Abstract：
BACKGROUND: Selenium manifests its biological effects through its incorporation into selenoproteins, which play several roles in countering oxidative and inflammatory responses implicated in colorectal carcinogenesis. Selenoprotein genetic variants may contribute to colorectal cancer (CRC) development, as we previously observed for SNP variants in a large European prospective study and a Czech case-control cohort.
METHODS: We tested if significantly associated selenoprotein gene SNPs from these studies were also associated with CRC risk in case-control studies from Ireland (colorectal neoplasia, i.e., cancer and adenoma cases: 450, controls: 461) and the Czech Republic (CRC cases: 718, controls: 646). Genotyping of 23 SNPs (20 in the Irish and 13 in the Czechs) was performed by competitive specific allele-specific PCR (KASPar). Multivariable adjusted logistic regression was used to assess the associations with CRC development.
RESULTS: We found significant associations with an increased CRC risk for rs5859 (SELENOF) and rs2972994 (SELENOP) in the Irish cohort but only with rs4802034 (SELENOV) in the Czechs. Significant associations were observed for rs5859 (SELENOF), rs4659382 (SELENON), rs2972994 (SELENOP), rs34713741 (SELENOS), and the related Se metabolism gene variant rs2275129 (SEPHS1) with advanced colorectal neoplasia development. However, none of these findings retained significance after multiple testing corrections.
CONCLUSIONS: Several SNPs previously associated with CRC risk were also associated with CRC or colorectal neoplasia development in either the Irish or Czech cohorts. Selenoprotein gene variation may modify CRC risk across diverse European populations, although the specific variants may differ.
METHODS: We tested if significantly associated selenoprotein gene SNPs from these studies were also associated with CRC risk in case-control studies from Ireland (colorectal neoplasia, i.e., cancer and adenoma cases: 450, controls: 461) and the Czech Republic (CRC cases: 718, controls: 646). Genotyping of 23 SNPs (20 in the Irish and 13 in the Czechs) was performed by competitive specific allele-specific PCR (KASPar). Multivariable adjusted logistic regression was used to assess the associations with CRC development.
RESULTS: We found significant associations with an increased CRC risk for rs5859 (SELENOF) and rs2972994 (SELENOP) in the Irish cohort but only with rs4802034 (SELENOV) in the Czechs. Significant associations were observed for rs5859 (SELENOF), rs4659382 (SELENON), rs2972994 (SELENOP), rs34713741 (SELENOS), and the related Se metabolism gene variant rs2275129 (SEPHS1) with advanced colorectal neoplasia development. However, none of these findings retained significance after multiple testing corrections.
CONCLUSIONS: Several SNPs previously associated with CRC risk were also associated with CRC or colorectal neoplasia development in either the Irish or Czech cohorts. Selenoprotein gene variation may modify CRC risk across diverse European populations, although the specific variants may differ.
摘要：
背景：硒通过掺入硒蛋白来表现其生物学效应，在抵抗与结直肠癌发生有关的氧化和炎症反应中起着多种作用。硒蛋白遗传变异可能有助于结直肠癌（CRC）的发展，正如我们之前在大型欧洲前瞻性研究和捷克病例对照队列中观察到的SNP变异。
方法：在来自爱尔兰的病例对照研究中，我们测试了来自这些研究的显着相关的硒蛋白基因SNP是否也与CRC风险相关（结直肠肿瘤，即，癌症和腺瘤病例：450例，对照：461例）和捷克共和国（CRC病例：718例，对照：646例）。通过竞争性特异性等位基因特异性PCR（KASPar）对23个SNP（爱尔兰人20个，捷克人13个）进行基因分型。使用多变量调整逻辑回归来评估与CRC发展的关联。
结果：我们发现在爱尔兰队列中rs5859(SELENOF)和rs2972994(SELENOP)与CRC风险增加显著相关，但在捷克队列中只有rs4802034(SELENOV)。观察到rs5859（SELENOF）的显着关联，rs4659382(SELENON),rs2972994(SELENOP),rs34713741(SELENOS),和与晚期结直肠肿瘤发展相关的Se代谢基因变异体rs2275129(SEPHS1)。然而,经过多次测试校正后，这些发现均未保留显著性。
结论：在爱尔兰或捷克队列中，先前与CRC风险相关的一些SNP也与CRC或结直肠肿瘤的发展相关。硒蛋白基因变异可能会改变不同欧洲人群的CRC风险，尽管具体的变体可能不同。
方法：在来自爱尔兰的病例对照研究中，我们测试了来自这些研究的显着相关的硒蛋白基因SNP是否也与CRC风险相关（结直肠肿瘤，即，癌症和腺瘤病例：450例，对照：461例）和捷克共和国（CRC病例：718例，对照：646例）。通过竞争性特异性等位基因特异性PCR（KASPar）对23个SNP（爱尔兰人20个，捷克人13个）进行基因分型。使用多变量调整逻辑回归来评估与CRC发展的关联。
结果：我们发现在爱尔兰队列中rs5859(SELENOF)和rs2972994(SELENOP)与CRC风险增加显著相关，但在捷克队列中只有rs4802034(SELENOV)。观察到rs5859（SELENOF）的显着关联，rs4659382(SELENON),rs2972994(SELENOP),rs34713741(SELENOS),和与晚期结直肠肿瘤发展相关的Se代谢基因变异体rs2275129(SEPHS1)。然而,经过多次测试校正后，这些发现均未保留显著性。
结论：在爱尔兰或捷克队列中，先前与CRC风险相关的一些SNP也与CRC或结直肠肿瘤的发展相关。硒蛋白基因变异可能会改变不同欧洲人群的CRC风险，尽管具体的变体可能不同。
