Ovarian cancer: Calcium levels could detect disease, study hints

February 7, 2013 | by Roberta Nichols

Ovarian cancer remains one of the deadliest – and hardest-to-cure – diseases, stealthily metastasizing before women are even diagnosed. Last year, 15,500 women died of the disease and 22,280 new cases were diagnosed, according to the National Cancer Institute. Now some researchers are suggesting that blood calcium levels may one day help detect ovarian cancer.

Ovarian cancer is often not detected until it's metastisized. New research suggests blood calcium levels might provide a clue to the disease. Shown here: the female reproductive system, with the ovaries to the left and right. Ovarian cancer is often not detected until it's metastisized. New research suggests blood calcium levels might provide a clue to the disease. Shown here: the female reproductive system, with the ovaries to the left and right.

“Higher serum calcium may be a biomarker of ovarian cancer,” concluded a new study in the journal Gynecologic Oncology. “This is the first report of prospective positive associations between indices of calcium in serum and ovarian cancer.”

Before launching the study, the authors had noted that many ovarian cancers express parathyroid hormone-related protein, which raises blood calcium levels. So, they hypothesized, perhaps high calcium levels might be used as an indicator of ovarian cancer – even at a very early stage.

Their findings suggest there's something to the hypothesis. And, although no one is saying an effective screening method has been found,  researchers and physicians are taking notice of the results.

Lead author Gary G. Schwartz, Ph.D, a cancer epidemiologist at Wake Forest School of Medicine in Winston-Salem, N.C., and his colleague, Halcyon G. Skinner, Ph.D., M.P.H., from the University of Wisconsin Carbone Cancer Center, tested their hypothesis using previously gathered data on serum calcium. To do so, they used two nationally representative – and data-rich – prospective cohorts: the Third National Health and Nutrition Examination Surveys (NHANES III) and the NHANES Epidemiologic Follow-up Study (NHEFS).

According to the researchers, there were 11 deaths from ovarian cancer over 95,556 person-years of follow-up in NHANES III. After parsing the numbers, they found that the risk for fatal ovarian cancer was 52 percent higher for each 0.1 mmol/L increase in total serum calcium and 144 percent higher for each 0.1 mmol/L increase in ionized serum calcium. Associations persisted despite adjusting for complicating factors, such  the use of oral contraceptives.

They also found that eight incident ovarian cancers occurred over 31,089 person-years of follow-up in the NHEFS. After crunching the numbers further, they found a 63 percent higher risk for ovarian cancer with each 0.1 mmol/L increase in total serum calcium. Similar results were observed for albumin-adjusted serum calcium.

Schwartz and Skinner conceded that the findings will require confirmation through other studies  – and Robert Morgan, M.D., co-director of the Gynecological Oncology/Peritoneal Malignancy Program at City of Hope, wholeheartedly agreed.

Morgan stressed the need for validation from other studies, saying a screening test would need to be very sensitive and very specific, lest it lead to false positives and unncecessary surgeries.

“We have been looking for biomarkers to enable early detection of ovarian cancer, and this study shows a connection between blood calcium levels in patients who developed ovarian cancer later who had higher levels and those who did not. But how to use this information is the question,” said Morgan, who was not involved in the Wake Forest study.

“The values of calcium levels were generally normal and the numbers of cases was very small. This information alone will not help us diagnose ovarian cancer early," Morgan said in explaining the limitations of the findings. "However, other biomarkers have been suggested to show changes over time that might be more predictive of ovarian cancer than an individual single level."

He pointed to data suggesting that levels of the protein CA125, even when total values are normal, might rise over time. Such a pattern might be more indicative of malignancy than any single measurement, he added.

"Perhaps an algorithm can be generated that can take many of these single observations which by themselves are not helpful, and put them together in a way that can be more predictive," Morgan said. “The main problem with ovarian cancer remains that the illness is quite uncommon, and the diagnostic testing necessary to make the diagnosis of early disease requires surgery with the potential of harm."

He concluded: “The test that would cause a recommendation for surgery has to be sufficiently sensitive and specific for the numbers of false positives in relation to true positives to suggest a benefit despite the number of unnecessary surgeries that have to be done to follow up on the results.”

Now for the follow-up research.

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