Newsroom

Researchers at Columbia University Irving Medical Center and NewYork-Presbyterian have identified two new breast cancer genes. Having one of the genes—MSH6 and PMS2—approximately doubles a woman’s risk of developing breast cancer by age 60.

The study, in collaboration with GeneDx, a genetic testing company, was published online today in Genetics in Medicine.

The two genes were previously known to cause Lynch syndrome, an inherited condition that raises the risk of colorectal, ovarian, stomach, and endometrial cancer. Lynch syndrome is the most common inherited cause of colorectal cancer, accounting for about 3 percent of newly diagnosed cases. One in 440 Americans has a gene variant that causes Lynch syndrome.

Researchers had suspected that Lynch syndrome genes may also cause breast cancer. Some studies had found a link, whereas others had not.

“People with Lynch syndrome aren’t thinking they may also be at risk for breast cancer,” said Wendy Chung, MD, PhD, the Kennedy Family professor of pediatrics (in medicine) at Columbia University Irving Medical Center, clinical geneticist at NewYork-Presbyterian/Columbia, and the study’s senior author. “Given the fact that genomic analysis is becoming more common in patients with a personal or family history of cancer, we have an opportunity to do more targeted breast cancer screening in women who carry any of the genes associated with risk for this disease.”

The researchers analyzed a database of more than 50,000 women who had undergone multi-gene hereditary cancer testing between 2013 and 2015. Of these, 423 women had a mutation in one of the four genes that cause Lynch syndrome: MLH1, MSH2, MSH6, and PMS2.

Additional analyses revealed that women with a mutation in two specific Lynch syndrome genes—MSH6 and PMS2—had a two-fold higher risk of breast cancer compared to women in the general population.

Based on the incidence of cancer in the study population, the researchers calculated that about 31 to 38 percent of women with cancer-causing MSH6 and PMS2 variants will develop breast cancer, compared to around 15 percent of women in the general population.

“The new study suggests MSH6 and PMS2 should be added to the list of genes to screen for when there is a history of breast cancer,” said Dr. Chung, who is also director of the clinical genetics program at NewYork-Presbyterian/Columbia. “Screening for these genes also would give these families potentially life-saving information to prevent colon cancer by encouraging individuals with the genes to increase the frequency of their colonoscopies.”

Currently, testing for Lynch syndrome genes is generally only done when someone has a personal or family history of colon or uterine cancer.

Dr. Chung added, “Given that Lynch syndrome is not rare in the general population, this finding has the potential to impact tens of thousands of people in the U.S. and could change standard practice related to one of the most common cancer predisposition syndromes.”

The study is titled, ‘MSH6 and PMS2 Germline Pathogenic Variants Implicated in Lynch Syndrome are Associated with Breast Cancer.’

Additional authors are Maegan E. Roberts (GeneDx, Gaithersburg, MD), Sarah A. Jackson (GeneDx), Lisa R. Susswein (GeneDx), Nur Zeinomar (Columbia University Mailman School of Public Health, New York, NY), Xinran Ma (Mailman School), Megan L. Marshall (GeneDx), Amy R. Stettner (GeneDx), Becky Milewski (GeneDx), Zhixiong Xu (GeneDx), Benjamin D. Solomon (GeneDx), Mary B. Terry (Mailman School), Kathleen S. Hruska (GeneDx), and Rachel T. Klein (GeneDx).

The study was funded by GeneDx. The authors report no additional conflicts of interest.

Read more about Dr. Chung and her groundbreaking work on Health Matters.

Columbia University Irving Medical Center

Columbia University Irving Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Irving Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cumc.columbia.edu or columbiadoctors.org.

NewYork-Presbyterian

NewYork-Presbyterian is one of the nation’s most comprehensive, integrated academic healthcare delivery systems, whose organizations are dedicated to providing the highest quality, most compassionate care and service to patients in the New York metropolitan area, nationally, and throughout the globe. In collaboration with two renowned medical schools, Weill Cornell Medicine and Columbia University Irving Medical Center, NewYork-Presbyterian is consistently recognized as a leader in medical education, groundbreaking research and innovative, patient-centered clinical care.

NewYork-Presbyterian has four major divisions:

• NewYork-Presbyterian Hospital is ranked #1 in the New York metropolitan area by U.S. News and World Report and repeatedly named to the Honor Roll of “America’s Best Hospitals.”
• NewYork-Presbyterian Regional Hospital Network comprises hospitals and other facilities in the New York metropolitan region.
• NewYork-Presbyterian Physician Services, which connects medical experts with patients in their communities.
• NewYork-Presbyterian Community and Population Health, encompassing ambulatory care network sites and community healthcare initiatives, including NewYork Quality Care, the Accountable Care Organization jointly established by NewYork-Presbyterian Hospital, Weill Cornell Medicine and Columbia.

For more information, visit www.nyp.org and find us on Facebook, Twitter and YouTube.