WebMD Medical News
Brenda Goodman, MA
Laura J. Martin, MD
Aug. 17, 2011 -- Researchers say they've discovered a marker that could one day help doctors spot women who may be at high risk for ovarian cancer.
The marker is an antibody to a protein, called mesothelin, which is overproduced by cancer cells.
The study found the antibody was present in high levels in the blood of many women who were infertile because of problems with their ovaries.
Researchers think elevated antibody levels may indicate that the body's immune system is attacking its own ovaries, a condition called autoimmune oophoresis.
Autoimmune oophoresis is known to cause infertility, and researchers think it may also lead to some cases of ovarian cancer, though it's not clear how.
"That's the 64 million dollar question," says study researcher Judith L. Luborsky, PhD, professor of pharmacology, obstetrics and gynecology and preventive medicine at Rush University Medical Center in Chicago.
"The question we don't have an answer to is what role the immune system actually plays in the initiation [of cancer]," she tells WebMD.
While the idea is interesting, experts who were not involved in the research say the study only looked at one moment in time, so it's tough to draw conclusions about what elevated antibody levels may mean and it doesn't prove that elevated antibodies cause cancer.
"It sort of creates another hypothesis," says Mary Daly, MD, PhD, professor and chair of the department of clinical genetics at Fox Chase Cancer Center, in Philadelphia.
"There's a lot of literature linking infertility with an increased risk for ovarian cancer, but very little to suggest why that would be," Daly says. "What is it about women who have problems getting pregnant that puts their ovaries at increased risk for ovarian cancer?"
This study may help to direct research into one of the possible explanations for that, she says.
For the study, which is published in the journal Cancer Epidemiology, Biomarkers & Prevention, researchers looked for the antibody in the blood of women who were unable to conceive a baby after a year of unprotected sex, a clinically accepted definition of infertility.
The women were rendered infertile by a variety of conditions, including endometriosis, premature ovarian failure, and irregular ovulation, and in cases where the infertility was unexplained.
Research has shown that women who are infertile face two to four times the odds of getting ovarian cancer, though the reason for the connection is not fully understood.
In its early stages, ovarian cancer has few symptoms. By the time most women are diagnosed, the disease is often advanced and odds of survival are poor.
"We're trying to detect the occurrence of these tumors extremely early." Luborsky says. "We believe there are early signs."
Researchers compared the antibody levels of women with infertility to the levels found in the blood of women with no fertility problems, those with benign tumors or cysts, and those with ovarian cancers.
Significant antibody levels were found in women with ovarian problems, unexplained infertility, and those with cancer, but not in women who were healthy, those who had endometriosis, or those with benign disease.
Researchers say their results suggest that the antibodies to mesothelin may help pick out a group of women at risk for a particular kind of ovarian tumor, called a serous tumor.
Women with endometriosis usually get a different kind of ovarian cancer, called an endometrioid tumor.
"The findings are consistent with the fact that this particular marker we chose is possibly predicting serous ovarian cancer, which is the most nasty, aggressive kind," Luborsky says.
More research is needed to help explain why elevated antibodies may increase a woman's risk of cancer.
But if ovarian cancer does prove to have an autoimmune component, Luborsky says it could one day be possible to give a woman at risk a drug that could reduce her risk of ovarian cancer by turning off the immune attack.
"The endpoint of that would be to ask if we could interrupt that process and prevent cancer," she says.
SOURCES:Luborsky, J. Cancer Epidemiology, Biomarkers & Prevention, Aug. 16, 2011.Judith L. Luborsky, PhD, professor of pharmacology, obstetrics and gynecology, and preventive medicine, Rush University Medical Center, Chicago.Mary Daly, MD, PhD, professor; chair, department of clinical genetics, Fox Chase Cancer Center, Philadelphia.
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