Abstract
BackgroundIonized calcium (Ca) and magnesium (Mg) compete as essential messengers to regulate cell proliferation and inflammation. We hypothesized that inadequate Mg levels, perhaps relative to Ca levels (e.g. a high Ca/Mg ratio) are associated with greater prostate cancer risk.Study DesignIn this biomarker sub-study of the Nashville Men's Health Study (NMHS), we included 494 NMHS participants, consisting of 98 high-grade (Gleason≥7) and 100 low-grade cancer cases, 133 prostate intraepithelial neoplasia (PIN) cases, and 163 controls without cancer or PIN at 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 potential confounding factors.ResultsSerum Mg levels were significantly lower, while the Ca/Mg ratio was significantly higher, among high-grade cases vs. controls (p = 0.04, p = 0.01, respectively). Elevated Mg was significantly associated with a lower risk of high-grade prostate cancer (OR = 0.26 (0.09, 0.85)). An elevated Ca/Mg ratio was also associated with an increased risk of high-grade prostate cancer (OR = 2.81 (1.24, 6.36) adjusted for serum Ca and Mg). In contrast, blood Ca levels were not significantly associated with prostate cancer or PIN.Mg, Ca, or Ca/Mg levels were not associated with low-grade cancer, PIN, PSA levels, prostate volume, or BPH treatment.ConclusionLow blood Mg levels and a high Ca/Mg ratio were significantly associated with high-grade prostate cancer. These findings suggest Mg affects prostate cancer risk perhaps through interacting with Ca.
Highlights
Prostate cancer is the most common non-cutaneous malignancy in Western societies and the second leading cause of cancer death in men [1]
Low blood Mg levels and a high calcium to magnesium ratio (Ca/Mg) ratio were significantly associated with high-grade prostate cancer
We further investigated the interaction between magnesium and calcium levels on aggressive or high-grade prostate cancer risk, hypothesizing that inadequate serum magnesium levels reflected by a high serum ratio of calcium to magnesium will be associated with more aggressive prostate cancer
Summary
Prostate cancer is the most common non-cutaneous malignancy in Western societies and the second leading cause of cancer death in men [1]. A number of prospective studies have investigated the relationship between calcium and overall prostate cancer risk, with decidedly mixed results [2,3,4,5,6]. Several studies investigating the relationship between calcium intake and the risk of aggressive or clinically relevant prostate cancers have generated both null [4,6] and positive results [7,8,9,10,11,12,13]. Blood calcium levels are tightly regulated, and only moderately affected by dietary intake of calcium and absorption rate [16]. One possible explanation for the inconsistencies across study populations is that dietary intake measures of calcium may not accurately reflect the blood calcium concentration to which prostate tissue is exposed. We hypothesized that inadequate Mg levels, perhaps relative to Ca levels (e.g. a high Ca/Mg ratio) are associated with greater prostate cancer risk
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