Men who have serum calcium levels in the upper range of normal are at significantly increased risk of fatal prostate cancer, a study found.

If the relationship between serum calcium and fatal prostate cancer turns out to be causal, clinicians may be able to lower patients’ risk of death by prescribing medications or lifestyle changes that reduce serum calcium and parathyroid hormone (PTH), according to researchers.

The study, published in Cancer Epidemiology, Biomarkers & Prevention (2008;17:2302-2305), is the first to examine prostate cancer risk in relation to serum calcium. Researchers found that men in the top tertile of serum calcium (median 10.1 mg/dL) have a 2.7 times higher risk of fatal prostate cancer than men in the bottom tertile (median 9.3), comparable to the risk associated with family history. The finding “could add significantly to our ability to identify men at increased risk for fatal prostate cancer,” the authors wrote.

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“I was a little surprised by the magnitude of the findings because it showed a near tripling in risk,” commented study investigator Gary G. Schwartz, PhD, MPH, associate professor of cancer biology and of epidemiology and prevention at Wake Forest University School of Medicine in Winston-Salem, N.C.

Researchers based their findings on an analysis of data from the first National Health and Nutrition Examination Survey (NHANES I). The study included 2,814 men aged 24-77 years at baseline examinations in 1971-1975. The investigators identified 85 new cases of prostate cancer and 25 prostate cancer deaths that occurred over 46,188 person-years of follow-up. Serum calcium was determined an average of 9.9 years before the diagnosis of prostate cancer. The top tertile had high-normal calcium levels (9.9-10.5). The study found no association between serum calcium and prostate cancer incidence.

Both calcium and PTH have been shown to promote the growth of prostate cancer cells in the laboratory, according to Dr. Schwartz. Serum calcium ordinarily is tightly regulated by PTH, so there is little variation in an individual’s serum calcium over time.

“This study needs to be confirmed, and it can be confirmed relatively quickly because serum calcium is measured routinely. Many data banks have large [collections of] serum calcium levels, for example, from big prostate trials, such as the finasteride trial,” Dr. Schwartz said.

“What is exciting is that calcium is commonly measured and it is cheap to measure. If calcium levels can predict risk of disease, it allows for a new way to prevent disease by lowering them.”

Robert G. Uzzo, MD, chairman of surgical oncology and director of urologic research at Fox Chase Cancer Center in Philadelphia, said these findings may turn out to be clinically significant but it is too early to draw conclusions from just one study.

“The data are intriguing, but I do not believe they are powerful enough to suggest that lowering serum calcium levels can decrease the risk of fatal prostate cancer,” said Dr. Uzzo, medical director for Renal & Urology News.

“Equally important to practicing urologists is that the data, again while hypothesis-generating, are not hypothesis-testing. These data may prove interesting to urologists and may cause them to look at serum calcium levels, which are often measured in comprehensive metabolic profiles, but I do not think that high-normal calcium levels would prompt intervention in the absence of other indications.”