Abstract
Purpose
Epidemiological studies suggest that low levels of vitamin D (25OHD) constitute a risk factor for more aggressive prostate cancer. We examined the relationship between pre-diagnostic serum levels of vitamin D, parathyroid hormone (PTH), and calcium and risk of prostate cancer according to tumor aggressiveness.
Methods
We performed a nested case–control study within the Malmö Diet and Cancer Study on 943 incident prostate cancer cases. Tumor aggressiveness was defined by Gleason score, TNM stage, and serum levels of total prostate-specific antigen. Odds ratios (OR) were calculated for different quartiles of serum levels of 25OHD, PTH, and calcium, and for interactions between them.
Results
We found no significant association when comparing aggressive to non-aggressive disease regarding vitamin D, PTH, or calcium. There was a trend toward an increased risk in low-grade tumors, i.e., Gleason score ≤6, and a significant association regarding Gleason score 7 tumors with OR 1.70 (1.09–2.65) in the highest quartile of vitamin D. Stratifying the analysis yielded several significant findings demonstrating a nonspecific interaction between the metabolites. In men with PTH above median, the risk of aggressive prostate cancer was double in the highest vitamin D quartile, OR 2.01 (1.24–3.25), and for non-aggressive cancer 1.82 (1.25–2.66). There was an inverse effect on risk of prostate cancer in men with PTH above median and vitamin D ≤50 nmol/L, OR 0.25 (0.09–0.71) and calcium ≤2.37 mmol/L, OR 0.53 (0.34–0.82) for aggressive cancer.
Conclusions
This study showed no significant association when comparing aggressive to non-aggressive disease. There was a possible relationship between vitamin D and low-risk tumors. There were both positive and negative interactions between PTH, calcium, and vitamin D and risk of prostate cancer. These results were similar for low-risk and aggressive cases.
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Acknowledgments
This work was supported by grants from the Swedish Research Council (K2007-69X-20487-01-3), the Ernhold Lundström Foundation, the Einar and Inga Nilsson Foundation, Malmö University Hospital Cancer Research Fund, Malmö University Hospital Funds and Donations, the Crafoord Foundation, Region Skåne, the Mossfelt Foundation, Fundacion Federico S.A, the Swedish Cancer Society (CAN 2006/1554), and the Gunnar Nilsson Cancer Foundation.
Authors’ contribution
JB participated in the design of the study, collected some of the data, performed the statistical analysis, and drafted the manuscript. MA participated in the design of the study and helped to draft the manuscript. Jonas M participated in the design of the study and helped to draft the manuscript. DU collected the majority of the data. Johan M participated in the design of the study and helped to draft the manuscript. All authors read and approved the final manuscript.
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Brändstedt, J., Almquist, M., Ulmert, D. et al. Vitamin D, PTH, and calcium and tumor aggressiveness in prostate cancer: a prospective nested case–control study. Cancer Causes Control 27, 69–80 (2016). https://doi.org/10.1007/s10552-015-0684-3
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DOI: https://doi.org/10.1007/s10552-015-0684-3