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

Abstract

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.

The effects of interactions between selenium and zinc serum concentration and SEP15 and SLC30A3 gene polymorphisms on memory scores in a population of mature and elderly adults

“…Indeed, minor allelic variants of SEP15 rs5845 have been shown to have functional consequences. These SNPs have been reported to affect breast cancer risk (Hu et al 2001) and the risk of lung cancer in smokers (Jablonska et al 2008) and also to influence the risk of rectal cancer in men (Sutherland et al 2010). It is important highlight that these studies cited also serve to illustrate the absence of neurobiological studies for SEP15 gene.…”

The Role of Selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities

“…Related to this finding, polymorphisms in the SELS gene as well as the gene encoding another ER selenoprotein, SEP15, were recently correlated to increased risk for colorectal cancer (247). SELS has been shown to be a glucose-regulated protein involved in the retrotranslocation of misfolded proteins from the ER into the cytosol for proteasomal degradation (80,128).…”

Selenoproteins: Molecular Pathways and Physiological Roles

“…Genetic variants in the SelS gene were shown to regulate the circulating levels of proinflamatory cytokines including IL-6, IL-1␤, and TNF-␣ (72) and have been linked to the development of coronary heart disease, ischemic stroke (4), preeclampsia (261), gastric (315) and colorectal (337) cancer, and other conditions that are associated with increased inflammation. Moreover, characterization of the recently developed SelK knockout mouse model demonstrated that SelK deficiency leads to deficient Ca 2ϩ flux during immune cell activation and impaired immune response (358).…”