Abstract
Objective: Calcium, vitamin D, and dairy product intake may reduce the risk of colorectal cancer. We therefore examined the association between these factors and risk of colorectal cancer in a large prospective cohort of United States men and women. Methods: Participants in the Cancer Prevention Study II Nutrition Cohort completed a detailed questionnaire on diet, medical history, and lifestyle in 1992–93. After excluding participants with a history of cancer or incomplete dietary information, 60,866 men and 66,883 women remained for analysis. During follow-up through 31 August 1997 we documented 421 and 262 cases of incident colorectal cancers among men and women, respectively. Multivariate-adjusted rate ratios (RR) were calculated using Cox proportional hazards models. Results: Total calcium intake (from diet and supplements) was associated with marginally lower colorectal cancer risk in men and women (RR = 0.87, 95% CI 0.67–1.12, highest vs lowest quintiles, p trend = 0.02). The association was strongest for calcium from supplements (RR = 0.69, 95% CI 0.49–0.96 for ≥500 mg/day vs none). Total vitamin D intake (from diet and multivitamins) was also inversely associated with risk of colorectal cancer, particularly among men (RR = 0.71, 95% CI 0.51–0.98, p trend = 0.02). Dairy product intake was not related to overall risk. Conclusions: Our results support the hypothesis that calcium modestly reduces risk of colorectal cancer. Vitamin D was associated with reduced risk of colorectal cancer only in men.
Similar content being viewed by others
References
Baron JA,Beach M,Mandel JS, et al. (1999) Calcium supplements for the prevention of colorectal adenomas. N Engl J Med 340: 101-107.
Bonithon-Kopp C,Kronborg O,Giocosa A,Rath U,Faivre J (2000) Calcium and fibre supplementation in the prevention of colorectal adenoma recurrence: a randomised intervention trial. Lancet 356: 1300-1306.
Platz EA,Giovannucci E (1999) Vitamin D and calcium in colorectal and prostate cancers. In: Heber D,Blackburn GL,Go VLW, eds. Nutritional Oncology. San Diego: Academic Press. 223-252.
Wu K,Willett WC,Fuchs CS,Colditz GA,Giovannucci EL (2002) Calcium intake and risk of colon cancer in women and men. J Natl Cancer Inst 94: 437-446.
Bergsma-Kadijk JA,van't Veer P,Kampman E,Burema J (1996) Calcium does not protect against colorectal neoplasia. Epidemiology 7: 590-597.
Martinez ME,Willett WC (1998) Calcium, vitamin D and colorectal cancer: a review of the epidemiologic evidence. Cancer Epidemiol Biomarkers Prev 7: 163-168.
Newmark HL,Wargovich MJ,Bruce WR (1984) Colon cancer and dietary fat, phosphate, and calcium: a hypothesis. J Natl Cancer Inst 72: 1323-1325.
McMichael AJ,Potter JD (1985) Host factors in carcinogenesis: certain bile-acid metabolic profiles that selectively increase the risk of proximal colon cancer. J Natl Cancer Inst 75: 185-191.
Holt PR (1999) Dairy foods and prevention of colon cancer: human studies. J Am Coll Nutr 18: 379S-391S.
Holt PR,Arber N,Halmos B, et al. (2002) Colonic epithelial cell proliferation decreases wtih increasing levels of serum 25-hydroxy vitamin D. Cancer Epidemiol Biomarkers Prev 11: 113-119.
Peters U,McGlynn KA,Chatterjee N, et al. (2001) Vitamin D, calcium, and vitamin D receptor polymorphisms 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.
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.
Cross HS,Peterlik M,Reddy S,Schuster I (1997) Vitamin D metabolism in human colon adenocarcinoma-derived Caco-2 cells: expression of 24-hydroxyvitamin D3-1a-hydroxylase activity and regulation of side-chain metabolism. J Steroid Biochem Mol Biol 62: 21-28.
US Department of Agriculture(1993) USDA's Food Guide, Background and Development, 1514: USDA, Human Information Service.
Jacques PF,Felson DT,Tucker KL, et al. (1997) Plasma 25-hydroxyvitamin D and its determinants in an elderly population sample. Am J Clin Nutr 66: 929-936.
Parodi PW (1997) Cows' milk fat components as potential anticarcinogenic agents. J Nutr 127: 1055-1060.
Outwater JL,Nicholson A,Barnard N (1997) Dairy products and breast cancer: the IGF-I, estrogen, and bGH hypothesis. Med Hypoth 48: 453-461.
Schams D,Karg H (1986) Hormones in milk. Ann NY Acad Sci 464: 75-86.
Chan JM,Stampfer MJ,Ma J,Gann PH,Gaziano J,Giovannucci EL (2001) Dairy products, calcium, and prostate cancer risk in the Physicians' Health Study. Am J Clin Nutr 74: 549-554.
Cramer DW,Greenberg ER,Titus-Ernstoff L, et al. (2000) A case-control study of galactose consumption and metabolism in relation to ovarian cancer. Cancer Epidemiol Biomarkers Prev 9: 95-101.
Boutron MC,Faivre J,Marteau P,Couillault C,Senesse P,Quipourt V (1996) Calcium, phosphorus, vitamin D, dairy products and colorectal carcinogenesis: a French case-control study. Br J Cancer 74: 145-151.
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.
Sellers TA,Bazyk AE,Bostick RM, et al. (1998) Diet and risk of colon cancer in a large prospective study of older women: an analysis stratified on family history. Cancer Causes Control 9: 357-367.
Kampman E,Slattery ML,Caan B,Potter JD (2000) Calcium, vitamin D, sunshine exposure, dairy products and colon cancer risk (United States). Cancer Causes Control 11: 459-466.
Jarvinen R,Knekt P,Hakulinen T,Aromaa A (2001) Prospective study on milk products, calcium and cancers of the colon and rectum. Eur J Clin Nutr 55: 1000-1007.
White E,Shannon J,Patterson R (1997) Relationship between vitamin and calcium supplement use and colon cancer. Cancer Epidemiol Biomarkers Prev 6: 769-774.
Garland C,Barrett-Connor E,Rossof AH,Shekelle RB,Criqui MH,Oglesby P (1985) Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospective study in men. Lancet 1: 307-309.
Heilbrun LK,Nomura A,Hankin JH,Stemmerman GN (1985) Dietary vitamin D and calcium and risk of colorectal cancer. Lancet 1: 925.
Phillips RL,Snowdon DA (1985) Dietary relationships with fatal colorectal cancer among Seventh-Day Adventists. J Natl Cancer Inst 74: 307-317.
Wu AH,Paganini-Hill A,Ross RK,Henderson BE (1987) Alcohol, physical activity and other risk factors for colorectal cancer: a prospective study. Br J Cancer 55: 687-694.
Stemmerman GN,Nomura A,Chyou P-H (1990) The influence of dairy and nondairy calcium on subsite large-bowel cancer risk. Dis Colon Rectum 33: 190-194.
Ursin G,Bjelke E,Heuch I,Vollset SE (1990) Milk consumption and cancer incidence: a Norwegian prospective study. Br J Cancer 61: 454-459.
Kato I,Akhmedkhanov A,Koenig K,Toniolo PG,Shore RE,Riboli E (1997) Prospective study of diet and female colorectal cancer: the New York University Women's Health Study. Nutr Cancer 28: 276-281.
Bostick RM,Potter JD,Sellers TA, et al. (1993) Relation of calcium, vitamin D, and dairy food intake to incidence of colon cancer among older women. Am J Epidemiol 137: 1302-1317.
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.
Calle EE,Rodriguez C,Jacobs EJ, et al. (2002) The American Cancer Society Cancer Prevention Study II Nutrition Cohort-rationale, study design, and baseline characteristics. Cancer 94: 2490-2501.
Bergmann M,Calle E,Mervis C,Miracle-McMahill H,Thun M,Heath C (1998) Validity of self-reported cancers in a prospective cohort study in comparison to data from state cancer registries. Am J Epidemiol 147: 556-562.
Calle EE,Terrell DD (1993) Utility of the National Death Index for ascertainment of mortality among Cancer Prevention Study II participants. Am J Epidemiol 137: 235-241.
Block G,Hartman AM,Naughton D (1990) A reduced dietary questionnaire: development and validation. Epidemiology 1: 58-64.
Kaufman DW,Kelly JP,Rosenberg L,Anderson TE,Mitchell AA (2002) Recent patterns of medication use in the ambulatory adult population of the United States. The Slone Survey. JAMA 287: 337-344.
Block G,Coyl L,Smucker R,Harlan LC (1989) Health Habits and History Questionnaire: diet history and other risk factors. Personal computer system documentation. Bethesda, MD: National Cancer Institute Division of Cancer Prevention and Control, National Institutes of Health.
Agricultural Research Service(1991) Provisional Table on Vitamin D Content of Foods. Beltsville, MD: USDA.
Willett W,Stampfer MJ (1986) Total energy intake: implications for epidemiologic analyses. Am J Epidemiol 124: 17-27.
US Department of Agriculture(1998) Continuing Survey of Food Intakes by Individuals. Agricultural Research Service.
Flagg EW,Coates RJ,Calle EE,Potischman N,Thun MJ (2000) Validation of the American Cancer Society Cancer Prevention Study II Nutrition Survey Cohort Food Frequency Questionnaire. Epidemiology 11: 462-468.
Cox DR (1972) Regression models and life-tables. J R Stat Soc [B], 34: 187-220.
Hosmer D,Lemeshow S (1989) Applied Logistic Regression. New York: John Wiley.
Institute of Medicine(1997) Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D and Fluoride. Washington, DC: National Academy Press.
Speer G,Cseh K,Winkler G,Takacs I,Nagy Z,Lakatos P (2001) Oestrogen and vitamin D receptor (VDR) genotypes and the expression of ErbB-2 and EGF receptor in human rectal cancers. Eur J Cancer 37: 1463-1468.
Makishima M,Lu TT,Xie W, et al. (2002) Vitamin D receptor as an intestinal bile acid sensor. Science 296: 1313-1316.
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.
Bostick RM,Potter JD,Fosdick L, et al. (1993) Calcium and colorectal epithelial cell proliferation: a preliminary randomized, double-blinded, placebo-controlled clinical trial. J Natl Cancer Inst 85: 132-141.
Bostick RM (1997) Human studies of calcium supplementation and colorectal epithelial cell proliferation. Cancer Epidemiol Biomarkers Prev 6: 971-980.
Alder RJ,McKeown-Eyssen G,Bright-See E (1993) Randomized trial of the effect of calcium supplementation on fecal risk factors for colorectal cancer. Am J Epidemiol 138: 804-814.
Alberts DS,Ritenbaugh C,Story JA, et al. (1996) Randomized, double-blinded, placebo-controlled study of effect of wheat bran fiber and calcium on fecal bile acids in patients with resected adenomatous colon polyps. J Natl Cancer Inst 88: 81-92.
Holt PR,Atillasoy EO,Gilman J, et al. (1998) Modulation of abnormal colonic epithelial cell proliferation and differentiation by low-fat dairy foods. JAMA 280: 1074-1079.
Food Surveys Research Group, and Service AR(1999) Pyramid Servings Data: results from USDA's 1994-96 continuing survey of food intakes by individuals. Beltsville,MD: US Department of Agriculture.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
McCullough, M.L., Robertson, A.S., Rodriguez, C. et al. 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 (2003). https://doi.org/10.1023/A:1022591007673
Issue Date:
DOI: https://doi.org/10.1023/A:1022591007673