High blood calcium levels might predict ovarian cancer, the most fatal of the gynecological cancers.
Many ovarian cancers express parathyroid hormone-related protein, which acts to raise calcium levels in serum, which may be a biomarker for ovarian cancer.
Cancer epidemiologists at Wake Forest Baptist Medical Center (Winston-Salem, NC, USA) measured total and ionized serum calcium levels using ion-specific electrodes. They were pH-adjusted because the protein binding of calcium is affected by pH; ionized calcium in blood is commonly corrected to standard pH. Serum samples were collected as part of Third National Health and Nutrition Examination Surveys (NHANES III) between 1988 and 1994 from two nationally representative prospective cohorts.
Eleven ovarian cancer deaths were observed over 95,556 person-years of follow-up through December 31, 2006, representing 137,404 ovarian cancer deaths in the United States of America. The range in total serum calcium in cases was 2.14–2.44 mmol/L and for ionized serum calcium was 1.17–1.31 mmol/L. The normal reference range for total serum calcium is approximately 2.17–2.52 mmol/L and 1.12–1.32 mmol/L for ionized serum calcium. In the second cohort, there were eight ovarian cancer cases in over 31,089 person-years of follow-up. The range of total serum calcium was 1.98–2.93 mmol/L. The relative hazard for fatal ovarian cancer was 1.52 per 0.1 mmol/L increase in total serum calcium and 2.44 per 0.1 mmol/L increase in ionized serum calcium.
Gary G. Schwartz, PhD, the lead author of the study, said "One approach to cancer biomarker discovery is to identify a factor that is differentially expressed in individuals with and without cancer and to examine that factor''s ability to detect cancer in an independent sample of individuals." His coauthor added, "Everyone''s got calcium and the body regulates it very tightly. We know that some rare forms of ovarian cancer are associated with very high calcium, so it''s worth considering whether more common ovarian cancers are associated with moderately high calcium."
The authors concluded that this biomarker, the higher levels of calcium in serum, were significantly positively associated with the risk of ovarian cancer in two prospective cohorts. The principal limitation of this study is the small number of cases. Conversely, the study has several strengths: it is prospective, uses population-based data from two nationally representative cohorts, and is the first to study ionized serum calcium. The existence of stored sera from sample sets of women with and without ovarian cancer should facilitate the confirmation or refutation of the association between serum calcium and ovarian cancer. The study was published January 9, 2013, in the journal Gynecologic Oncology.