Ionized calcium (Ca) is an essential regulator of cell proliferation, apoptosis, and inflammation; and prior studies suggest increased Ca is associated with prostate cancer. On the other hand, magnesium (Mg) competes with Ca for intestinal absorption and kidney reabsorption. High ionized Mg levels may inhibit, while Mg deficiency may potentate, over 300 physiologic processes regulated by Ca. We hypothesized that inadequate Mg levels, perhaps relative to Ca levels (e.g. a high Ca/Mg ratio) would be associated with lower prostate cancer risk.

The Nashville Men's Health Study utilizes a rapid recruitment, multi-centered protocol to target men over age 40 years and referred for prostate biopsy in Nashville, TN. Study design and data collection permit control for factors related to healthcare access, screening, and detection. From over 2,200 participants, we created a biomarker sub-study of 494 subjects including high-grade (Gleason = 7(4+3), 8,9,10; n=98) and low-grade (Gleason = 6; n=100) cancer, prostate intraepithelial neoplasia (PIN: n=133), and biopsy-negative controls (n=163); frequency matched by 5-year age intervals. Blood was collected prior to prostate biopsy. Linear and logistic regression were used to determine associations between blood Ca, Mg, and the Ca/Mg ratio across controls and case groups while adjusting for age, BMI, WHR, race, prior diabetes, CVD, BPH, and NSAID use.

Blood Mg and Ca levels were not associated with PSA levels or prostate volume. However, adjusted blood Mg levels were significantly lower among high-grade cases vs. controls (Mg: 2.01 vs. 2.08 mg/dl, p=0.03, respectively). Ca levels did not significantly differ between groups, however the Ca/Mg ratio was significantly higher among high-grade cases compared to controls (4.99 vs. 4.77, p=0.01, respectively). Lower blood Mg (lowest tertile) was significantly associated with a 2-fold increased risk of a high-grade disease (T3 (ref), T2: OR=1.42 (0.73, 2.77), T1: OR=1.98 (1.00, 3.94), p-trend = 0.05). Mg levels were not associated with low-grade cancer or PIN, and Ca levels were not significantly associated with caner or PIN. However, increasing Ca/Mg ratio levels were associated with risk of high-grade prostate cancer (T1 (ref). T2: OR=1.47 (0.75, 2.89), T3: OR=1.61 (0.81, 3.20)), and Ca/Mg as a continuous covariate was significantly associated with high-grade disease (OR=1.72 (1.13, 2.61)). High Mg levels (top 50%) were significantly associated with a decreased risk of high-grade disease among men with higher Ca levels (top 50%) (OR=0.41, (0.20, 0.88)), but was not significantly associated with high-grade disease among men with low Ca levels (OR=0.86 (0.38, 1.92)).

In summary, blood Mg levels were significantly lower among men with high-grade prostate cancer, particularly among men with high blood Ca levels. These findings suggest Mg interacts with Ca to affect prostate cancer risk.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2814.