Abstract ED07-02: Ecological and other studies supporting a role of Vitamin D in reducing the risk of cancer and increasing survival with cancer
Authors: Grant William 
Published: May 2012

Abstract
ED07-02
The ecological approach was used in developing the solar ultraviolet-B (UVB)/vitamin D/cancer hypothesis based on the geographical variation of colon cancer mortality rates in the United States [Garland and Garland, 1980]. Since then, the ecological approach has identified over 15 types of cancer for which UVB and vitamin D seem to reduce risk [Grant and Garland, 2006; Boscoe and Schymura, 2006]. The reasons that the ecological approach is an appropriate method to investigate the role of solar UVB and vitamin D in modifying the risk of cancer include: solar UVB is the most important source of vitamin D for most people, and provides about 1000 IU/day in summer in the United States via casual irradiance; 1000-1500 IU/day, raising serum 25-hydroxyvitamin D levels by 10-15 ng/mL to 30-40 ng/mL, gives significant protection against many types of cancer; vitamin D seems to be effective in reducing the risk of cancer at the latter stages, perhaps by reducing angiogenesis and metastasis; other important risk-modifying factors can be included in such studies; and there are many data sets and populations that can be included in ecological studies. Ecological studies have proven to be very powerful in identifying and quantifying risk-modifying factors for both chronic and infectious diseases; earlier concerns were largely based on the difficulty in finding support for the link between animal fat and cancer risk found in multi-country studies. Recently it was realized that many of the observational studies were conducted on older people and that the role of diet occurs early in life, so younger people should be studied.
The cancer mortality rates in the United States for two periods, 1950-69 and 1970-94 [Devesa et al., 1999] have been very useful in ecological studies to determine the role of various cancer risk-modifying factors. In the study by Grant and Garland [2006], a number of risk-modifying factors were used in addition to solar UVB for July 1992 [Leffell and Brash, 1996] including smoking, alcohol consumption, Hispanic heritage, poverty level, and urban/rural residence. More recent studies included indices for dietary iron and zinc [Grant, 2008a] and an index for air pollution, acid rain in 1985 [Grant, in press]. For those who question whether solar UVB dose is a reliable index of vitamin D production, it is also possible to use incidence of or death from non-melanoma skin cancer, which is largely related to integrated lifetime UVB irradiance. This index was used in an ecological study of cancer mortality rates in Spain [Grant, 2007], as well as cancer incidence in sunny countries [Tuohimaa et al., 2007].
The cancers with large significant inverse correlations with UVB indices in Grant and Garland [2006], Grant [2007, 2008a], and Grant [in press] are breast, colon, esophageal, gallbladder, gastric, ovarian, and rectal cancer, Hodgkin’s lymphoma and non-Hodgkin’s lymphoma (NHL). Renal and uterine corpus cancers were found inversely correlated with UVB in the United States but not in Spain.
Prostate cancer mortality rates have a different geographical variation in the United States than those twelve types of cancer. Prostate cancer has high mortality rates in the northern states and low rates in the southern states. I hypothesized that the geographic variation of prostate cancer mortality rates in the United States is related to a viral infection more common in winter, and that higher serum 25(OH)D levels in winter reduce the risk of such infections [Grant, 2008b].
Thus, there are eleven types of cancer for which a significant inverse correlation with solar UVB for July was found consistently in ecologic studies of cancer mortality rates in the United States for the period 1970-94 and one for which the UVB index is latitude.
There are three types of cancer with inconsistent results with respect to vitamin D: bladder, lung and pancreatic cancer. Bladder cancer had a marginally insignificant inverse correlation with UVB in the air pollution study, and smoking is an important risk factor for bladder cancer. Lung cancer is strongly linked to smoking, but there is evidence that vitamin D reduces risk [Giovannucci et al., 2006]. Pancreatic cancer was directly correlated with latitude in Spain as well as in Japan [Kinoshita et al., 2007].
Observational studies have also supported the role of vitamin D in reducing the risk of cancer. In the Health Professionals Follow-Up Study, a vitamin D index based on oral intake and production of vitamin D was significantly inversely correlated with five types of cancer: colorectal, esophageal, pancreatic and oral/pharyngeal cancer and leukemia, and insignificantly with six other types: bladder, gastric, lung, prostate (advanced) and renal cancer and NHL [Giovannucci et al., 2006].
Vitamin D has also been associated with increased survival for those with cancer. The most extensive work in this regard has been done in Norway. Based on cancer registry data, it was determined that those diagnosed with breast, colon, or prostate cancer and Hodgkin lymphoma in summer or fall had 15-25% higher 36-month survival rates than those diagnosed in winter or spring [Porojnicu et al., 2008]. Serum 25-hydroxyvitamin D levels in Norway increase from 21 ng/mL in winter to 30 ng/mL in summer [Moan et al., 2005].
While the ecological and observational studies largely support the roles of UVB and vitamin D in reducing the risk of many types of cancer, properly-designed and conducted randomized controlled trials (RCTs) are generally required to fully establish the beneficial role of vitamin D. Unfortunately, many of the vitamin D supplementation trials used only 400 IU/day [Grant and Garland, 2004], a value too low to produce a significant effect. There is one RCT with post-menopausal women that used 1100 IU/day vitamin D plus calcium. A 35% reduction in all-cancer incidence rate was found for vitamin D between the ends of the first and fourth years [Lappe et al., 2007].
There are many health benefits of vitamin D [Holick, 2007]. Thus, while the evidence to date on vitamin D and cancer risk reduction is strongly supportive but not conclusive, it seems worthwhile to suggest that all those with or at risk of cancer have serum calcidiol levels above 40 ng/mL.
Disclosure
I receive funding from the UV Foundation (McLean, VA).
Citation Information: Cancer Prev Res 2008;1(7 Suppl):ED07-02.