Serum 25-hydroxyvitamin D levels predict cancer survival: a prospective cohort with measurements prior to and at the time of cancer diagnosis
Received 1 March 2019
Accepted for publication 17 May 2019
Published 8 August 2019 Volume 2019:11 Pages 695—705
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 2
Editor who approved publication: Professor Henrik Toft Sørensen
Trude Eid Robsahm,1 Steinar Tretli,1 Peter Abusdal Torjesen,2 Ronnie Babigumira,1 Gary G Schwartz3
1The Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway; 2The Hormone Laboratory, Department of Endocrinology, Oslo University Hospital Health Authority, Oslo, Norway; 3Department of Population Health, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USA
Purpose: Circulating 25-hydroxyvitamin D (25-OHD) levels have been inversely associated with cancer death, but the nature of this relationship is unclear. We investigated this association using repeated measurements of serum 25-OHD.
Patients and methods: Pre-diagnostic serum samples were collected in population health surveys in Norway (1973–2004). Participants who subsequently developed cancer (1984–2004) provided a second serum sample at the time of cancer diagnosis. Samples were stored in the Janus Serum Bank. Repeated samples existed from 202 breast cancers, 193 lung cancers, 124 lymphomas, and 37 colon cancers. Serum 25-OHD was measured via competitive radioimmunoassay. Cox regression models assessed associations between 25-OHD and cancer-specific death (case fatality) through 2012, given as hazard ratios (HRs) with 95% confidence intervals (CIs).
Results: The median time between pre-diagnostic and diagnostic samples was 14.4 years. The median 25-OHD levels were 63.3 and 62.5 nmol/L, respectively. During follow-up, 313 cancer deaths occurred. Compared to low pre-diagnostic 25-OHD levels (<46 nmol/L), higher levels (≥46 nmol/L) had significantly lower HRs (39–54%) of case fatality. This result was also seen for the diagnostic samples. Donors who had both samples at high (≥62 nmol/L) levels had 59% lower HR of case fatality, compared to those for whom both samples were at low levels (<46 nmol/L). Furthermore, versus a decline in serum 25-OHD (median −22.4 nmol/L) from pre-diagnostic to diagnostic samples, a rise (median 22.3 nmol/L) was associated with lower case fatality (HR 0.57, 95% CI 0.43−0.75).
Conclusion: Our findings suggest a causal relationship between vitamin D and cancer case fatality.
Keywords: serum 25-OHD, repeated measurement, longitudinally, cancer case fatality
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