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.
Highlights
Global differences in incidence are primarily driven by its main risk factors tobacco and alcohol exposure[2,3], but over the last decade infection by human papillomavirus has emerged as an important cause of head and neck cancer (HNC) subsites, in particular oropharynx cancer[4]
Visual inspection suggests clear differences in circulating 25(OH)D3 that are consistent with sun exposure being the most important determinant of circulating vitamin D, 25(OH)D3 concentrations were lowest among those who had their blood drawn around February and March and highest among those who had their blood drawn around August
For those deceased with HNC indicated as underlying cause of death (87 deaths), HRlog[2] was 0.68 and adjusting the cause-specific mortality analysis for potential confounders did not affect the hazard ratios (HR) estimates notably (HRlog2 0.71, 9% higher 25(OH)D3 concentrations (95% confidence interval (CI)) 0.53–0.96, Ptrend = 0.02)
Summary
About 650,000 new cases of head and neck cancer (HNC) and 450,000 new cases of esophageal cancer occur worldwide each year[1]. In contrast to mechanistic studies, epidemiological studies of circulating 25(OH)D have not provided consistent evidence supporting a beneficial role of vitamin D in terms of cancer incidence, the exception being colorectal cancer for which the majority of studies support an inverse association between circulating vitamin D and risk[9,10]. While reverse causality is a principal concern in retrospective studies, the current study aimed to provide a comprehensive evaluation of pre-diagnostic circulating 25(OH)D and risk of cancers of the head and neck and oesophagus from a large case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). We aimed to evaluate if pre-diagnostic circulating 25(OH)D is associated with survival following cancer diagnosis
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