagnosed in early stages, they are twice as likely to be resistant to treatment at later stages,' said senior author Andrew Berchuck, MD, director of gynecologic oncology at Duke University Cancer Institute in Durham, North Carolina. “Our results will contribute to the identification of women at greatest risk of developing the disease with the long-term goal of prevention.”

The association analysis was based on 1,644 women with MOC and more than 21,000 women without ovarian cancer. The research was conducted as part of the Collaborative Oncological Gene-environment Study (COGS), launched in 2009 with the goal of determining risks of breast, ovarian, and prostate cancer. The study pooled data from more than 40 international studies of ovarian cancer.

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