Blood Magnesium, and the Interaction with Calcium, on the Risk of High-Grade Prostate Cancer

Ionized 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.In 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.Serum 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.Low 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

Genetic Determinants of Metabolism and Benign Prostate Enlargement: Associations with Prostate Volume

<div><p>Prostate enlargement leading to clinical benign prostatic hyperplasia (BPH) is associated with metabolic dysregulation and obesity. The genetic basis of this association is unclear. Our objective was to evaluate whether single nucleotide polymorphisms (SNPs) previously associated with metabolic disorders are also associated with prostate volume (PV). Participants included 876 men referred for prostate biopsy and found to be prostate cancer free. PV was measured by transrectal ultrasound. Samples were genotyped using the Illumina Cardio-MetaboChip platform. Multivariable adjusted linear regression models were used to evaluate SNPs (additive coding) in relation to natural-log transformed (log) PV. We compared SNP-PV results from biopsy-negative men to 442 men with low-grade prostate cancer with similar levels of obesity and PV. Beta-coefficients from the discovery and replication samples were then aggregated with fixed effects inverse variance weighted meta-analysis. SNP rs11736129 (near the pseudo-gene <i>LOC100131429</i>) was significantly associated with log-PV (beta: 0.16, p-value 1.16x10^-8) after adjusting for multiple testing. Other noteworthy SNPs that were nominally associated (p-value < 1x10^-4) with log-PV included rs9583484 (intronic SNP in <i>COL4A2</i>), rs10146527 (intronic SNP in <i>NRXN3</i>), rs9909466 (SNP near <i>RPL32P31</i>), and rs2241606 (synonymous SNP in <i>SLC12A7</i>). We found several SNPs in metabolic loci associated with PV. Further studies are needed to confirm our results and elucidate the mechanism between these genetic loci, PV, and clinical BPH.</p></div

Genetic Determinants of Prostate Volume at p<1x10^-4 from Meta-analysis Combining Results across Diagnostic Groups: the Nashville Men’s Health Study.

<p>CHR = Chromosome; SNP = Single Nucleotide Polymorphism MA = Minor Allele; RA = Referent Allele; MAF = Minor Allele Frequency; I² = amount of heterogeneity between groups not explained due to chance; Table sorted by Fixed effects P value;</p><p>*SNP is on the intron region of the gene</p><p>**SNP is on the exon region of the gene</p><p>Genetic Determinants of Prostate Volume at p<1x10^-4 from Meta-analysis Combining Results across Diagnostic Groups: the Nashville Men’s Health Study.</p

MetaboChip SNPs Nominally Associated with Natural-log Transformed Prostate Volume at p <1x10^-4 in Men without Prostate Cancer (PC) and Men with Low-grade PC: the Nashville Men’s Health Study.

<p>CHR = Chromosome; SNP = Single Nucleotide Polymorphism MA = Minor Allele; RA = Referent Allele; MAF = Minor Allele Frequency; Beta Coefficient from linear regression model evaluating natural log transformed prostate volume as a continuous dependent variable, while adjusting for age (continuous), body mass index (continuous), height (continuous), and 10 genetic ancestry principal components.</p><p>*SNP is on the gene; but is on the intron region</p><p>MetaboChip SNPs Nominally Associated with Natural-log Transformed Prostate Volume at p <1x10^-4 in Men without Prostate Cancer (PC) and Men with Low-grade PC: the Nashville Men’s Health Study.</p

Study Characteristics of Men without Prostate Cancer (PC) and with Low-grade PC: the Nashville Men’s Health Study.

<p>*p-values from student’s t-test with unequal variances (for comparing group means), or from Mann-Whitney test (for comparing group medians), or Pearson’s chi-squared test (for categorical variables). SD = Standard deviation; IQR = Inter quartile range</p><p>Study Characteristics of Men without Prostate Cancer (PC) and with Low-grade PC: the Nashville Men’s Health Study.</p

Association between Mg, Ca, and Ca/Mg with study population characteristics.

<p>*missing values: waist (n = 1), WHR (n = 1), PSA (n = 4), volume (n = 16).</p><p>**p-value to test for one-way ANOVA testing for differences in Mg, Ca, or Ca/Mg between levels of each factor.</p

Study population description.

<p>Study population description.</p

Association between Mg, Ca, or Ca/Mg with PIN and Prostate Cancer.

<p>Adjusted for age, treatment for diabetes, treatment for CVD, WHR, and race.</p>∧<p>also adjusted for magnesium, calcium, or magnesium and calcium, as appropriate.</p