Vitamin D levels and cancer incidence in 217,244 individuals from primary health care in Denmark

Abstract

Vitamin D has been linked to cancer development in both pre‐clinical and epidemiological studies. Our study examines the association between serum levels of vitamin D and cancer incidence in the Capital Region of Denmark. Individuals who had vitamin D analyzed at The Copenhagen General Practitioners Laboratory between April 2004 and January 2010 were linked to Danish registries with end of follow‐up date at Dec 31st 2014, excluding individuals with pre‐existing cancer. Cox regression models adjusted for age in one‐year intervals, sex, month of sampling, and Charlson Comorbidity Index were applied. The study population of 217,244 individuals had a median vitamin D level of 46 nmol/L (IQR 27–67 nmol/L). Non‐melanoma skin cancer was the most frequent form of cancer, followed by breast‐, lung‐, and prostate cancers. No associations were found between increments of 10 nmol/L vitamin D and incidence of breast, colorectal, urinary, ovary or corpus uteri cancer. However, higher levels of vitamin D were associated with higher incidence of non‐melanoma (HR 1.09 [1.09–1.1]) and melanoma skin cancer (HR 1.1 [1.08–1.13]) as well as prostate (HR 1.05 [1.03–1.07]) and hematological cancers (HR 1.03 [1.01–1.06]), but with lower incidence of lung cancer (HR 0.95 [0.93–0.97]). In our study, vitamin D levels are not associated with the incidence of several major cancer types, but higher levels are significantly associated with a higher incidence of skin, prostate, and hematological cancers as well as a lower incidence of lung cancer. These results do not support an overall protective effect against cancer by vitamin D.

25-Hydroxyvitamin D status, vitamin D intake, and skin cancer risk: a systematic review and dose–response meta-analysis of prospective studies

“…a P-value for heterogeneity among the studies within each cancer type. www.nature.com/scientificreports/ skin cancer, with the hazard ratio seemed to peak around a vitamin D status of 80 nmol/L in the non-linear trend analysis 33 . Because of the limited number of studies included in our non-linear dose-response meta-analyses, mainly due to the missing information on the range of vitamin D levels, further studies should aim to clarify the shape of the dose-response relationship.…”

“…Thirteen cohort studies [24][25][26]28,29,[31][32][33][34]43,[51][52][53] were eligible for inclusion. Of these, ten studies were included in the metaanalysis of 25(OH)D level and skin cancer [24][25][26]28,29,[31][32][33]51,53 and four studies were included in the meta-analysis of vitamin D intakes from diet and supplement and skin cancer risk 32,34,43,52 (Table S1 and S2). Seven studies were from North America 24,26,28,29,32,34,43 , five from Europe 31,33,[51][52][53] , and one from Australia 25 .…”

“…Of these, ten studies were included in the meta-analysis of 25(OH)D level and skin cancer 24 – 26 , 28 , 29 , 31 – 33 , 51 , 53 and four studies were included in the meta-analysis of vitamin D intakes from diet and supplement and skin cancer risk 32 , 34 , 43 , 52 (Table S1 and S2 ). Seven studies were from North America 24 , 26 , 28 , 29 , 32 , 34 , 43 , five from Europe 31 , 33 , 51 – 53 , and one from Australia 25 . Eight studies were rated with moderate risk of bias 24 , 25 , 28 , 32 , 34 , 43 , 51 , 53 and five with serious risk of bias 26 , 29 , 31 , 33 , 52 (Table S3 ).…”

Association between Polymorphisms of Vitamin D Receptor and Lung Cancer Susceptibility: Evidence from an Updated Meta-analysis

“…[35] The most active metabolite form of vitamin D is 1,25-D3, which not only participates in maintaining calcium homeostasis, but also has some non-endocrine effects such as influencing cardiovascular disease, diabetes and cancers. [36,37] Previous studies have proved that high circulating levels of 1,25-D3 have the ability to prevent the development of cancer. [38] Expression and nuclear activation of the VDR are necessary for the function of vitamin D. Thus, genetic alternation of the VDR gene could lead to important defects in gene activation, which is bound to affect the biological effects of vitamin D. At present, a lot of studies have investigated the association between VDR polymorphism and LC susceptibility, but the specific correlation of them still unclear.…”

Vitamin D and Ovarian Cancer: Systematic Review of the Literature with a Focus on Molecular Mechanisms

“…A meta-analysis of four cohort studies reported a possible inverse association of ovarian cancer incidence and circulating 25(OH)D levels that did not reach statistical significance [18]. Mixed results were obtained in more recent ecologic studies [19,20], case-control [21], and cohort studies [22,23] as well. A Mendelian randomization study found that European women with genetically lowered 25(OH)D concentrations due to single nucleotide polymorphisms (SNPs) had higher susceptibility for ovarian cancer [3].…”