Some of the gradient for breast cancer may be associated with reproductive factors. Normal colon, — breast, , and prostate epithelial cells have a vitamin D receptor VDR that is highly sensitive to 1,25 OH 2 D. This could provide a mechanism of anticarcinogenic action for either circulating or locally synthesized 1,25 OH 2 D. Because synthesis of circulating 1,25 OH 2 D is regulated in the kidney by parathyroid hormone, increased UVB exposure usually does not elevate circulating 1,25 OH 2 D.
The fact that 1,25 OH 2 D is synthesized in colon epithelium provides a possible explanation for lower incidence rates of colon cancer 50 — 52 and adenomatous polyps 67 — 69 in individuals with higher levels of serum 25 OH D.
It also helps explain the association of residence at sunnier latitudes with lower mortality rates from colon, 12 , 17 , 56 , 64 breast, 13 , 14 , 17 , 64 , 85 ovary, 15 , 17 , 64 and prostate 16 , 17 , 64 , 87 , 90 , 91 cancer, because sunlight increases 25 OH D levels, thereby providing more substrate for these tissues to make 1,25 OH 2 D.
Blacks have levels of 25 OH D approximately half those of Whites. There is a possibility of confounding by stage at diagnosis, since breast cancer tends to be diagnosed in more advanced stages in Blacks than in Whites.
There are several VDR genotypes. In men below the median serum 25 OH D level, those with the bb genotype had more than twice the incidence of prostate cancer as other men. VDR polymorphisms also are associated with a more severe form of malignancy. These studies have helped define the role of vitamin D in cancer, , , , although most were exploratory, and only a few of the known VDR genotypes have been shown to be associated with risk of cancer.
One study reported a trend toward higher risk of colon cancer with lower vitamin D intake, 71 and another reported an inverse association of vitamin D and calcium intake with risk of rectal cancer. Although the latitude gradient helps to isolate the role of vitamin D, confounding is still possible. Residents of sunny areas, 16 , 87 and those with a history of exposure to high levels of sunlight, 92 , 95 , had lower risk of prostate cancer. Vitamin D and its metabolites reduce the incidence of many types of cancer by inhibiting tumor angiogenesis, — stimulating mutual adherence of cells, and enhancing intercellular communication through gap junctions, thereby strengthening the inhibition of proliferation that results from tight physical contact with adjacent cells within a tissue contact inhibition.
Vitamin D metabolites help maintain a normal calcium gradient in the colon epithelial crypts, and high serum levels of 25 OH D are associated with markedly decreased proliferation of noncancerous but high-risk epithelial calls in the colon.
The National Academy of Sciences recommends the following daily intakes of vitamin D: 1 to 50 years of age, international units IU ; 51 to 70 years, IU; older than 71 years, IU. Althought adverse VDR genotypes , — , are present in a large proportion of the population, , different intakes according to genotype would not be practical. Older adults need higher amounts of vitamin D owing to decreased absorption, and at any age, serum 25 OH D rises as an inverse power function of vitamin D intake.
Blacks require twice as long. Moderation is needed concerning sunlight exposure. Actinic changes are associated with exposure to ultraviolet radiation, and there is considerable evidence for its role in skin cancer. Individuals with skin type I or II, who tend to burn easily and tan poorly, should not exceed 20 minutes per day in the sun.
Exposure times much longer than 20 minutes would not appreciably increase vitamin D synthesis and could increase risk of skin cancer. Vitamin D dosages of up to IU per day have no reasonable likelihood of producing toxicity.
Potential toxic effects of vitamin D overdosage, such as bone demineralization, hypercalcemia, hypercalciuria, or nephrocalcinosis with renal failure, are encountered rarely, generally only when the daily dose exceeds 10 IU of vitamin D on a chronic basis.
Relatively high oral intakes of vitamin D or serum levels of 25 OH D are not a concern from a cardiovascular viewpoint, because most studies suggest that higher levels of 25 OH D are associated with reduced cardiovascular risk. For example, higher serum 25 OH D, 1,25 OH 2 D, , and oral vitamin D were associated with moderately but significantly lower blood pressure.
There also was a beneficial association between serum 25 OH D and risk of myocardial infarction, ischemic heart disease mortality, and congestive heart failure, although other cardiovascular results have been mixed. Vitamin D supplementation was also associated with reduced incidence of type I diabetes , and with improvement in type II diabetes.
Supplemental vitamin D intake could address the high prevalence of vitamin D deficiency in the United States. More than laboratory and epidemiological studies have been published concerning the association between vitamin D and its metabolites and cancer. Long-term studies have demonstrated the efficacy of moderate intake of vitamin D in reducing cancer risk and, when administered with calcium, in reducing the incidence of fractures.
The cost of a daily dose of vitamin D 3 IU is less than 5 cents, which could be balanced against the high human and economic costs of treating cancer attributable to insufficiency of vitamin D.
Leadership from the public health community will provide the best hope for action. The authors thank William B. The views expressed in this report are those of the authors and do not represent an official position of the Department of the Navy, Department of Defense, or the US Government.
Contributors C. Garland, F. Garland, and E. Gorham jointly developed the plan and outline of the article, prepared the first draft, and reviewed and edited subsequent drafts. Mohr and C. Garland jointly performed the literature review, and S. Mohr edited drafts of the article. Lipkin, H. Newmark, and M. Holick reviewed and edited drafts.
National Center for Biotechnology Information , U. Am J Public Health. Garland , PhD, Edward D. Holick , MD, PhD. Garland Cedric F. Find articles by Cedric F. Frank C. Find articles by Frank C. Edward D. Gorham Cedric F. Find articles by Edward D. Martin Lipkin Cedric F. Find articles by Martin Lipkin. Harold Newmark Cedric F. Find articles by Harold Newmark. Sharif B. Mohr Cedric F. Find articles by Sharif B. Holick Cedric F. Find articles by Michael F.
Author information Article notes Copyright and License information Disclaimer. Accepted January 18, This article has been cited by other articles in PMC. Abstract Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. Open in a separate window.
Notes Peer Reviewed Contributors C. References 1. Utiger R. The need for more vitamin D. N Engl J Med. Holick MF. Too little vitamin D in premenopausal women: why should we care? Am J Clin Nutr. Compston J. Vitamin D deficiency: time for action. Evidence supports routine supplementation for elderly people and others at risk.
Wharton B. Low plasma vitamin D in Asian toddlers in Britain. Garabedian M, Ben-Mehkbi H. Rickets and vitamin D deficiency. In: Holick M, ed. Totowa, NJ: Humana; — Holick M. Vitamin D and bone health. J Nutr. Studies on experimental rickets, XXI: an experimental demonstration of the existence of a vitamin which promotes calcium deposition.
J Biol Chem. Cancer Epidemiol Biomarkers Prev. Lipkin M, Newmark HL. Vitamin D, calcium and prevention of breast cancer: a review.
J Am Coll Nutr. Cancer chemoprevention using natural vitamin D and synthetic analogs. Annu Rev Pharmacol Toxicol. Vitamin D and cancer: effects of 1,25 OH 2D3 and its analogs on growth control and tumorigenesis. Front Biosci. Garland C, Garland F. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol. Acid haze air pollution and breast and colon cancer in 20 Canadian cities. Can J Public Health. Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation.
Prev Med. Sunlight, vitamin D, and ovarian cancer mortality rates in US women. Is vitamin D deficiency a risk factor for prostate cancer? Anticancer Res. Grant WB. An estimate of premature cancer mortality in the US because of inadequate doses of solar ultraviolet-B radiation. The use and interpretation of assays for vitamin D and its metabolites. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, — Low serum hydroxyvitamin D in blacks results from decreased production rate and not increased metabolic clearance rate [abstract].
J Bone Miner Res. Mitra D, Bell N. Racial, geographic, genetic and body habitus effects on vitamin D metabolism. Vitamin D. San Diego, Calif: Academic Press; — Biochemical and hormonal variables in black and white women matched for age and weight.
J Lab Clin Med. Vitamin D supplementation in postmenopausal black women. J Clin Endocrinol Metab. The impact of atmospheric pollution on vitamin D status of infants and toddlers in Delhi, India. Arch Dis Child. Wintertime vitamin D deficiency in male adolescents: effect on parathyroid function and response to vitamin D3 supplements.
Osteoporos Int. Seasonal fluctuations in serum concentrations of vitamin D metabolites in normal subjects. Br Med J. Low serum concentrations of hydroxyvitamin D in young adult Japanese women: a cross sectional study. Longitudinal evaluation of vitamin D status in healthy subjects from southern Italy: seasonal and gender differences.
Wintertime vitamin D insufficiency is common in young Canadian women, and their vitamin D intake does not prevent it. Eur J Clin Nutr. Vitamin D insufficiency in a population of healthy western Canadians. Assessment of vitamin D and calcium status in healthy adult Austrians. Eur J Clin Invest. Elderly women in northern New England exhibit seasonal changes in bone mineral density and calciotropic hormones. Bone Miner. Decreased bioavailability of vitamin D in obesity.
Hypovitaminosis D and vitamin D deficiency in exclusively breast-feeding infants and their mothers in summer: a justification for vitamin D supplementation of breast-feeding infants. Some lymph nodes are deep inside the body, such as between the lungs or around the bowel, to filter fluid in those areas.
Swollen lymph nodes lymphadenopathy tell you that something is not right, but other symptoms help pinpoint the problem. For instance, ear pain, fever, and enlarged lymph nodes near your ear are clues that you may have an ear infection or cold. Some areas where lymph nodes commonly swell are in the neck, groin, and underarms. In most cases, only one area of nodes swells at a time. Some infections such as strep throat and chicken pox , certain medicines, immune system diseases, and cancers like lymphoma and leukemia can cause this kind of swelling.
Your health care provider will look for more information to figure out the cause of the swelling. Lymph node swelling is often caused by something other than cancer. Cancer can appear in the lymph nodes in 2 ways: it can either start there or it can spread there from somewhere else. Cancer that starts in the lymph nodes is called lymphoma. More often, cancer starts somewhere else and then spreads to lymph nodes. That is the focus of this section. When cancer cells break away from a tumor, they can travel to other areas through either the bloodstream or the lymph system.
If they travel through the lymph system, the cancer cells may end up in lymph nodes. Most of the escaped cancer cells die or are killed before they can start growing somewhere else. But one or two might settle in a new area, begin to grow, and form new tumors.
This spread of cancer to a new part of the body is called metastasis. It describes 8 cases of tumors or ulcers of the breast that were removed by cauterization with a tool called the fire drill. In Greek, these words refer to a crab, most likely applied to the disease because the finger-like spreading projections from a cancer called to mind the shape of a crab.
Galen AD , another Greek physician, used the word oncos Greek for swelling to describe tumors. During the Renaissance, beginning in the 15th century, scientists developed greater understanding of the human body.
Scientists like Galileo and Newton began to use the scientific method, which later was used to study disease. Autopsies, done by Harvey , led to an understanding of the circulation of blood through the heart and body that had until then been a mystery.
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