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Gene studies shed light on women’s reproductive health

Genetics has revolutionized the study of women’s cancers. Now a woman can swab her cheek and learn whether she’s at an elevated risk of developing breast or ovarian cancer. And if she does find a lump in her chest, that woman can take another genetic test to determine whether she’s a good candidate for targeted drug therapy.

Unfortunately, the same can’t be said of most diseases of the female reproductive system that aren’t cancer. The genetics community has largely ignored conditions such as endometriosis, a painful disorder of the uterus, and polycystic ovary syndrome, a leading cause of infertility.

A group of Boston-area researchers is trying to change that. And at the American Society for Human Genetics annual meeting on Wednesday, scientists from the Broad Institute and Harvard Medical School convened the conference’s first panel on gynecologic genetics and genomics, where researchers discussed the latest DNA advances that could revolutionize the diagnosis, management, and treatment of diseases unique to women.

“There is a palpable surge in discussion and enthusiasm,” said panel organizer Stacey Missmer, scientific director of the Boston Center for Endometriosis, a joint clinic of Boston Children’s Hospital and Brigham and Women’s Hospital. “That is a marvelous shift.”


Part of the reason that women’s reproductive diseases have not sufficiently been the subject of studies comes down to funding: The National Institutes of Health spends around $900 million per year on research into breast, ovarian, and uterine cancers but only a small fraction of that on other common women’s health issues that, while not fatal, can still cause debilitating pain, bleeding, pregnancy complications, and other problems.

Last year, endometriosis received only $7 million in NIH research support; uterine fibroids — a type of noncancerous growth — got only $9 million.

Cynthia Morton, a geneticist at Brigham, was one of the few funded to study the genetics of uterine fibroids, which affect about 75 percent of women of reproductive age. With more than a decade of near-continuous funding from the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development, she has pinpointed several bits of DNA tied to increased risk, including some involved with fat production and storage.


Morton spoke on Wednesday about how genetic analyses of large populations can help with treatment plans. “This could lead us to our president’s big plan to have precision medicine,” she said, referring to Obama’s $215 million initiative toward the development of therapies tailored to each patient’s individual profile.

Also at this week’s meeting in Baltimore, Missmer’s Oxford colleague Krina Zondervan presented the results of a 16,000-person study that compared genetic variations in women with and without endometriosis, a disease in which uterine cells travel to other parts of the body and begin to grow. She found that women with the condition often harbor mutations in a gene called WNT4, which plays a role in determining an embryo’s sex.

This finding could help women assess their risks, noted Dr. Joe Leigh Simpson, an expert in gynecological genetics who heads research and global programs at the March of Dimes. If a woman learns she has the WNT4 mutation, she might consider taking birth control pills, which have been shown to slow the development of endometriosis, or she might alter family decisions.

“You might want to accelerate your childbearing if you have a predisposition to endometriosis,” said Simpson, who was not involved in the research.


Genetic insights are also being made into the underpinnings of polycystic ovary syndrome, a problem of hormone imbalance that affects 1 in 10 women. Cecilia Lindgren, an Oxford geneticist and a visiting scientist at the Broad Institute, discussed her study of 87,000 women, which linked many genes that control neurotransmitters with the syndrome.

“The question was whether the brain or the ovary is the dominant organ in the disorder,” Lindgren said. “In our data it looks like it’s both.”

Meanwhile, Dr. Joanne Murabito, a primary care physician at Boston Medical Center, has been probing the genetics of menstruation. From a cohort of nearly 70,000 women, Murabito and her colleagues found 44 regions of the genome linked to the timing of menopause — and what jumped out at her was how many related to DNA repair. “There’ve been some studies in animal models that have shown that the inability to effectively repair DNA can lead to cell death and decline in the eggs and the ovary, and then leads to an earlier menopause,” said Murabito, who published her findings last week in the journal Nature Genetics.

“How that’s going to translate to humans, and how that’s going to translate to human disease,” she added, “those are the next steps in the work.”

Eric Boodman can be reached at eric.boodman@statnews .com. Follow Stat on Twitter: @statnews.

Correction: Because of a reporting error, an earlier version of this story stated that Missmer herself presented at the meeting, instead of her colleague Krina Zondervan, and that the study included 120,000 participants, instead of 16,000.