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High serum selenium and reduced risk of advanced colorectal adenoma in a colorectal cancer early detection program

Johns Hopkins University, Baltimore, Maryland, United States
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.32). 03/2006; 15(2):315-20. DOI: 10.1158/1055-9965.EPI-05-0471
Source: PubMed

ABSTRACT Epidemiologic and animal studies suggest that selenium may reduce risk of colorectal cancer. However, the epidemiologic data is mainly from relatively small investigations, limiting their interpretation. Although substantial evidence suggests that smoking is a strong effect modifier for other antioxidative nutrients, little is known about smoking-selenium interactions in colorectal tumors.
We studied the association of serum selenium and advanced colorectal adenoma, a cancer precursor, in 758 cases and 767 sex- and race-matched controls, randomly selected from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cases had at least one verified advanced adenoma (> or = 1 cm or villous elements, or high-grade dysplasia) of the distal colon, and controls had a negative sigmoidoscopy.
The multivariable odds ratio (OR) comparing participants in the highest quintile of serum selenium with those in the lowest quintile was 0.76 [95% confidence interval (95% CI), 0.53-1.10; P(trend) = 0.01]. The inverse association between serum selenium and advanced colorectal adenoma was significant among recent smokers (OR, 0.53; 95% CI, 0.27-1.01 for highest versus lowest tertile; P(trend) = 0.008). Serum selenium was unrelated to adenoma risk in nonsmokers and former smokers who quit smoking > or = 10 years ago.
Selenium may reduce the risk of developing advanced colorectal adenoma, particularly among the high-risk group of recent smokers.

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    • "These intakes are not achieved in many countries [1] and sub-optimal selenium intake may have impact on immune function and susceptibility to viral disease and cancers [2]. Both observational and intervention studies suggest that a low selenium status is inversely correlated with an increased colorectal cancer incidence [3] [4] [5]. Furthermore, results of the Nutritional Prevention of Cancer Trial in USA indicated that a daily supplement of 200 mg Se reduced mortality from colorectal cancer [6]. "
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    ABSTRACT: Selenium is an essential micronutrient. Its recommended daily allowance is not attained by a significant proportion of the population in many countries and its intake has been suggested to affect colorectal carcinogenesis. Therefore, microarrays were used to determine how both selenoprotein and global gene expression patterns in the mouse colon were affected by marginal selenium deficiency comparable to variations in human dietary intakes. Two groups of 12 mice each were fed a selenium-deficient (0.086 mg Se/kg) or a selenium-adequate (0.15 mg Se/kg) diet. After 6 wk, plasma selenium level, liver, and colon glutathione peroxidase (GPx) activity in the deficient group was 12, 34, and 50%, respectively, of that of the adequate group. Differential gene expression was analysed with mouse 44K whole genome microarrays. Pathway analysis by GenMAPP identified the protein biosynthesis pathway as most significantly affected, followed by inflammation, Delta-Notch and Wnt pathways. Selected gene expression changes were confirmed by quantitative real-time PCR. GPx1 and the selenoproteins W, H, and M, responded significantly to selenium intake making them candidates as biomarkers for selenium status. Thus, feeding a marginal selenium-deficient diet resulted in distinct changes in global gene expression in the mouse colon. Modulation of cancer-related pathways may contribute to the higher susceptibility to colon carcinogenesis in low selenium status.
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    • "These epidemiology studies have generated both positive and negative results, but do provide substantial support for the hypothesis that Se compounds have cancer preventive activity (Combs, 2005). In recent years, numerous investigators have reported inverse associations between Se biomarkers (toenail Se or serum Se levels) and the risk of neoplasia in several sites, including the prostate (van den Brandt et al., 2003, Vogt et al., 2003, Li et al, 2004), esophagus and gastric cardia (Wei et al., 2004), liver (Sakoda et al., 2005), colon (Ghadirian et al, 2000; Jacobs et al., 2004; Peters et al., 2006), lung (van den Brandt et al., 1993, Zhuo et al., 2004), skin (Burke et al., 1992), and urinary bladder (Zeegers et al., 2002). It should be noted, however, other studies have found no association between Se status and the risk of cancer of the breast (Dorgan et al., 1998; Ghadirian et al, 2000; Männistö et al., 2000), prostate (Ghadirian et al, 2000; Allen et al., 2004), ovary (Pan et al., 2004), non-cardiac stomach (Wei et al., 2004), urinary bladder (Michaud et al., 2002), or lung (Mahabir et al., 2006). "
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    ABSTRACT: Colorectal cancer remains a major cause of cancer related mortality and morbidity. Therefore, primary chemopreven-tion would be a desirable option. Recently, the trace ele-ment selenium (Se), has been evaluated in clinical trials, as a possible chemopreventive agent, in cancer. Several possible mechanisms for its potential anticarcinogenic ef-fects have been proposed, however the exact mechanisms, by which selenium compounds exert these properties, is largely unknown. Results from epidemiological studies have been mixed and inconclusive. The true nature of the association between selenium deficiency and incidence of colorectal adenomas or cancer remains controversial. However, the limited clin-ical data suggest a potential benefit of Se supplementation. Yet, more conclusive evidence is needed before any dietary recommendation can be decided.
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