Malignancy Risk & Vitamin D Deficiency: An Unclear Relationship

Several recent studies attempted to determine the role of vitamin D supplementation in oncogenesis and cancer treatment. The relationship, however, remains unclear.

A study in the Journal of Clinical Oncology showed, for example, that a deficiency of serum 25-hydroxyvitamin D (25-OH D) increased the odds of adverse prostate cancer pathology among men with localized prostate cancer undergoing radical prostatectomy.¹ Serum 25-OH D levels less than 30 ng/mL were associated with more than twice the risk of adverse pathology.

A systematic review of 7 studies of vitamin D and bladder cancer showed that vitamin D deficiency increased the risk of developing the disease (this was found in 5 of the 7 studies).² Higher levels of vitamin D correlated with better survival and outcomes.

A pooled analysis published in PLoS One showed that 25 OH D concentrations of 40 ng/mL or greater were associated with a substantial risk reduction of all invasive cancers.³ The analysis used data from 2 cohorts including more than 2300 people with multiple cancer types. Women with concentrations of 40 ng/mL or greater had a 67% lower risk for cancer than women with concentrations less than 20 ng/mL.

Other studies have evaluated the role of vitamin D after a cancer diagnosis. JAMA Oncology recently published the results of a cohort study of 1666 women with breast cancer measuring the level of vitamin D in the blood at the time of breast cancer diagnosis.⁴ 

Higher serum 25-OH D levels were independently associated with better outcomes for patients, including longer overall survival. Compared with the lowest tertile of vitamin D levels, those women with the highest levels had a superior overall survival; this advantage was even greater among premenopausal women.

A study published in JAMA Oncology showed, interestingly, that the benefits of vitamin D₃ supplementation for the prevention of advanced colorectal adenomas may vary according to vitamin D receptor genotype.⁵ The study of about 1700 people showed that the effect of vitamin D₃ supplementation on advanced adenomas varied according to genotype at 2 vitamin D receptor SNPs: supplementation reduced risk among patients with rs7968585 with the AA genotype, though it increased risk among patients with 1 or 2 G alleles.

The researchers said that these results are a “first step” toward identifying which individuals may benefit or be harmed by vitamin D interventions, reflecting the variety of results from studies of supplementation in recent years.

According to the National Cancer Institute, there are not enough available data to establish whether taking vitamin D can prevent cancer.⁶ New randomized trials will need to be conducted to more fully understand the effect of vitamin D on cancer and its outcomes.

Among those studies in progress are the Vitamin D/Calcium Polyp Prevention Study (ClinicalTrials.gov Identifier: NCT00153816), which is examining whether vitamin D supplementation given alone or with calcium prevents the development of colorectal adenomas in patients with previous adenoma removal, and the VITAL trial (ClinicalTrials.gov Identifier: NCT01169259), which is evaluating whether vitamin D supplements can prevent a variety of cancers in older men and women. 

References

1. Nyame YA, Murphy AB, Bowen DK, et al. Associations between serum vitamin D and adverse pathology in men undergoing radical prostatectomy. J Clin Oncol. 2016;34(12):1345-9.
2. Low vitamin D levels linked to increased risk of bladder cancer. University of Warwick website. http://www2.warwick.ac.uk/newsandevents/news/low_vitamin_d/. Published November 8, 2016. Accessed December 19, 2016.
3. McDonnell SL, Baggerly C, French CB, et al. Serum 25-hydroxyvitamin D concentrations >=40 ng/mL associated with a >65% lower cancer risk: pooled analysis of randomized trial and prospective cohort study. PLoS One. 2016;11(4):e0152441.
4. Yao S, Kwan ML, Ergas IJ, et al. Association of serum level of vitamin D at diagnosis with breast cancer survival: a case-cohort analysis in the pathways study. JAMA Oncol. 2016 Nov 10. doi: 10.1001/jamaoncol.2016.4188 [Epub ahead of print]
5. Barry EL, Peacock JL, Rees JR, et al. Vitamin D receptor genotype, vitamin D3 supplementation, and risk of colorectal adenomas: a randomized clinical trial. JAMA Oncol. 2016 Dec 15. doi: 10.1001/jamaoncol.2016.5917 [Epub ahead of print]
6. Chung M, Lee J, Terasawa T, Lau J, Trikalinos TA. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med. 2011;155(12):827-38.

This article originally appeared on Cancer Therapy Advisor