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

Cited 70 time in Web of Science Cited 83 time in Scopus
Authors
Sutherland, Alison; Kim, Dong-Hyun; Relton, Caroline; Ahn, Yoon-Ok; Hesketh, John
Issue Date
2010-09
Publisher
SPRINGER
Citation
GENES AND NUTRITION; Vol.5 3; 215-223
Keywords
SeleniumRectal cancer15-kDa selenoproteinSelenoprotein SSNP
Abstract
Selenium (Se), a dietary trace metal essential for human health, is incorporated into similar to 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.
ISSN
1555-8932
Language
English
URI
https://hdl.handle.net/10371/76880
DOI
https://doi.org/10.1007/s12263-010-0176-8
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College of Medicine/School of Medicine (의과대학/대학원)Preventive Medicine (예방의학전공)Journal Papers (저널논문_예방의학전공)
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