Variation in the Selenoenzyme Genes and Risk of Advanced Distal Colorectal Adenoma

Peters, Ulrike; Chatterjee, Nilanjan; Hayes, Richard B.; Schoen, Robert E.; Wang, Yinghui; Chanock, Stephen J.; Foster, Charles B.

doi:10.1158/1055-9965.epi-07-2947

Cited by 105 publications

(90 citation statements)

References 71 publications

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“…Variants of a SNP in the promoter of the selenoprotein P gene (SEPP1) were not associated with altered risk of CRC [1], but a more recent study indicated that three variants in SEPP1 and one in the thioredoxin reductase 1 gene TXNRD1 showed an association with risk of adenoma [22]. In addition, a relatively small case-control study in the United Kingdom showed an association of the C variant of rs713041 in GPX4 with increased risk of CRC [3].…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the selenoprotein S and 15-kDa selenoprotein genes are associated with altered susceptibility to colorectal cancer

et al. 2010

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Selenium (Se), a dietary trace metal essential for human health, is incorporated into *25 selenoproteins including selenoprotein S (SelS) and the 15-kDa selenoprotein (Sep15) both of which have functions in the endoplasmic reticulum protein unfolding response. The aim of this study was to investigate whether genetic variants in such selenoprotein genes are associated with altered risk of colorectal cancer (CRC). A Korean population of 827 patients with CRC and 733 healthy controls was genotyped for 7 SNPs in selenoprotein genes and one SNP in the gene encoding manganese superoxide dismutase using Sequenom technology. Multivariate logistic regression analysis showed that after adjustment for lifestyle factors three SNP variants were associated with altered disease risk. There was a mean odds ratio of 2.25 [95% CI 1.13,4.48] in females homozygous TT for rs34713741 in SELS with the T variant being associated with higher risk of rectal cancer, and odds ratios of 2.47 and 2.51, respectively, for rs5845 and rs5859 in SEP15 with the minor A and T alleles being associated with increased risk of male rectal cancer. The data indicate that the minor alleles for rs5845, rs5859 and rs34713741 are associated with increased rectal cancer risk and that the effects of the three SNPs are dependent on gender. The results highlight potential links between Se, the function of two selenoproteins involved in the protein unfolding response and CRC risk. Further studies are required to investigate whether the effects of the variants on CRC risk are also modulated by dietary Se intake.

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Section: Introductionmentioning

confidence: 99%

Polymorphisms in the selenoprotein S and 15-kDa selenoprotein genes are associated with altered susceptibility to colorectal cancer

et al. 2010

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“…Over-expression of GPX-1 is associated with a wide range of effects, including the prevention of apoptosis, the protection against toxicity and the reduction of DNA damage (Zhuo, et al, 2009). Given human epidemiological data indicating significant associations between polymorphisms in GPx-1 and the risk of several cancer types due to the important biological activities of the essential trace element selenium are mediated through the function of selenoenzymes (Ichimura, et al, 2004;Hu & Diamond, 2003;Mak, et al, 2006;Choi, et al, 2007;Peters, et al, 2008). In this article we show the relationship between the presence of the Pro198Leu variant of the GPX-1 gene and its association with the risk of developing bladder cancer.…”

Section: Resultsmentioning

confidence: 78%

Epidemiology and Polymorphisms Related to Bladder Cancer in Ecuadorian Individuals

Paz‐y‐Miño¹,

Muñoz²

2012

Bladder Cancer - From Basic Science to Robotic Surgery

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“…In the murine intestine, GPx4 mRNA is one of the most abundant selenoprotein transcripts (8); genetic variant analysis of the human GPX4 gene links it to malignant disease risk in the gastrointestinal tract (9,11). Investigation of intestinal GPx4 has so far been limited to the mRNA level (33,36) and to the measurement of GPx4 activity in mouse tissue homogenates (44).…”

Section: Discussionmentioning

confidence: 99%

“…A constant level of GPx4 mRNA during periods of limited selenium availability as against the concomitant degradation of other GPx isoforms such as GPx1 reflects the high ranking of GPx4 in the so-called selenoprotein hierarchy (32) and argues for an important role of this protein in enterocytes. Intriguingly, a function of GPx4 as a candidate mediator of selenium-dependent chemoprevention in the colon arises from studies on the association of a single nucleotide polymorphism (rs713041) in the human GPX4 gene with colorectal adenoma and colorectal cancer risk (9,11,18). The enzymatic capacity of GPx4 extends beyond those of other hydroperoxide-degrading GPx isoforms.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, a role for GPx4 in the prevention of mutagenesis has been suggested; GPx4 repairs oxidatively damaged DNA by reduction of thymine hydroperoxide (16), and increased levels of mutagenic DNA adducts have been detected in murine embryonic fibroblast cells from GPx4 ϩ/Ϫ mice (17). A functional variant of the human GPX4 gene has been identified (18), which is associated with increased risk of colorectal adenoma and colorectal cancer (9,11). The relevance of an adequate GPx4 expression for colon tissue homeostasis in humans notwithstanding information on protein expression, localization, and regulation of GPx4 in enterocytes is limited.…”

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Induction of Glutathione Peroxidase 4 Expression during Enterocytic Cell Differentiation

Speckmann¹,

Bidmon²,

Pinto³

et al. 2011

Journal of Biological Chemistry

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Glutathione peroxidase 4 (GPx4), an abundant selenoenzyme, is ubiquitously expressed in a tissue-, cell-and differentiationdependent manner, and it is localized in cytoplasmic, mitochondrial, and nuclear cellular compartments. Here, we report cytoplasmic and nuclear localization of GPx4 in Caco-2 intestinal epithelial cells. Enterocytic differentiation of Caco-2 cells triggers an increase in GPx4 mRNA and protein levels, mediated by enhanced promoter activity. We identified a combined cAMP response element (CREB) and CCAAT/enhancer binding protein (C/EBP) site as critical for the differentiation-triggered GPx4 promoter activity. Induction of GPx4 correlated with C/EBP␣ transcript levels during differentiation, suggesting a role of C/EBP␣ as regulator of enterocytic GPx4 expression. Consistent with the in vitro results, GPx4 protein was detected in cytoplasmic and nuclear compartments of enterocytes in human intestinal epithelia. GPx4 is uniformly expressed in colonic crypts and is differentially expressed along the cryptto-villus axis in the small intestine with a more pronounced expression of GPx4 in the upper villi, which contain fully differentiated enterocytes. These data suggest that intestinal GPx4 expression is modulated by the enterocytic differentiation program, and the results support a direct role of nuclear GPx4 in the (selenium-dependent) prevention of oxidative damage in the gastrointestinal tract.The essential trace element selenium is of fundamental importance to human health, acting through low molecular weight selenium compounds as well as selenocysteine-containing selenoproteins (1). Adequate selenium intake, maintaining optimized expression and/or activity of selenoproteins, has been proposed to be beneficial with respect to prevention of several oxidative stress-related neurodegenerative and cardiovascular diseases and, most notably, cancer (1, 2). Secondary end point analyses of the Nutritional Prevention of Cancer study provided compelling evidence that dietary supplementation with 200 g selenium/day in form of high selenium yeast lowered the incidence of lung, prostate, and colorectal cancer as well as cancer mortality (3). Since the publication of this landmark trial, the anticarcinogenic capacity of selenium compounds has been further substantiated, particularly with regard to the gastrointestinal tract (4 -7). Mice with genetically impaired biosynthesis of selenoproteins due to a mutant selenocysteine transfer RNA gene have been shown to be more susceptible to colon cancer than wild-type mice, thus suggesting a key role for selenoproteins as mediators of the cancer-protective effects of selenium in the colon (5). Selenoproteins that are abundantly expressed in the healthy gastrointestinal tract and putatively relevant in malignant transformation comprise thioredoxin reductases, selenoprotein P, and glutathione peroxidases (GPx) 3 (8 -11). To date, five selenium-dependent GPx isoenzymes have been identified in humans: GPx1 and GPx2 are highly expressed in the intestinal epithelium, havi...

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Variation in the Selenoenzyme Genes and Risk of Advanced Distal Colorectal Adenoma

Cited by 105 publications

References 71 publications

Polymorphisms in the selenoprotein S and 15-kDa selenoprotein genes are associated with altered susceptibility to colorectal cancer

Polymorphisms in the selenoprotein S and 15-kDa selenoprotein genes are associated with altered susceptibility to colorectal cancer

Epidemiology and Polymorphisms Related to Bladder Cancer in Ecuadorian Individuals

Induction of Glutathione Peroxidase 4 Expression during Enterocytic Cell Differentiation

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