Screening methods for ovarian cancer are urgently needed. Previously, we showed that women who develop ovarian cancer show an increase in serum calcium and a decrease in serum albumin (Schwartz et al, 2020, Gynecol Oncol 2020:159:264-269). These changes could be useful in screening. We asked, prior to their diagnosis, are women with ovarian cancer more likely to show a positive slope in their in albumin-adjusted serum calcium (a-asc)?
This is a population-based case-control study based in Sioux Falls, SD. Cases were women with epithelial ovarian cancer. Controls are women without a diagnosis of cancer. Patients with a history of cancer and/or parathyroid disease were excluded. Data are from patients’ Comprehensive Metabolic Panels (CMPs). We calculated albumin-adjusted serum calcium (a-asc) and estimated regression equations of each woman’s a-asc from pre-diagnosis to diagnosis. Data were analyzed by multiple regression, ANCOVA and logistic regression.
We studied 124 cases and 98 controls. Cases were significantly older than controls (64.7 12.9 SD, vs. 41.0 16.8 years). For controls, the first and last a-asc was 9.23 mg/dL, for a slope of 0. For cases, the first and last values of a-asc were 9.28 and 9.37 mg/dL, for a slope of 0.04 mg/dl per year (P<0.001). The probability of cancer for a 0.04 mg/dL/year increase in a-asc increased with age until age 70 and showed a significant dose-response. The Odd Ratio (OR) of ovarian cancer for a 65 yr old woman with a 0.06 mg/dL increase/year was ∼3.0; the OR for a 1 mg/dl increase/year was ∼10. This effect was also seen for early stage tumors and persisted after age-adjustment.
In health, serum calcium levels are tightly regulated and the “expected” slope of a-asc is zero. A significant positive slope of a-asc in women with ovarian cancer, if confirmed by future studies, suggests that an increase in the slope a-asc could help identify women with undiagnosed ovarian cancer. Increases in a-asc were often small and could be easily overlooked. However, a computer algorithm could calculate the slope from patients’ annual records. Women with rising a-asc could be candidates for increased medical surveillance (e.g., transvaginal ultrasonography).
The authors.
This research was funded by grants from the University of North Dakota School of Medicine & Health Sciences, the Great Plains IDeA-CTR and the Coverys Community HealthCare Foundation (to GGS).
All authors have declared no conflicts of interest.