25-hydroxyvitamin-d-2 and Colorectal-Neoplasms

Vitamin D deficiency has been associated with several common diseases, including cancer and is being investigated as a possible risk factor for these conditions. We reported the striking prevalence of vitamin D deficiency in Scotland. Previous epidemiological studies have reported an association between low dietary vitamin D and colorectal cancer (CRC). Using a case-control study design, we tested the association between plasma 25-hydroxy-vitamin D (25-OHD) and CRC (2,001 cases, 2,237 controls). To determine whether plasma 25-OHD levels are causally linked to CRC risk, we applied the control function instrumental variable (IV) method of the mendelian randomization (MR) approach using four single nucleotide polymorphisms (rs2282679, rs12785878, rs10741657, rs6013897) previously shown to be associated with plasma 25-OHD. Low plasma 25-OHD levels were associated with CRC risk in the crude model (odds ratio (OR): 0.76, 95% Confidence Interval (CI): 0.71, 0.81, p: 1.4×10(-14)) and after adjusting for age, sex and other confounding factors. Using an allele score that combined all four SNPs as the IV, the estimated causal effect was OR 1.16 (95% CI 0.60, 2.23), whilst it was 0.94 (95% CI 0.46, 1.91) and 0.93 (0.53, 1.63) when using an upstream (rs12785878, rs10741657) and a downstream allele score (rs2282679, rs6013897), respectively. 25-OHD levels were inversely associated with CRC risk, in agreement with recent meta-analyses. The fact that this finding was not replicated when the MR approach was employed might be due to weak instruments, giving low power to demonstrate an effect (<0.35). The prevalence and degree of vitamin D deficiency amongst individuals living in northerly latitudes is of considerable importance because of its relationship to disease. To elucidate the effect of vitamin D on CRC cancer risk, additional large studies of vitamin D and CRC risk are required and/or the application of alternative methods that are less sensitive to weak instrument restrictions.

Topics: 25-Hydroxyvitamin D 2; Adult; Aged; Case-Control Studies; Chromatography, Liquid; Colorectal Neoplasms; Female; Genotype; Humans; Likelihood Functions; Male; Mendelian Randomization Analysis; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; Risk Factors; Scotland; Tandem Mass Spectrometry; Vitamin D Deficiency

Low levels of vitamin D and excess body weight are both factors associated with increased risk of cancer. The increased risk seems to be proportional to the increase in BMI, and to decrease in serum 25-hydroxyvitamin D (25(OH)D) level. Our earlier investigations suggest that serum 25(OH)D levels decrease with increasing BMI. Although the connection between cancer risk, BMI and vitamin D status might be arbitrary, it has not been discussed in the literature so far. In this study, we analyze data published in current meta-analysis, prospective studies, and systematic reviews on cancer-specific risk attributed to high BMI and low vitamin D status. The contribution of low 25(OH)D levels associated with high BMI to increased cancer risk was calculated for 13 vitamin-D-sensitive cancers with a focus on colorectal and breast cancer as the most frequently studied vitamin-D-sensitive cancer types. Our study suggests that a low vitamin D status may explain at least 20% of the cancer risk attributable to high BMI. The contribution of low 25(OH)D to the increased cancer risk with increasing BMI may be different for different cancer types. Thus, we find 40% for breast cancer, and 26 and 75% for colorectal cancer in men and women, respectively.

Topics: 25-Hydroxyvitamin D 2; Adult; Body Mass Index; Breast Neoplasms; Calcifediol; Colorectal Neoplasms; Female; Humans; Male; Middle Aged; Neoplasms; Obesity; Prevalence; Risk Factors; Sex Factors; Vitamin D Deficiency; Young Adult