Circulating vitamin D in relation to cancer incidence and survival of the head and neck and oesophagus in the EPIC cohort

Abstract

Experimental and epidemiological data suggest that vitamin D play a role in pathogenesis and progression of cancer, but prospective data on head and neck cancer (HNC) and oesophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants with blood samples between 1992 and 2000. This analysis includes 497 case-control pairs of the head and neck and oesophagus, as well as 443 additional controls. Circulating 25(OH)D3 were measured in pre-diagnostic samples and evaluated in relation to HNC and oesophagus cancer risk and post-diagnosis all-cause mortality. After controlling for risk factors, a doubling of 25(OH)D3 was associated with 30% lower odds of HNC (OR 0.70, 95% confidence interval [95% CI] 0.56–0.88, Ptrend = 0.001). Subsequent analyses by anatomical sub-site indicated clear inverse associations with risk of larynx and hypopharynx cancer combined (OR 0.55, 95CI% 0.39–0.78) and oral cavity cancer (OR 0.60, 95CI% 0.42–0.87). Low 25(OH)D3 concentrations were also associated with higher risk of death from any cause among HNC cases. No clear association was seen with risk or survival for oesophageal cancer. Study participants with elevated circulating concentrations of 25(OH)D3 had decreased risk of HNC, as well as improved survival following diagnosis.

Assessing the causal association between 25‐hydroxyvitamin D and the risk of oral and oropharyngeal cancer using Mendelian randomization

“…did demonstrate a protective role for 25OHD in ovarian cancer in a well powered MR study. Despite the body of evidence that does not support a protective effect of 25OHD on cancer incidence, there is evidence to support the hypothesis that vitamin D has an effect on cancer progression 8, 11…”

“…Despite the body of evidence that does not support a protective effect of 25OHD on cancer incidence, there is evidence to support the hypothesis that vitamin D has an effect on cancer progression. 8,11 The genetic instrument used in our study specifically proxies average total (free and bound) circulating 25OHD and does not necessarily predict the concentrations of free 25OHD available at the tissues or concentrations of free or bound 1,25OH 2 D in circulation or at the tissue level. Potential anti-cancer effects of vitamin D are via free 1,25OH 2 D interacting with the vitamin D receptor within tissues resulting in reduced angiogenesis, metastasis, cell invasion, inflammation, and proliferation as well as upregulation of apoptosis.…”

“…10 A recent prospective European cohort study also found strong evidence for an inverse association between circulating 25OHD on HNC risk (odds ratio [OR] per doubling of circulating 25OHD concentration 5 0.69 [95% CI: 0.56, 0.87], p 5 9310 24 ). 11 However, Arem et al 12 and Skaaby et al 13 found no convincing evidence of a protective effect of higher 25OHD levels on HNC.…”

“…In an observational study of tobacco‐related tumours, participants with 50% lower circulating 25OHD were more likely to develop HNC after accounting for available potential confounders (Hazard ratio = 1.44 [95% confidence interval (CI): 1.19, 1.73]) 10. A recent prospective European cohort study also found strong evidence for an inverse association between circulating 25OHD on HNC risk (odds ratio [OR] per doubling of circulating 25OHD concentration = 0.69 [95% CI: 0.56, 0.87], p  = 9×10 −4 ) 11. However, Arem et al 12.…”

Vitamin D receptor as a marker of prognosis in oesophageal adenocarcinoma: a prospective cohort study

“…Research into the impact of vitamin D with respect to oesophageal adenocarcinoma risk is highly controversial, with observational studies having reported null results, decreased risks, or indeed increased risks of oesophageal adenocarcinoma in patients with higher levels of vitamin D intake or status [ 21 – 24 ]. No clear associations for circulating vitamin D levels and prognosis after a diagnosis of oesophageal cancer were identified in a European cohort study, although that included only 74 adenocarcinoma patients [ 25 ]. Our study provides some evidence that VDR is associated with oesophageal adenocarcinoma outcomes, and therefore indirect evidence of a biological role for vitamin D.…”