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
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DOI：
10.1007/s12263-010-0176-8
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发表时间：
2010-09-01
影响因子：
3.5
通讯作者：
Hesketh, John
中科院分区：
文献类型：
--
作者：
Sutherland, Alison;Kim, Dong-Hyun;Hesketh, John
硒（Se）是人体健康所必需的一种微量元素，它被整合到25种硒蛋白中，包括硒蛋白S（SelS）和15-kDa硒蛋白（Sep 15），这两种硒蛋白都参与内质网蛋白的解折叠反应。这项研究的目的是调查是否在这些硒蛋白基因的遗传变异与结肠直肠癌（CRC）的风险改变。采用Sequenom技术对韩国827例CRC患者和733例健康对照进行了硒蛋白基因7个SNP和锰超氧化物歧化酶编码基因1个SNP的基因分型。多变量logistic回归分析显示，调整生活方式因素后，三种SNP变异与疾病风险改变相关。在SELS中，女性rs34713741纯合子TT的平均比值比为2.25 [95%CI 1.13，4.48]，T变异与直肠癌的高风险相关，比值比分别为2.47和2.51，在SEP 15中，rs 5845和rs 5859的次要A和T等位基因与男性直肠癌风险增加相关。数据表明，rs 5845、rs 5859和rs34713741的次要等位基因与直肠癌风险增加相关，并且这三个SNP的影响取决于性别。结果突出了硒，参与蛋白质解折叠反应和CRC风险的两种硒蛋白的功能之间的潜在联系。需要进一步的研究来调查变异体对CRC风险的影响是否也受到膳食硒摄入量的调节。
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.