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: 4.13). 03/2006; 15(2):315-20. DOI: 10.1158/1055-9965.EPI-05-0471
Source: PubMed


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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    • "and 0.44 (95% CI 0.24-0.81) were found for the lowest quintile of baseline selenium and current smokers, respectively [68]. Finally a more recent double-blind randomized trial conducted on 411 patients who had undergone a polypectomy, showing that the co-administration of selenium with other antioxidants significantly reduced the risk of adenoma recurrence in these patients (HR 0.61; 95 % CI 0.41-0.92) "
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    ABSTRACT: Background Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality. People at higher risk are those individuals with a family history of CRC and familial adenomatous polyposis. Prevention and screening are two milestones for this disease. The aim of this study is to evaluate the chemopreventive role of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin and cyclooxygenase 2 inhibitors, some micronutrients (folic acid, calcium, selenium, antioxidants) and probiotics. Discussion The studies on aspiring reported promising results, but it is debatable whether aspirin should be used as chemoprevention, because of its side effects and because of poor efficacy evident in subjects at high risk. Similar results were reported for other non-aspirin NSAIDs, such as sulindac and celecoxib, which the potential adverse effects limit their use. Selenium role in prevention of various types of cancer as well as in colon adenomas are often inconclusive or controversial. Several studies suggested that calcium may have a possible chemopreventive effect on colon adenomas and CRC, although contrasting results are reported for the latter. A recent meta-analysis including 13 randomized trial suggested that folic acid supplementation had not a chemiopreventive action on CRC. Several studies investigated the association between antioxidants, administered alone or in combination, and CRC risk, both among general and at risk population, but only few of them supported statistically significant results. Conclusion The results of this literature review showed an unclear role in CRC prevention of both pharmacological and dietary intervention. Despite several options are available to prevent colon cancer, it is challenging to identify a correct strategy to prevent CRC through pharmacological and dietary intervention due to the long latency of cancer promotion and development. Since some of the drugs investigated may have uncertain individual effects, it can be suggested to potentiate such effects by adding them together.
    BMC Surgery 10/2013; 13 (suppl 2)(S16). DOI:10.1186/1471-2482-13-S2-S16 · 1.40 Impact Factor
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    • "There is evidence from epidemiologic, clinical and preclinical studies that dietary supplementation with the essential trace mineral selenium reduces the incidence and mortality of colon cancer in humans [4], [5]. Previous animal studies have demonstrated protective effects of selenium fortification against aberrant crypt formation and colon tumor development [5]–[8]. Recent studies indicate that both low molecular weight selenocompounds and selenium-containing proteins (selenoproteins) can mediate the cancer-protective effects of selenium in the colon [9]. "
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    ABSTRACT: Evidence suggests that selenium has cancer preventive properties that are largely mediated through selenoproteins. Our previous observations demonstrated that targeted down-regulation of the 15 kDa selenoprotein (Sep15) in murine colon cancer cells resulted in the reversal of the cancer phenotype. The present study investigated the effect of Sep15 knockout in mice using a chemically-induced colon cancer model. Homozygous Sep15 knockout mice, and wild type littermate controls were given four weekly subcutaneous injections of azoxymethane (10 mg/kg). Sep15 knockout mice developed significantly (p<0.001) fewer aberrant crypt foci than controls demonstrating that loss of Sep15 protects against aberrant crypt foci formation. Dietary selenium above adequate levels did not significantly affect aberrant crypt foci formation in Sep15 knockout mice. To investigate molecular targets affected by loss of Sep15, gene expression patterns in colonic mucosal cells of knockout and wild type mice were examined using microarray analysis. Subsequent analyses verified that guanylate binding protein-1 (GBP-1) mRNA and protein expression were strongly upregulated in Sep15 knockout mice. GBP-1, which is expressed in response to interferon-γ, is considered to be an activation marker during inflammatory diseases, and up-regulation of GBP-1 in humans has been associated with a highly significant, increased five-year survival rate in colorectal cancer patients. In agreement with these studies, we observed a higher level of interferon-γ in plasma of Sep15 knockout mice. Overall, our results demonstrate for the first time, that Sep15 knockout mice are protected against chemically-induced aberrant crypt foci formation and that Sep15 appears to have oncogenic properties in colon carcinogenesis in vivo.
    PLoS ONE 12/2012; 7(12):e50574. DOI:10.1371/journal.pone.0050574 · 3.23 Impact Factor
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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.
    Molecular Nutrition & Food Research 10/2009; 53(12):1561 - 1572. DOI:10.1002/mnfr.200900105 · 4.60 Impact Factor
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