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Lower cancer risk in people with higher vitamin D levels

Higher vitamin D concentration associated with lower risk of incident total cancer in Japan

Louise Prime

Thursday, 08 March 2018

Men and women with higher circulating vitamin D concentrations had a lower risk of subsequently developing cancer, including liver cancer, research from Japan has shown. The authors of the study*, published today by the BMJ, said their findings support the hypothesis that vitamin D has protective effects against cancers at many sites.

Because it is a precursor to a potent bioactive compound (1,25-dihydroxyvitamin D) that has diverse antineoplastic properties, vitamin D has been previously hypothesised to confer protection against cancer; and in vitro, animal and some epidemiological studies have supported this theory.

A research team from Tokyo designed a large, nested case-cohort study to evaluate the association between pre-diagnostic circulating vitamin D concentration and the subsequent risk of overall and site-specific cancer, using data from the ongoing Japan Public Health Centre-based Prospective Study cohort.

This study had, at baseline, asked all 140,420 participants to answer self-administered questionnaires including questions on demographic characteristics, medical history, and lifestyle-related factors. Of these, 113,461 (81%) also completed a validated food frequency questionnaire, and 49,011 also voluntarily donated 10ml of venous blood during their health check-ups. Mean follow-up was 16 years.

Among the 33,736 study participants who had both responded to the baseline questionnaire and provided adequate blood samples, and had no history of cancer at baseline, the researchers found 3,301 incident cases of cancer, and randomly selected a control group of 4,044 sub-cohort participants.

They divided participants into quarters according to baseline plasma concentration of 25-hydroxyvitamin D, measured by enzyme immunoassay, based on the sex- and season-specific distribution of 25-hydroxyvitamin D among sub-cohorts. They then used weighted Cox proportional hazard models to compare the incidence of overall or site-specific cancer across categories of 25-hydroxyvitamin D concentration, using the lowest quarter as the reference.

The researchers reported a significant inverse association between plasma 25-hydroxyvitamin D concentration and the risk of total cancer, with multivariable adjusted hazard ratios (HR) for the second to fourth quarters compared with the lowest quarter of 0.81, 0.75, and 0.78 respectively. They also reported an inverse association for liver cancer, although this was only statistically significant when comparing the highest with the lowest quarters (HR 0.45).

The study authors observed a potential ceiling effect, and noted that, considering the results of earlier trials, “This may also suggest that raising a low 25-hydroxyvitamin D concentration to an intermediate concentration may provide protection, whereas raising it to a higher concentration (probably above around 80nmol/l) may provide no further benefit."

They concluded: “In this large prospective study, higher vitamin D concentration was associated with lower risk of total cancer. These findings support the hypothesis that vitamin D has protective effects against cancers at many sites."


*Budhathoki S, Hidaka A, Yamaji T, et al. Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: large case-cohort study within Japan Public Health Center-based Prospective Study cohort. BMJ 2018;360:k671. http://dx.doi.org/10.1136/bmj.k671

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