Broken bones may reduce risk of ovarian cancer

May 10 2005

The pain and suffering of a broken bone may yield an unexpected benefit – a reduced risk of ovarian cancer.

According to a new study reported in the May issue of Cancer Epidemiology, Biomarkers & Prevention, this unlikely pairing of unfortunate life events has a common thread: a protein called MUC1. What's more, this knowledge may offer new insights into a vaccine against ovarian cancer.

The study, conducted by a team of scientists led by Daniel W. Cramer, M.D., Sc.D., a professor in the Department of Obstetrics and Gynecology at Brigham and Women's Hospital in Boston, in collaboration with scientists from the University of Pittsburgh, revealed that events associated with high blood levels of antibodies against this protein generally result in lower incidence of ovarian cancer.

Bone fractures were among seven events or conditions leading to elevated levels of these antibodies. The list includes mastitis during breast feeding, use of an intrauterine device, development of osteoporosis, and several types of gynecological surgery, including tubal ligation, cervical conization and caesarian section.

"Several of these events are already know to reduce risk for ovarian cancer," Cramer said. "Our study offers a new explanation for the protection as well as other events not previously known to reduce ovarian cancer risk."

MUC1 is a protein commonly made by healthy cells that line the reproductive organs, the breast, intestine and airways. Even bone marrow cells that might be released from a bone fracture express MUC1.

Ovarian tumor cells, as well as breast and endometrial cancers, also make MUC1, but the cancer version of the protein lacks much of the glycosylation – the number and extent of carbohydrate side chains seen on healthy cell MUC1. Cancer cells often shed the hypoglycosylated MUC1 protein into the blood, where the body's immune system recognizes the cancer-related protein and generates antibodies against it.

Inflammation, such as that as caused by the events described by Cramer and his colleagues, appears also to promote high levels of cellular MUC1. Their research suggests that the increase in blood levels of MUC1 due to injury or surgery may prompt the immune system to generate antibodies and perhaps immune cells against MUC1, which then can be effective in nipping very early stage ovarian cancer tumors in the bud.

Furthermore, multiple events leading to elevated MUC1 antibodies resulted in correspondingly higher reductions in ovarian cancer risk. Women who experienced two events leading to elevated MUC1 antibody levels were about 30 percent less likely to develop ovarian cancer than women with none or only one MUC1 antibody-promoting event, the study showed. Those that had experienced five of the MUC1 antibody-promoting events had about a 70 percent reduction compared to women with none or only one event.

Olivera J. Finn, Ph.D., professor and chair of the Department of Immunology at the University of Pittsburgh School Of Medicine, known for research in developing cancer vaccines based on MUC1, noted that type of antibodies found in the women studied requires stimulation of certain types of immune cells known as T-cells. Thus it is likely that multiple arms of the immune system may be activated during these events, and participate in the immune protection from cancer.

Besides presenting a new model to explain risk factors for ovarian cancer, Cramer and Finn speculated that the results of this research could lead to the development of preventive vaccines for ovarian and perhaps other cancers that express MUC1. Currently MUC1 vaccines are being tested in cancer patients to treat the cancer or prevent its recurrence.

"Treatment may be more successful earlier in the course of disease or to prevent the disease in the first place in women at high risk for ovarian cancer," said Finn.

Other collaborators in the study with Cramer and Finn are Allison F. Vitonis, M.P.H., Ross S. Berkowitz, M.D., and William Welch, M.D., Brigham and Women's Hospital, Boston; Linda Titus-Ernstoff, Ph.D., Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, N.H, and John McKolanis, Ph.D. University of Pittsburg.