Vitamin D And The Cancer Connection

The role of vitamin D in cancer prevention perhaps has been known for more than 50 years. Although excessive sun exposure has been documented to increase the risk of skin cancer, research conducted starting as early as 1936 has proved this population of patients with skin cancer to be at a lower risk for other types of cancer. Sun exposure has been correlated with decreased incidence of certain types of cancer such as cancers of the prostate, breast, and colon. Individuals residing in the U.S., which lies in the northern latitudes, have a risk for cancer incidence which is two to three times higher than the risk of cancer incidence of people living in sunnier, equatorial parts of the world.40 This intriguing observation by Apperly40 was followed by several epidemiological studies that demonstrated an inverse relationship between 25-(OH)D3 levels and cancer risk and mortality.41,42

TABLE 5.3

Tissue Distribution of VDR

System

Tissue Type

Cardiovascular

Central nervous system

Connective tissue

Endocrine

Epidermis

Exocrine

Gastrointestinal

Hepatic

Immune

Musculoskeletal

Renal

Reproductive

Cardiac muscle Neurons

Fibroblasts, stroma

Parathyroid gland, thyroid, adrenal, pituitary. Pancreas beta cell Skin, breast, hair follicles Parotid glands, sebaceous gland

Esophagus, stomach, small intestine, large intestine, colon Liver parenchyma

Thymus, bone marrow, B cells, T cells

Bone osteoblasts, osteocytes, cartilage chondrocytes, striated muscle Kidney, urethra

Testis, ovary, placenta, uterus, endometrium, yolk sac, chorioallontroic membrane Lung alveolar cells

Respiratory

Colon Cancer: With respect to colon cancer, there have been 15 epidemiological studies investigating the association of vitamin D and the risk of colon cancer.41 43-45 The majority of studies pointed to a higher risk of colon cancer in individuals whose serum 25-(OH)D3 levels were below the median or in the lowest quartile or quintile. In individuals with serum 25-(OH)D3 levels between 27 and 32 ng/ml, the incidence of colon cancer was reduced by 20% compared to individuals with the lowest 25-(OH)D3 levels. Greater reductions in cancer incidence were observed in individuals with serum levels of 25-(OH)D3 above 55 ng/ml. Of the 11 studies evaluating oral vitamin D intake, 6 indicated a 50% decrease in cancer incidence with intakes equal or greater than 650 IU per day. Although the remaining five studies found no association between vitamin D intake and cancer, three of these five studies were performed in areas with relatively high sunlight exposure. Four studies of the geographic association of sunlight intensity with age-adjusted colon cancer mortality rates found markedly lower rates in sunnier areas, further substantiating the association between sunlight-derived vitamin D levels and colon cancer incidence/mortality.

Current U.S. and Canadian adult dietary reference intakes have been formulated based on the assumption that no endogenous vitamin D is available from sunlight exposure. However, no consideration was given to racial differences in vitamin D-synthesizing capacity, despite the well-established effects of differences in skin pigmentation on endogenous vitamin D synthesis. When Calvo and Barton46 reevaluated the dietary data and serum 25-(OH)D3 levels from the NHANES III study with respect to race (blacks vs. whites), blacks had a significantly higher incidence as well as mortality rates from aggressive cancers compared to that of whites.46 Mean serum 25-(OH)D3 levels of the white

Long/Short (L/S) Poly A microsatellite

Long/Short (L/S) Poly A microsatellite

FIGURE 5.3 Structure of human VDR gene. (Adapted from Price et al.62)

population were 79 ± 0.95 compared to 48.2 ± 1.05 nmol/L in the black population, while average vitamin D intake including food and supplements were 7.92 ± 0.15 and 6.2 ± 0.13 |g/day for white and black populations, respectively.

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