Abstract
The relation between vitamin D status and cancer risk has been investigated in a number of epidemiologic studies, while data from interventional studies remain scarce. The approaches to estimate vitamin D status have been varied and include direct measures of circulating 25-hydroxyvitamin D [25(OH)D] levels, surrogates or determinants of 25(OH)D, including region of residence, intake, and sun exposure estimates. In terms of cancer sites, the body of evidence is most extensive for colorectal cancer, for which support comes from studies of 25(OH)D, vitamin D intake, multiple predictors of 25(OH)D, and region of residence in a sunny climate. The evidence for breast cancer is also intriguing but prospective studies of 25(OH)D are sparse and somewhat conflicting. In one case–control study, retrospectively reported sun exposure during ages 10–19 was most strongly associated with reduced risk of breast cancer. For prostate cancer, the data on circulating 25(OH)D have been equivocal, suggesting no association or a weak inverse association, but studies tend to support a benefit of sun exposure on prostate cancer risk. It is plausible that for prostate cancer, vitamin D level much longer before the time of diagnosis is the most relevant exposure. Most of the epidemiologic studies to date have examined vitamin D status in relation to risk of cancer, but emerging evidence suggests that vitamin D may be an important factor for cancer progression and mortality, independently of any effects on incidence. Further study is needed to establish the precise role of vitamin D on carcinogenesis, especially in terms of when in the life span and on what stages of carcinogenesis vitamin D is relevant, the precise intakes and levels required, the magnitude of the association, and which cancer sites are most affected.
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References
Peller S, Stephenson CS (1937) Skin irritation and cancer in the United States Navy. Am J Med Sci 194:326–333
Apperly FL (1941) The relation of solar radiation to cancer mortality in North America. Cancer Res 1:191–195
Garland CF, Garland FC (1980) Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol 9:227–231
Garland FC, Garland CF, Gorham ED et al (1990) Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev Med 19:614–622
Lefkowitz ES, Garland CF (1994) Sunlight, vitamin D, and ovarian cancer mortality rates in US women. Int J Epidemiol 23:1133–1136
Schwartz GG, Hulka BS (1990) Is vitamin D deficiency a risk factor for prostate cancer? (Hypothesis). Anticancer Res 10:1307–1311
Hanchette CL, Schwartz GG (1992) Geographic patterns of prostate cancer mortality. Cancer 70:2861–2869
Grant WB (2002) An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer 94:1867–1875
Jacobs ET, Haussler MR, Martinez ME (2005) Vitamin D activity and colorectal neoplasia: a pathway approach to epidemiologic studies. Cancer Epidemiol Biomarkers Prev 14:2061–2063
Garland CF, Comstock GW, Garland FC et al (1989) Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet 2:1176–1178
Tangrea J, Helzlsouer K, Pietinen P et al (1997) Serum levels of vitamin D metabolites and the subsequent risk of colon and rectal cancer in Finnish men. Cancer Causes Control 8:615–625
Feskanich D, Ma J, Fuchs CS et al (2004) Plasma vitamin D metabolites and risk of colorectal cancer in women. Cancer Epidemiol Biomarkers Prev 13:1502–1508
Levine AJ, Harper JM, Ervin CM et al (2001) Serum 25-hydroxyvitamin D, dietary calcium in take, and distal colorectal adenoma risk. Nutr Cancer 39:35–41
Peters U, McGlynn KA, Chatterjee N et al (2001) Vitamin D, calcium, and vitamin D receptor polymorphism in colorectal adenomas. Cancer Epidemiol Biomarkers Prev 10:1267–1274
Platz EA, Hankinson SE, Hollis BW et al (2000) Plasma 1,25-dihydroxy- and 25-hydroxyvitamin D and adenomatous polyps of the distal colorectum. Cancer Epidemiol Biomarkers Prev 9:1059–1065
Grau MV, Baron JA, Sandler RS et al (2003) Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trail. J Natl Cancer Inst 95:1765–1771
Braun MM, Helzlsouer KJ, Hollis BW et al (1995) Prostate cancer and prediagnostic levels of serum vitamin D metabolites (Maryland, United States). Cancer Causes Control 6:235–239
Wactawski-Wende J, Kotchen JM, Anderson GL et al (2006) Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 354:684–696
Gorham ED, Garland CF, Garland FC et al (2007) Optimal vitamin D status for colorectal cancer prevention. A quantitative meta analysis. Am J Prev Med 32:210–216
Wu K, Feskanich D, Fuchs CS et al (2007) A nested case–control study of plasma 25-hydroxyvitamin D concentrations and risk of colorectal cancer. J Natl Cancer Inst 99:1120–1129
Otani T, Iwasaki M, Sasazuki S et al (2007) Plasma vitamin D and risk of colorectal cancer: the Japan Public Health Center-Based Prospective Study. Br J Cancer 97:446–451
Freedman DM, Looker AC, Chang SC et al (2007) Prospective study of serum vitamin D and cancer mortality in the United States. J Natl Cancer Inst 99:1594–1602
Peters U, Hayes RB, Chatterjee N et al (2004) Circulating vitamin D metabolites, polymorphism in vitamin D receptor, and colorectal adenoma risk. The Prostate, Lung, Colorectal and Ovarian Cancer Screening Project Team. Cancer Epidemiol Biomarkers Prev 13:546–552
Giovannucci E, Liu Y, Rimm EB, et al (2007) Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst 2006 98:451–459
Garland C, Shekelle RB, Barrett-Conner E et al (1985) Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospective study in men. Lancet 1:307–309
Kearney J, Giovannucci E, Rimm EB et al (1996) Calcium, vitamin D and dairy foods and the occurrence of colon cancer in men. Am J Epidemiol 143:907–917
Bostick RM, Potter JD, Sellers TA et al (1993) Relation of calcium, vitamin D, and dairy food intake to incidence of colon cancer in older women. Am J Epidemiol 137:1302–1317
Martinez ME, Giovannucci EL, Colditz GA et al (1996) Calcium, vitamin D, and the occurrence of colorectal cancer among women. J Natl Cancer Inst 88:1375–1382
Zheng W, Anderson KE, Kushi LH et al (1998) A prospective cohort study of intake of calcium, vitamin D, and other micronutrients in relation to incidence of rectal cancer among postmenopausal women. Cancer Epidemiol Biomarkers Prev 7:221–225
Jarvinen R, Knekt P, Hakulinen T et al (2001) Prospective study on milk products, calcium and cancers of the colon and rectum. Eur J Clin Nutr 55:1000–1007
McCullough ML, Robertson AS, Rodriguez C et al (2003) Calcium, vitamin D, dairy products, and risk of colorectal cancer in the cancer prevention study II nutrition cohort (United States). Cancer Causes Control 14:1–12
Heilbrun LK, Nomura A, Hankin JH et al (1985) Dietary vitamin D and calcium and risk of colorectal cancer (letter). Lancet 1:925
Benito E, Stiggelbout A, Bosch FX et al (1991) Nutritional factors in colorectal cancer risk: a case–control study in Majorca. Int J Cancer 49:161–167
Peters RK, Pike MC, Garabrandt D et al (1992) Diet and colon cancer in Los Angeles County, California. Cancer Causes Control 3:457–473
Ferraroni M, La Vecchia C, D’Avanzo B et al (1994) Selected micronutrient intake and the risk of colorectal cancer. Br J Cancer 70:1150–1155
Boutron MC, Faivre J, Marteau P et al (1996) Calcium, phosphorus, vitamin D, dairy products and colorectal carcinogenesis: a French case–control study. Br J Cancer 74:145–151
Pritchard RS, Baron JA, Gerhardsson de Verdier M (1996) Dietary calcium, vitamin D, and the risk of colorectal cancer in Stockholm, Sweden. Cancer Epidemiol Biomarkers Prev 5:897–900
Marcus PM, Newcomb PA (1998) The association of calcium and vitamin D, and colon and rectal cancer in Wisconsin women. Int J Epidemiol 27:788–793
Kampman E, Slattery ML, Caan B et al (2000) Calcium, vitamin D, sunshine exposures, dairy products and colon cancer risk (United States). Cancer Causes Control 11:459–466
Park SY, Murphy SP, Wilkens LR et al (2007) Calcium, vitamin D, and dairy product intake and prostate cancer risk: the Multiethnic Cohort Study. Am J Epidemiol 166:1259–1269
Freedman DM, Dosemeci M, McGlynn K (2002) Sunlight and mortality from breast, ovarian, colon, prostate, and non-melanoma skin cancer: a composite death certificate based case–control study. Occup Environ Med 59:257–262
Ding EL, Mehta S, Fawzi WW et al (2008) Interaction of estrogen therapy with calcium and vitamin D supplementation on colorectal cancer risk: reanalysis of Women’s Health Initiative randomized trial. Int J Cancer 122:1690–1694
Schwartz GG, Hanchette CL (2006) UV latitude, and spatial trends in prostate cancer mortality: all sunlight is not the same (United States). Cancer Causes Control 17:1091–1101
Corder EH, Guess HA, Hulka BS et al (1993) Vitamin D and prostate cancer: a prediagnostic study with stored sera. Cancer Epidemiol Biomarkers Prev 2:467–472
Gann PH, Ma J, Hennekens CH et al (1996) Circulating vitamin D metabolites in relation to subsequent development of prostate cancer. Cancer Epidemiol Biomarkers Prev 5:121–126
Nomura AM, Stemmermann GN, Lee J et al (1998) Serum vitamin D metabolite levels and the subsequent development of prostate cancer. Cancer Causes Control 9:425–432
Platz EA, Leitzmann MF, Hollis BW et al (2004) Plasma 1,25-dihydroxy- and 25-hydroxyvitamin D and subsequent risk of prostate cancer. Cancer Causes Control 15:255–265
Jacobs ET, Giuliano AR, Martinez ME et al (2004) Plasma levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and the risk of prostate cancer. J Steroid Biochem Mol Biol 89–90:533–537
Ahonen MH, Tenkanen L, Teppo L et al (2000) Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control 11:847–852
Tuohimaa P, Tenkanen L, Ahonen M et al (2004) Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case–control study in the Nordic countries. Int J Cancer 108:104–108
Li H, Stampfer MJ, Hollis BW et al (2007) A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer. PLoS Med 4:e103
Ahn J, Peters U, Albanes D et al (2008) Serum vitamin D concentration and prostate cancer risk: a nested case–control study. J Natl Cancer Inst 100:796–804
Giovannucci E, Rimm EB, Wolk A et al (1998) Calcium and fructose intake in relation to risk of prostate cancer. Cancer Res 58:442–447
Chan JM, Giovannucci E, Andersson SO et al (1998) Dairy products, calcium, phosphorous, vitamin D, and risk of prostate cancer. Cancer Causes Control 9:559–566
Chan JM, Pietinen P, Virtanen M et al (2000) Diet and prostate cancer risk in a cohort of smokers, with a specific focus on calcium and phosphorus (Finland). Cancer Causes Control 11:859–867
Kristal AR, Cohen JH, Qu P et al (2002) Associations of energy, fat, calcium, and vitamin D with prostate cancer risk. Cancer Epidemiol Biomarkers Prev 11:719–725
John EM, Dreon DM, Koo J et al (2004) Residential sunlight exposure is associated with a decreased risk of prostate cancer. J Steroid Biochem Mol Biol 89–90:549–552
John EM, Schwartz GG, Koo J et al (2005) Sun exposure, vitamin D receptor gene polymorphisms, and risk of advanced prostate cancer. Cancer Res 65:5470–5479
Luscombe CJ, Fryer AA, French ME et al (2001) Exposure to ultraviolet radiation: association with susceptibility and age at presentation with prostate cancer. Lancet 358:641–642
Bodiwala D, Luscombe CJ, French ME et al (2003) Associations between prostate cancer susceptibility and parameters of exposure to ultraviolet radiation. Cancer Lett 200:141–148
Rukin N, Blagojevic M, Luscombe CJ et al (2007) Associations between timing of exposure to ultraviolet radiation, T-stage and survival in prostate cancer. Cancer Detect Prev 31(6):443–449
Colston KW, Lowe LC, Mansi JL et al (2006) Vitamin D status and breast cancer risk. Anticancer Res 26:2573–2580
Palmieri C, MacGregor T, Girgis S et al (2006) Serum 25-hydroxyvitamin D levels in early and advanced breast cancer. J Clin Pathol 59:1334–1336
Bertone-Johnson E, Chen WY, Holick MF et al (2005) Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 14:1991–1997
Freedman DM, Chang SC, Falk RT et al (2008) Serum levels of vitamin D metabolites and breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev 17:889–894
Gissel T, Rejnmark L, Mosekilde L et al (2008) Intake of vitamin D and risk of breast cancer: a meta-analysis. J Steroid Biochem Mol Biol Jun 11 (Epub ahead of print)
Shin MH, Holmes MD, Hankinson SE et al (2002) Intake of dairy products, calcium, and vitamin D and risk of breast cancer. J Natl Cancer Inst 94:1301–1310
Laden F, Spiegelman D, Neas LM et al (1997) Geographic variation in breast cancer incidence rates in a cohort of U.S. women. J Natl Cancer Inst 89:1373–1378
John EM, Schwartz GG, Dreon DM et al (1999) Vitamin D and breast cancer risk: the NHANES I Epidemiologic follow-up study, 1971–1975 to 1992. National Health and Nutrition Examination Survey. Cancer Epidemiol Biomarkers Prev 8:399–406
John EM, Schwartz GG, Koo J et al (2007) Sun exposure, vitamin D receptor gene polymorphisms, and breast cancer risk in a multiethnic population. Am J Epidemiol 166:1409–1419
Knight JA, Lesosky M, Barnett H et al (2007) Vitamin D and reduced risk of breast cancer: a population-based case–control study. Cancer Epidemiol Biomarkers Prev 16:422–429
Stolzenberg-Solomon RZ, Vieth R, Azad A et al (2006) A prospective nested case–control study of vitamin D status and pancreatic cancer risk in male smokers. Cancer Res 66:10213–10219
Giovannucci E, Liu Y, Rimm EB et al (2006) Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst 98:451–459
Skinner HG, Michaud DS, Giovannucci E et al (2006) Vitamin D intake and the risk for pancreatic cancer in two cohort studies. Cancer Epidemiol Biomarkers Prev 15:1688–1695
Chen W, Dawsey SM, Qiao YL et al (2007) Prospective study of serum 25(OH)-vitamin D concentration and risk of oesophageal and gastric cancers. Br J Cancer 97:123–128
Abnet CC, Chen W, Dawsey SM et al (2007) Serum 25(OH)-vitamin D concentration and risk of esophageal squamous dysplasia. Cancer Epidemiol Biomarkers Prev 16:1889–1893
Tworoger SS, Lee IM, Buring JE et al (2007) Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of incident ovarian cancer. Cancer Epidemiol Biomarkers Prev 16:783–788
Kricker A, Armstrong BK, Hughes AM et al (2008) Personal sun exposure and risk of non Hodgkin lymphoma: a pooled analysis from the Interlymph Consortium. Int J Cancer 122:144–154
Freedman DM, Zahm SH, Dosemeci M (1997) Residential and occupational exposure to sunlight and mortality from non-Hodgkin’s lymphoma: composite (threefold) case–control study. BMJ 314:1451–1455
Pilz S, Dobnig H, Winklhofer-Roob B et al (2008) Low serum levels of 25-hydroxyvitamin D predict fatal cancer in patients referred to coronary angiography. Cancer Epidemiol Biomarkers Prev 17:1228–1233
Ducloux D, Courivaud C, Bamoulid J et al (2008) Pretransplant serum vitamin D levels and risk of cancer after renal transplantation. Transplantation 85:1755–1759
Trivedi DP, Doll R, Khaw KT (2003) Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomized double blind controlled trial. BMJ 326:469–475
Lappe JM, Travers-Gustafson D, Davies KM et al (2007) Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 85:1586–1591
Whitlatch LW, Young MV, Schwartz GG et al. (2002) 25-Hydroxyvitamin D-1alpha-hydroxylase activity is diminished in human prostate cancer cells and is enhanced by gene transfer. J Steroid Biochem Mol Biol 81:135–140
Chen TC, Wang L, Whitlatch LW et al (2003) Prostatic 25-hydroxyvitamin D-1alpha-hydroxylase and its implication in prostate cancer. J Cell Biochem 88:315–322
Porojnicu A, Robsahm TE, Berg JP et al (2007) Season of diagnosis is a predictor of cancer survival. Sun-induced vitamin D may be involved: a possible role of sun-induced Vitamin D. J Steroid Biochem Mol Biol 103:675–678
Ng K, Meyerhardt JA, Wu K et al (2008) Circulating 25-hydroxyvitamin D levels and survival in patients with colorectal cancer. J Clin Oncol 26:2984–1991
Zhou W, Heist RS, Liu G et al (2007) Circulating 25-hydroxyvitamin D levels predict survival in early-stage non-small-cell lung cancer patients. J Clin Oncol 25:479–485
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Giovannucci, E. (2010). The Epidemiology of Vitamin D and Cancer Risk. In: Holick, M. (eds) Vitamin D. Nutrition and Health. Humana Press. https://doi.org/10.1007/978-1-60327-303-9_42
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DOI: https://doi.org/10.1007/978-1-60327-303-9_42
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