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BMJ. 2018 Mar 7;360:k671. doi: 10.1136/bmj.k671.

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.

Author information

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, 104-0045, Japan.
Department of Medical Statistics, Shiga University of Medical Science, Ohtsu, Shiga, 520-2192, Japan.
Division of Biostatistical Research, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, 104-0045, Japan.
Biostatistics Division, Center for Research Administration and Support, National Cancer Center, Chuo-ku, Tokyo, 104-0045, Japan.
CL New Product Development Department, Fujirebio Inc., Hachioji-shi, Tokyo, 192-0031, Japan.



To evaluate the association between pre-diagnostic circulating vitamin D concentration and the subsequent risk of overall and site specific cancer in a large cohort study.


Nested case-cohort study within the Japan Public Health Center-based Prospective Study cohort.


Nine public health centre areas across Japan.


3301 incident cases of cancer and 4044 randomly selected subcohort participants.


Plasma concentration of 25-hydroxyvitamin D measured by enzyme immunoassay. Participants were divided into quarters based on the sex and season specific distribution of 25-hydroxyvitamin D among subcohorts. Weighted Cox proportional hazard models were used to calculate the multivariable adjusted hazard ratios for overall and site specific cancer across categories of 25-hydroxyvitamin D concentration, with the lowest quarter as the reference.


Incidence of overall or site specific cancer.


Plasma 25-hydroxyvitamin D concentration was inversely associated with the risk of total cancer, with multivariable adjusted hazard ratios for the second to fourth quarters compared with the lowest quarter of 0.81 (95% confidence interval 0.70 to 0.94), 0.75 (0.65 to 0.87), and 0.78 (0.67 to 0.91), respectively (P for trend=0.001). Among the findings for cancers at specific sites, an inverse association was found for liver cancer, with corresponding hazard ratios of 0.70 (0.44 to 1.13), 0.65 (0.40 to 1.06), and 0.45 (0.26 to 0.79) (P for trend=0.006). A sensitivity analysis showed that alternately removing cases of cancer at one specific site from total cancer cases did not substantially change the overall hazard ratios.


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.

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Competing interests: This study was conducted under a collaborative research agreement between the Research Center for Cancer Prevention and Screening, National Cancer Center, Japan, and Fujirebio Inc, Japan, without monetary compensation. Fujirebio Inc, Japan played a major role in the measurement of plasma 25-hydroxyvitamin D, but not in the design, analysis, interpretation, manuscript drafting, or decision to submit the manuscript for publication. All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: no support from any organisation for the submitted work other than those described above; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

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