Epidemiological data provide a strong correlation between the prevalence of certain cancers and exposure to sunlight, consis­tent with chemopreventive effects of 1,25(OH)2D3, particularly in breast, prostate and colon cancers. No epidemiologic studies have directly measured vitamin D concentrations or in­take on total cancer incidence or mortality. However, higher rates of total cancer mortality in regions with less average UV- B radiation exposure, among African-Americans, and among overweight and obese people, each associated with lower cir­culating vitamin D, and a greater cancer mortality when individ­uals are diagnosed in the months when vitamin D levels are lowest are compatible with a benefit of vitamin D on cancer mortality.

The vitamin D hypothesis may apply to multiple cancer sites, but the research focus has been primarily on colorectal, prostate, and breast cancers. Besides the inverse correlation with cancer mortality with average regional UV-B radiation, study for the other sites has been essentially non-existent or sporadic, and thus little can be said.

a) Breast cancer

An inverse association between regional sunlight exposure and breast cancer mortality has been observed in several analyses. However, an analysis within the Nurses’ Health Study did not find the expected geographic gradient for breast cancer in­cidence.

One nested case-control study based on 96 breast cancer cas­es found no association between prediagnostic 1,25(OH)2D3 concentration and risk of breast cancer; circulating 25(OH)D3 was not examined.

John et al. analysed data from NHANES I based on 190 women with incident breast cancer from a cohort of 5009 women. Several measures of sunlight exposure and dietary vit­amin D intake were associated with a moderate reduction in breast cancer risk. In the Nurses’ Health Study, vitamin D in­take was examined prospectively in relation to breast cancer risk based on 3482 incident cases of breast cancer. Total vitamin D intake (dietary plus supplements) was associated with a lower risk of breast cancer (RR=0.72; 95% CI=0.55- 0.94); similar inverse associations were observed with other components of diary foods (lactose, calcium) so it was difficult to conclude definitively an independent effect of vitamin D. However, total vitamin D intake was more strongly associated with lower risk than was dietary or supplemental vitamin D in­take individually, which is suggestive of an independent effect of vitamin D. Thus, the data for breast cancer incidence are suggestive of a benefit from vitamin D, but overall data are rel­atively sparse and inconclusive.

b)  Colorectal cancer

The epidemiologic evidence that high vitamin D status may contribute to lower rates of colorectal cancer is strong and con­sistent. The data linking average regional UV-B radiation and cancer mortality rates appear to suggest a stronger asso­ciation for colorectal cancer than for other cancer sites. About 7000 premature deaths from colorectal cancer annually in the US due to inadequate doses of UV-B radiation were esti­mated. This estimate for colorectal cancer would account for about 30% of the total premature cancer deaths due to low UV- B whereas colorectal cancer mortality accounts for only about 10% of the total deaths from cancer.

Studies that have examined circulating 25(OH)D3 levels and subsequent risk of colorectal cancer or adenoma, the cancer precursor, have found a lower risk associated with higher 25(OH)D3 concentrations, with one exception. In the Washington County, Maryland cohort, an inverse relation between circulating 25(OH)D3 was observed in the first eight years after the blood sample collection, but no associa-

tion was observed in cases diagnosed 10-17 years after the sample collection. A study conducted in Finland found no relation between serum 1,25(OH)2D3 concentration and col­orectal cancer incidence, but an inverse relation was suggest­ed for 25(OH)D3 level, particularly for rectal cancer (48). A re­cent analysis in the Nurses’ Health Study found a significant inverse association between 25(OH)D3 and colorectal cancer risk . Several studies that have examined circulat­ing vitamin D levels and risk of colorectal adenoma, cancer precursor, suggest an inverse association with 25(OH)D3 and possibly 1,25(OH)2D3, particularly for advanced adenomas. In regards to the required 25(OH)D3 level to reduce opti­mally colorectal cancer risk, no threshold was suggested in any of the studies. In the Nurses’ Health Study, the largest rel­evant study of colorectal cancer, based on 193 incident cases, the RR decreased across quintiles, with a RR of 0.53 (CI, 0.27-1.04) for quintile 5 versus 1. The median 25(OH)D3 con­centration in quintile 5 was 88 nmol/L. When the relationships between colorectal cancer and dietary or supplementary vita­min D have been investigated in cohort studies of men and women or both sexes, and in case- control studies, the majority of studies suggested in­verse associations for colon or rectal cancer, or both. Get the medication you need. Buy cialis professional

All the studies of colorectal cancer that took into account sup­plementary vitamin D reported an inverse association. In these studies, the cutpoint for the top category was from approxi­mately 500 to 600 IU/day, with an average of approximately 700-800 IU/day in this category. The risk reduction in the top versus bottom category was as follows: 46%, 34%, 58%, 24%, 30%, 29% male, 0% female, and 50% males, 40% females.

c) Prostate cancer

For prostate cancer, the results regarding vitamin D are gen­erally non-supportive. In populations where severe vitamin D deficiency is uncommon, higher 25(OH)D3 level has not been associated with a reduced risk. Only two studies, which were conducted in Nordic countries, supported an inverse association for 25(OH)D3, though one of these studies also found an increased risk in men with the highest 25(OH)D3 values (76). Because of the high latitude and reduced sun­shine exposure in Nordic countries, 25(OH)D3 levels were quite low, and 1,25(OH)2D3 synthesis is impaired only when 25(OH)D3 is seriously deficient (77-80). Thus, it is possible that the 25(OH)D3 levels were low enough to influence sub­strate availability for 1,25(OH)2D3, though 1,25(OH)2D3 was not measured in these studies. Regarding 1,25(OH)2D3, one study (70) is supportive, while another is suggestive (71) for an inverse association for circulating 1,25(OH)2D3 and aggres­sive prostate cancer, particularly in older men. In a case-con­trol study conducted in the UK, where vitamin D deficiency is relatively common in the elderly, regular foreign holidays, higher sunbathing score, and higher exposure to UV radiation were associated with a reduced risk of prostate cancer (82). A recent nested case-control study did not support a reduced risk of prostate cancer associated with higher 1,25(OH)2D3 or 25(OH)D3, but the vast majority of cancers was organ- confined and detected through PSA elevation in this study. Another recent small study based on 83 cases from the Na­tional Prevention of Cancer Trial found no association be­tween plasma 25(OH)D3 or 1,25(OH)2D3 and total prostate cancer risk. In contrast to colorectal cancer, none of the four studies that have evaluated whether dietary or supple­mental vitamin D is related to risk of prostate cancer support a protective association. In one cohort, vitamin D intake was found to be inversely associated with colorectal cancer risk, but not with prostate cancer risk. This finding suggests the effect of dietary vitamin D may differ between prostate and colorectal cancer.