Prediagnostic Circulating Parathyroid Hormone Concentration and Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition Cohort

Abstract
Background: Parathyroid hormone (PTH) has been proposed to play a promoting role in carcinogenesis. However, no epidemiologic studies have yet directly investigated its role in colorectal cancer (CRC). Methods: A case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort was conducted with 1,214 incident, sporadic CRC cases matched to 1,214 controls. Circulating prediagnostic PTH and 25-hydroxy vitamin D [25(OH)D] concentrations were measured by enzyme-linked immunosorbent assays. Detailed dietary and lifestyle questionnaire data were collected at baseline. Multivariable conditional logistic regression was used to estimate the incidence rate ratio (RR) with 95% confidence intervals (95% CI) for the association between circulating PTH and CRC risk. Results: In multivariate analyses [including adjustment for 25(OH)D concentration] with a priori defined cutoff points, high levels of serum PTH (≥65 ng/L) compared with medium PTH levels of 30–65 ng/L were associated with increased CRC risk (RR = 1.41, 95% CI: 1.03–1.93). In analyses by sex, the CRC risk was 1.77 (95% CI: 1.14–2.75) and 1.15 (95% CI: 0.73–1.84) in men and women, respectively (Pheterogeneity = 0.01). In subgroup analyses by anatomical subsite, the risk for colon cancer was RR = 1.56, 95% CI: 1.03–2.34, and for rectal cancer RR = 1.20, 95% CI: 0.72–2.01 (Pheterogeneity = 0.21). Effect modification by various risk factors was examined. Conclusions: The results of this study suggest that high serum PTH levels may be associated with incident, sporadic CRC in Western European populations, and in particular among men. Impact: To our knowledge, this is the first study on PTH and CRC. The role of PTH in carcinogenesis needs to be further investigated. Cancer Epidemiol Biomarkers Prev; 20(5); 767–78. ©2011 AACR.