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Relationship Between Vitamin and Calcium Supplement Use and Colon Cancer

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Relationship Between Vitamin and Calcium Supplement Use and Colon Cancer Vol. 6, 769-774, October 1997 Cancer Epidemiology, Biomarkers & Prevention 769 Relationship between Vitamin and Calcium Supplement Use and Colon Cancer Emily White, 2 Jackilen S. Shannon, and Ruth E. Patterson protective effect have not been clearly identified, fruits and Cancer Prevention Research Program, Fred Hutchinson Cancer Research vegetables contain vitamins and minerals that may influence the Center, Seattle, Washington 98104 likelihood of cancer. Laboratory studies suggest a variety of biological mech- anisms by which micronutrients may prevent colon cancer. Abstract Most attention has been given to antioxidant micronutrients The relationship between vitamin supplement use and (including vitamins C and E) as protective agents for cancer (2, colon cancer was assessed in a population-based case- 4, 5). Functions proposed for antioxidants include protection of control study among men and women aged 30-62 years. cell membranes and DNA from oxidative damage and scav- Cases were 251 men and 193 women diagnosed with enging and reduction of nitrites. In addition, vitamins C and E colon cancer in 1985-1989 in three counties in the Seattle have been shown to inhibit experimental colon tumors (6, 7) metropolitan area who were identified from the and to reduce human fecal mutagenic activity (8). Diets defi- Surveillance, Epidemiology, and End Results cancer cient in folic acid may result in hypomethylation of DNA, registry. Controls were 233 men and 194 women which might also be a factor in colon carcinogenesis (9). identified by random digit dialing. Supplement use was Calcium may bind intraluminal bile acids, thereby preventing assessed by questions on frequency, duration, and dose their toxic effects and the resultant compensatory hyperprolif- per day (for individual supplements) or type (for eration (10) or may function to directly reduce cell proliferation multivitamins) during the 10-year period ending 2 years by inducing terminal cell differentiation (11). Similar evidence before diagnosis. All results were adjusted for age and exists for vitamin D in lowering colon cancer risk, because it sex and were not confounded by other measured controls the availability and intracellular functions of calcium behaviors. The average daily intake of supplemental (4). vitamins A, C, E, folic acid, calcium, and multivitamins Studying the effect of vitamin and mineral intake from during the reference period were each associated with supplements in relation to cancer is of interest for several reduced risk of colon cancer (all P for trend <0.03). The reasons. First, supplement use can lead to a higher intake of strongest associations were for use of vitamin E (odds some nutrients than can be obtained from food, which could ratio, 0.43; 95% confidence interval, 0.26-0.71 for >200 lead to a steeper and therefore more detectable gradient of risk. IU/day versus none) and multivitamins (odds ratio, 0.49; Second, supplement intake can be more easily assessed over 95 % confidence interval, 0.35-0.69 for daily use versus time than food intake, and long-term nutrient intake is likely to no use; both P for trend <0.001). These two associations be a greater predictor of cancer risk than intake at a single were also significant using a stricter test of trend limited reference point. Finally, if supplements prove to reduce cancer to supplement users, which reduces the effect of risk, increasing intake of micronutrients by use of vitamin colinearity among these exposures. Because almost all supplements rather than food may be an attractive public health vitamin D supplementation comes from multivitamin strategy. Community and worksite interventions to increase pills, the association of vitamin D use with colon cancer fruit and vegetable consumption have had only modest success could not be distinguished from that of multivitamin use. (12). In contrast, large numbers of Americans are taking sup- Clinical trials or cohort studies with long-term assessment plements (13), although supplement use has not been explicitly would be needed before public health recommendations recommended by scientific or government agencies. could be made about supplement use. Although there is a substantial body of research on diet and colon cancer (1-3), fewer studies have investigated the association of supplement use with colon cancer (14-24), and Introduction none of the observational studies have assessed supplement There is substantial evidence that vitamin and mineral intake intake as cumulative or average dose over a long time frame. may be related to colon cancer risk. Studies of diet and colon We present the association of multivitamin supplements and cancer provide consistent evidence that consumption of fruits specific micronutrients from supplements with colon cancer and vegetables is associated with decreased risk of colon cancer risk from a population-based case-control study in Washington (1-3). Although the specific dietary factors responsible for this State. Detailed assessment of multivitamin and individual sup- plement use over a 10-year reference period was used to esti- mate the dose of supplemental vitamins A, C, E, folic acid, and Received 1/29/97; revised 6/2/97; accepted 6/10/97. calcium. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Materials and Methods 1 Supported by Grants R29 CA44790, N0t CN05230, and T32 CA09661. 2 To whom requests for reprints should be addressed, at Fred Hutchinson Cancer Selection of Cases and Controls. All incident cases of ade- Research Center, 1124 Columbia Street, MP702, Seattle, WA 98104. nocarcinoma of the colon diagnosed between July 1985 and Downloaded from cebp.aacrjournals.org on October 2, 2021. © 1997 American Association for Cancer Research. 770 Supplement Use in Relation to Colon Cancer September 1989 among residents of King, Pierce, or Snoho- mg of vitamin C, 30 IU of vitamin E, 400/xg of folic acid, and mish County aged 30-62 years were identified through the 130 mg of calcium), Theragran (Squibb; 10,000 IU of vitamin Seattle-Puget Sound Surveillance, Epidemiology, and End Re- A, 200 mg of vitamin C, 15 IU of vitamin E, and no folic acid suits registry. Ineligible for the study were patients with ade- or calcium), and Stresstabs (Lederle; 5,000 IU of vitamin A, nocarcinoma of the appendix, the rectosigmoid junction, or the 600 mg of vitamin C, 30 IU of vitamin E, 400 p.g of folic acid, rectum; those with carcinoma in situ; and those with carcinoid and no calcium), respectively (28). Vitamin B complex pills tumors, sarcoma, or lymphoma of the colon. A population and B complex plus C were not considered to be multivitamins control group was selected by a random digit dialing method because they contained no vitamin A, E, or calcium and little based on the one-step Waksberg procedure for survey sam- (100/xg) or no folic acid (27). Vitamin B complex plus C was piing. Inclusion criteria were similar for cases and controls, in coded as 300 mg of vitamin C. The use of calcium containing particular, the absence of antecedent colon or rectal cancer, antacids (Tums), for any purpose, was included in the supple- polyposis, or inflammatory bowel disease; residence in a pri- mental calcium dose, based on questions on years of use, vate household in one of the three selected counties; and ability frequency of use, and brand name. to communicate in English. Because of the small percentage of The average daily dose of each supplemental nutrient was minorities in the area, the study was limited to whites. categorized as no use and two or three levels of use. Because A total of 659 cases were identified. Of these, 102 died 13% of the subjects took a one-a-day-type multivitamin for the before being approached for the study. Among the remaining 10-year period, this group sometimes formed a single category cases, 55 were ineligible (11 had prior colorectal cancer, 10 had of use, e.g., 5000 IU of vitamin A per day is identical to use of polyposis or inflammatory bowel disease, 10 had no phone or a one-a-day-type multivitamin daily for 10 years, as is use of lived outside the Seattle-Puget Sound area, 6 had participated in 100 mg of calcium per day. For each nutrient except folic acid, a prior study, and 4 were not able to communicate adequately). the cutoff for the highest category was selected to represent use For 39 cases, permission to contact was not granted by the greater than that from taking a one-a-day-type multivitamin treating physician, 16 cases refused to participate in the study, daily for the 10-year reference period. For vitamin A, the and 3 were not reachable. Thus, 84.5% of identified cases were highest level (>5000 IU/day) could only be achieved by use of alive, and 88.4% (444 of 502) of alive, potentially eligible cases a therapeutic type of multivitamin or use of individual vitamin completed the interview for an overall estimated case response A supplements; for vitamin C, the highest level of use (->500 proportion of 74.7% (0.845 x 0.884). mg/day) could only be achieved by taking stress-type multivi- Among the controls, household screening to determine tamins or individual vitamin C supplements; for vitamin E, the eligibility was successful for 9051 of the 9384 households highest category (->200 IU/day) represents the equivalent of 5 identified. Of those screened, 549 were selected by stratified years or more daily use of the common dose (400 IU) of random sampling to approximate the age, sex, and residence vitamin E individual supplements; and the highest level of distribution of the cases.
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