Laboratory studies have demonstrated that vitamin D has a number of chemopreventive properties, and that these properties may be mediated or modified by other molecules in the vitamin D pathway, such as parathyroid hormone (PTH) or calcium. However, there is little epidemiologic data exploring the effects of vitamin D on breast cancer risk in the context of these other molecules. We examined a panel of molecules in the vitamin D pathway in relation to mammographic breast density, a marker of breast cancer risk, in the Wisconsin Breast Density Study. A total of 238 postmenopausal women (ages 55-70, with no history of postmenopausal hormone use) were enrolled from mammography clinics in Madison, Wisconsin. Subjects provided blood samples that were analyzed for levels of 25-hydroxy vitamin D [25(OH)D], PTH, insulin-like growth factor-1 (IGF1), IGF-binding protein 3 (IGFBP3), retinol, and calcium. Percent breast density was measured using Cumulus software. In age-adjusted analyses there was a positive association between 25(OH)D and percent breast density (P=0.05; mean percent density=11.3% vs. 15.6% for 1st vs. 4th quartile of 25(OH)D). Breast density was inversely associated with PTH (P=0.05; 16.0% vs. 11.4% for Q1 vs. Q4) and positively associated with the IGF-1:IGFBP-3 molar ratio (P=0.02; 11.9% vs. 15.6% for Q1 vs. Q4). However, these associations were all null after further adjustment for body mass index (BMI; P>0.25). The independent relation between 25(OH)D and breast density remained null among subgroups defined by BMI and serum levels of retinol, calcium, and estradiol. These results suggest no strong independent associations between the circulating molecules of the vitamin D pathway and mammographic breast density in postmenopausal women. While it remains possible that vitamin D could influence breast cancer risk, our results suggest that such an effect would be mediated through pathways other than breast density.

Experimental and clinical data implicate calcium and parathyroid hormone (PTH) in the development of prostate cancer. However, epidemiologic data on the role of these variables in prostate health are sparse. We examined the relationship between serum levels of calcium, PTH and Prostate-Specific Antigen (PSA), an established marker of prostate growth, in a large, population-based study using multivariate linear regression. We studied 895 men in NHANES 2005–2006 who were ≥ 40 years of age and who were without clinical prostate cancer. Adjusted for age, race, BMI and serum levels of 25-Hydroxyvitamin D, serum levels of PTH were significantly positively correlated with serum PSA (P = 0.01). Serum levels of PTH and calcium each were correlated significantly with free PSA (P = 0 .05 and 0 .008, respectively). The percentage of men who had elevated serum levels of PTH (PTH ≥ 66 pg/mL) was significantly greater among African American men (19.2 vs. 9.6%. , P = 0.04). Compared to men whose PTH was at the lower end of the reference range, the predicted PSA for men with a PTH of 66 pg/mL was increased 43%. These findings support the hypothesis that serum calcium and serum PTH stimulate prostate growth in men without clinical prostate cancer and have implications for the use of PSA as a screening tool for prostate cancer.

Background

Several observational studies have recently suggested an inverse association of circulating levels of vitamin D with blood pressure. These findings have been based mainly on Caucasian populations; whether this association also exists among Hispanic and African Americans has yet to be definitively determined. This study investigates the association of 25-hydroxyvitamin D (25[OH]D) with blood pressure in Hispanic and African Americans.

Methods

The data source for this study is the Insulin Resistance Atherosclerosis Family Study (IRASFS), which consists of Hispanic- and African-American families from three U.S. recruitment centers (n=1334). A variance components model was used to analyze the association of plasma 25[OH]D levels with blood pressure.

Results

An inverse association was found between 25[OH]D and both systolic (β for 10 ng/mL difference= −2.05; p<0.01) and diastolic (β for 10 ng/mL difference= −1.35; p<0.001) blood pressure in all populations combined, after adjusting for age, sex, ethnicity and season of blood draw. Further adjustment for body mass index (BMI) weakened this association (β for 10 ng/mL difference= −0.94; p=0.14 and β for 10 ng/mL difference = −0.64; p=0.09, respectively).

Conclusions

25[OH]D levels are significantly inversely associated with blood pressure in Hispanic and African Americans from the IRASFS. However, this association was not significant after adjustment for BMI. Further research is needed to determine the role of BMI in this association. Large, well-designed prospective studies of the effect of vitamin D supplementation on blood pressure may be warranted.

We recently reported a significant positive association in NHANES I between high levels of total calcium in serum, measured prospectively, and risk of fatal prostate cancer (Cancer Epidemiol Biomarkers Prev 2008;17:2302-5). In an attempt to confirm this association, we examined associations between total and ionized serum calcium and prostate cancer mortality in an independent cohort, NHANES III. Twenty-five prostate cancer deaths occurred over 56,625 person-years of follow-up. Compared to men in the lowest tertile of total serum calcium, the multivariate-adjusted relative risk for death from prostate cancer for men in the highest tertile was 2.07 (95% Confidence Interval, C.I.: 1.06 – 4.04). For ionized serum calcium, the physiologically active fraction of total serum calcium, the relative risk for men in the highest tertile was 3.18 (95% C.I. 1.09 – 9.28). These findings support the hypothesis that serum calcium is a prospective biomarker of fatal prostate cancer.

Background

Genome-wide association studies are often limited in their ability to attain their full potential due to the sheer volume of information created. We sought to use the random forest algorithm to identify single-nucleotide polymorphisms (SNPs) that may be involved in gene-by-smoking interactions related to the early-onset of coronary heart disease.

Methods

Using data from the Framingham Heart Study, our analysis used a case-only design in which the outcome of interest was age of onset of early coronary heart disease.

Results

Smoking status was dichotomized as ever versus never. The single SNP with the highest importance score assigned by random forests was rs2011345. This SNP was not associated with age alone in the control subjects. Using generalized estimating equations to adjust for sex and account for familial correlation, there was evidence of an interaction between rs2011345 and smoking status.

Conclusion

The results of this analysis suggest that random forests may be a useful tool for identifying SNPs taking part in gene-by-environment interactions in genome-wide association studies.

We examined the association between serum calcium levels and the risk for prostate cancer using a prospective cohort, the National Health and Nutrition Examination Survey (NHANES) and the NHANES Epidemiologic Follow-up Study (NHEFS). Eighty five incident cases of prostate cancer and twenty five prostate cancer deaths occurred over 46,188 person-years of follow-up. Serum calcium was determined an average of 9.9 years prior to the diagnosis of prostate cancer. Comparing men in the top to men in the bottom tertile of serum calcium, the multivariable adjusted relative hazard for fatal prostate cancers was 2.68 (95% Confidence Interval 1.02-6.99; Ptrend = 0.04). For incident prostate cancer, the relative risk for the same comparison was 1.31 (95% C.I. 0.77-2.20; Ptrend=0.34). These results support the hypothesis that high serum calcium or a factor strongly associated with it, e.g., high serum parathyroid hormone, increases risk for fatal prostate cancer. Our finding of a > 2.5- fold increased risk for men in the highest tertile of serum calcium is comparable in magnitude to the risk associated with family history and could add significantly to our ability to identify men at increased risk for fatal prostate cancer.