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High Serum Selenium and Reduced Risk of Advanced Colorectal Adenoma in a Colorectal Cancer Early Detection Program

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High Serum Selenium and Reduced Risk of Advanced Colorectal Adenoma in a Colorectal Cancer Early Detection Program 315 High Serum Selenium and Reduced Risk of Advanced Colorectal Adenoma in a Colorectal Cancer Early Detection Program Ulrike Peters,1,2,3 Nilanjan Chatterjee,1 Timothy R. Church,4 Charlotte Mayo,5 Stefan Sturup,6,7 Charles B. Foster,7,8 Arthur Schatzkin,1 and Richard B. Hayes1 1Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Rockville Maryland; 2Cancer Prevention Program, Fred Hutchinson Cancer Research Center Seattle, Washington; 3Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington; 4Division of Environmental and Occupational Health, University of Minnesota, School of Public Health, Minneapolis, Minnesota; 5Department of Medicine, Division of Preventive Medicine, University of Alabama, Birmingham, Alabama; 6Dartmouth Trace Element Analysis Core Facility, Dartmouth College, Hanover, New Hampshire; 7Institute of Analytical Chemistry, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark; and 8Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland Abstract Background: Epidemiologic and animal studies suggest that Results: The multivariable odds ratio (OR) comparing selenium may reduce risk of colorectal cancer. However, the participants in the highest quintile of serum selenium with epidemiologic data is mainly from relatively small inves- those in the lowest quintile was 0.76 [95% confidence tigations, limiting their interpretation. Although substantial interval (95% CI), 0.53-1.10; Ptrend = 0.01]. The inverse evidence suggests that smoking is a strong effect modifier association between serum selenium and advanced colorec- for other antioxidative nutrients, little is known about tal adenoma was significant among recent smokers (OR, 0.53; smoking-selenium interactions in colorectal tumors. 95% CI, 0.27-1.01 for highest versus lowest tertile; Ptrend = Methods: We studied the association of serum selenium and 0.008). Serum selenium was unrelated to adenoma risk in advanced colorectal adenoma, a cancer precursor, in 758 cases nonsmokers and former smokers who quit smoking z10 and 767 sex- and race-matched controls, randomly selected years ago. from the Prostate, Lung, Colorectal, and Ovarian Cancer Conclusion: Selenium may reduce the risk of developing Screening Trial. Cases had at least one verified advanced advanced colorectal adenoma, particularly among the high- adenoma (z1 cm or villous elements, or high-grade dysplasia) risk group of recent smokers. (Cancer Epidemiol Bio- of the distal colon, and controls had a negative sigmoidoscopy. markers Prev 2006;15(2):315–20) Introduction Colorectal cancer is the third most commonly diagnosed concentration of the soil where the crops are grown (3-5), with cancer in U.S. men and women, leading to >50,000 deaths high selenium soil content, for example, in Nebraska, the annually (1, 2). Identifying modifiable risk factors is important Dakotas, and Colorado, and lower content in the South and for the prevention of this disease. Northeast of the United States (6, 7). U.S. population intakes Interest in the essential trace element selenium as a range between 50 and 250 Ag/d (8-10), encompassing levels colorectal cancer preventive agent was stimulated by the within the dosing level (200 Ag/d) associated with colorectal observation of a 61% reduction in colorectal cancer in the cancer prevention in the Nutritional Prevention of Cancer Trial treatment arm of the Nutritional Prevention of Cancer Trial, a (11, 12). randomized placebo controlled trial for skin cancer prevention A recent pooled analysis (13) of 1,012 cases of recurrent with selenium supplementation (200 Ag selenium per day). colorectal adenoma showed an inverse association between This result is limited, however, in that colorectal cancer was serum/plasma selenium and adenoma recurrence, with a not a primary end point of the trial, and the number of preponderance of less advanced tumors. Pooled risk estimates colorectal cancer cases was small (selenium arm = 8, placebo indicate a stronger association for advanced adenoma; arm = 19). however, the power was limited (13). To examine associations Most observational studies investigating selenium exposure between serum selenium and risk for advanced colorectal are small, because reliable data on selenium is largely adenoma (i.e., tumors with a greater potential for malignant restricted to selenium measures in biological tissues, due to transformation), we studied more than 750 advanced colorec- large variations in the selenium content of foods resulting in tal adenoma cases and controls. Our interest was to explore imprecise dietary selenium intake estimates from question- interactions of selenium with tobacco use, because substantial naires (3-5). The selenium levels of U.S. grains, dairy products, evidence from animal and human studies, including random- eggs, meat, poultry, and fish-all good sources of selenium-vary ized trials, suggests that smoking is a strong effect modifier for up to 10-fold, as a result of differences in the selenium other antioxidative nutrients, including h-carotene and vita- min E (reviewed in ref. 14). This case-control study was nested in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, in which Received 6/23/05; revised 11/20/05; accepted 12/27/05. colorectal adenoma were identified following a standard 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. protocol in a large population characterized for colorectal Section 1734 solely to indicate this fact. cancer risk factors. Because the trial is conducted at 10 Requests for reprints: Ulrike Peters, Cancer Prevention Research Program, Fred Hutchinson centers throughout the United States, it also captures the Cancer Research Center Research, P.O. Box 19024, 1100 Fairview Avenue North M4-B402, Seattle, WA 98109-1024. Phone: 206-667-2450; Fax: 206-667-7850. E-mail: [email protected] wide geographic differences in selenium intake in the U.S. Copyright D 2006 American Association for Cancer Research. population, which increase the power to detect an associa- doi:10.1158/1055-9965.EPI-05-0471 tion (6, 7). Cancer Epidemiol Biomarkers Prev 2006;15(2). February 2006 Downloaded from cebp.aacrjournals.org on September 25, 2021. © 2006 American Association for Cancer Research. 316 Selenium and Colorectal Adenoma Materials and Methods between selenium and colorectal adenoma, we calculated odds ratios (OR) and 95% confidence intervals (95% CI) using This case-control study was nested within the Prostate, Lung, unconditional logistic regression analysis, with selenium Colorectal, and Ovarian Cancer Screening Trial, which was entered as a continuous variable or in quintiles, with cut designed to evaluate selected methods for the early detection points based on the selenium distribution in controls. We used of these cancers and to investigate etiologic factors and early the continuous variable to estimate for a linear trend. All Ps markers of cancer (15, 16). Participants in the Prostate, Lung, are two sided. Colorectal, and Ovarian Cancer Screening Trial, ages 55 to 74 The ORs were adjusted for the matching factors, sex, and years, were recruited at 10 centers in the United States race, and in addition for age at randomization, study center, (Birmingham, AL; Denver, CO; Detroit, MI; Honolulu, HI; and year of blood draw. We evaluated confounding for Marshfield, WI; Minneapolis, MN; Pittsburgh, PA; Salt Lake known and potential risk factors of colorectal tumors, City, UT; St Louis, MO; and Washington, DC). Participants in including physical activity, body mass index, smoking, the screening arm of the trial received sigmoidoscopic exam at alcohol intake, aspirin use, ibuprofen use, hormone replace- baseline. If the sigmoidoscopy identified polyps or other ment therapy (women only), family history of colorectal suspect lesions, participants were advised to get further cancer, race, educational attainment, energy intake, red meat follow-up examination through their own medical care intake, folate intake, fiber intake, and calcium intake. None of providers, which usually resulted in a full colonoscopy with the factors was included in the analyses because none polypectomy or surgical procedures, if indicated. All medical of them changed the b coefficient of the risk estimates of and pathologic reports of the follow-up examinations were selenium by >10%. Because the variation of the quality obtained and coded by trained medical record abstractors. control samples in the last 16 batches was substantially larger Written informed consent was obtained from participants, and than in the first 180 batches (SD = 24.5 and 8.4, respectively), the trial received approval from the institutional review boards we included an indicator variable for this batch effect of the U.S. National Cancer Institute and the 10 study centers. [excluding participants analyzed in the last 16 batches (7.5% of all participants) did not change the association between Study Population. All cases and controls for this study were selenium and adenoma risk]. selected from 42,037 participants in the screening group who Selenium levels are reported to be related to age, sex, underwent a successful sigmoidoscopic examination at base- smoking, and alcohol consumption (9, 10, 21, 22). Furthermore, line (insertion to at least 50
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