Evidence supporting the role of vitamin D in reducing the risk of cancer

Comments on `Prospects for chemoprevention of cancer' by R. M. Tamini et al., J Intern Med 2002; 251: 286–300. The recent paper by Tamini et al. [1] concluded that the overall evidence for a chemopreventive role for vitamin D against cancer remains insufficient. This conclusion is at odds with the growing body of literature supporting the role of vitamin D from diet and through the action of solar ultraviolet B (UV-B) radiation (280–320 nm) on 7-dehydrocholesterol in the skin in reducing the risk of cancer incidence and mortality. The evidence in support of this hypothesis is outlined here. First, there are a number of epidemiological studies on the links between solar UV-B radiation and/or vitamin D and cancer incidence and/or mortality rates. A 19-year prospective study found that men who consumed 150+ IU day–1 of vitamin D3 had half the risk of colorectal cancer as those who consumed less [2]. A nested case–control study found that individuals with 30+ ng mL–1 of 25-hydroxyvitamin D3 [25-(OH)2D3] in serum had half the risk of colorectal cancer as those with lower levels [3]. Similar findings were reported in another major study where the relative risk of large bowel cancer decreased with increasing level of serum 25-(OH)2D3 [4]. Women with high levels of 1,25-(OH)2D3 in serum had only one-fifth the risk of breast cancer as those with low levels [the relative risk was 5.2 (95% CI=2.1–12.8) for lowest versus highest quartile of serum 1,25-(OH)2D3] [5]. Women in the Nurses' Health Study Cohort who had consistently high total vitamin D3 intakes had markedly lower risk of colorectal cancer (relative risk=0.42 (95% CI=0.19–0.91)) [6]. Women in the National Health Survey who had a high intake of vitamin D3 from supplements, or had dermatological evidence of high lifetime sun (actinic) exposure had a significantly lower risk of breast cancer [7]. One recent paper reported a strong protective role for solar UV-B exposure against prostate cancer [8]. Another reported a protective role for occupational and residential UV-B exposure for cancers of the breast, colon and ovaries [9]. A recent ecological study found solar UV-B radiation to be protective against a dozen types of cancer [10]. Solar UV-B doses for July were obtained from the Total Ozone Mapping Spectrometer. It was estimated that the annual average mortality as a result of cancer from 1970 to 1994 in the US because of insufficient UV-B radiation (or vitamin D) was approximately 23 600 deaths. It has also been estimated that approximately 25% of breast cancer mortality rates in northern Europe can be attributed to insufficient levels of vitamin D [11]. The number of papers listed in PubMed for various dietary agents that are considered likely to have chemopreventive properties also supports an important role for vitamin D. A search of total and recent entries was made for 13 such agents including those considered in Ref. [1], along with the word `cancer'. Vitamin D ranks fourth between 1 January 2001 and 15 May 2002 with 327 entries after antioxidants (1429 entries), retinoids (1193) and vitamin E (331). The hypothesis that vitamin D reduces the risk of cancer is supported by numerous epidemiological and laboratory studies, and is generating major new research initiatives. The mechanisms by which 25-(OH)2D3 and 1,25-(OH)2D3 and their analogues exert their growth-inhibitory effects include effects on angiogenesis, apoptosis, cell differentiation, cell cycle regulation and metastases [12]. Interest in vitamin D analogues for cancer prevention or therapy is so high that nearly 400 structural analogues of vitamin D3 have been synthesized and evaluated for their efficacy in cancer chemoprevention [13]. The benefits of solar UV-B exposure and vitamin D3 supplementation in reducing the risk of cancer should be acknowledged by the public health community and translated into guidelines that will lead to reduced risk of cancer incidence and mortality.