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Entity | Breast cancer |
Disease | Hu et al. (2001) found statistically significant difference in SEP15 allelic distribution for rs5859 between breast cancer individuals (DNA obtained from tumours, n=60) and cancer-free individuals (DNA obtained from lymphocytes, n=490) among African Americans. Studies conducted by Nasr et al. (2003) also suggest possible role of SEP15 in breast cancer development among African American women. The authors used four highly polymorphic microsatellite markers on the chromosome 1 region that includes SEP15 gene, to assess the difference in heterozygosity index at studied loci between DNA obtained from breast cancer tumours (n=61) and DNA obtained from lymphocytes of cancer-free individuals (n=50). Significant reduction of heterozygosity was found for locus that was most tightly linked to SEP15 gene. |
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Entity | Head and neck cancer |
Disease | Hu et al. (2001) found statistically significant difference in SEP15 allelic distribution for rs5859 between head and neck cancer individuals (DNA obtained from tumours, n=33) and cancer-free individuals (DNA obtained from lymphocytes, n=490) among African Americans. |
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Entity | Mesothelioma |
Disease | Apostolou et al. (2004) reported that SEP15 gene expression was downregulated in malignant mesothelioma (MM) cell lines (14 out of 23 cell lines examined) and mesothelioma tumours (3 out of 5 tissue specimens examined). The authors examined also the effect of selenium in MM cell lines on the growth inhibition and apoptosis. They observed that suppression of SEP15 expression by siRNA affected the response of cells to selenium, making them more resistant to the microelement. The growth inhibition and apoptosis effects followed by selenium treatment were also less pronounced in cells with variant alleles of SEP15 (SEP15 1125A, rs5859) as compared to cells with wild type allele (SEP15 1125G). |
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Entity | Lung cancer |
Disease | In the case control study (238 cases, 340 controls), Jablonska et al. (2008) observed a modifying effect of SEP15 polymorphism (rs5859) on lung cancer risk associated with selenium status. The high risk of lung cancer in the studied group was associated with low as well as with high plasma selenium concentration. After stratifying the data according to SEP15 genotype, it was found that among individuals with high selenium status, the risk of lung cancer was increased among those possessing at least one wild type allele, whereas in those with both variant alleles, the risk was decreased (figure 2). No expression change for SEP15 was observed between malignant and non-malignant lung tissue (study of 33 non-small cell lung cancer patients, conducted by Gresner et al., 2009). |
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| Figure 2. Joint effect of plasma selenium concentration and SEP15 1125G/A polymorphism for lung cancer development. OR - Odds Ratio for lung cancer risk. SEP15 genotypes: 1125GG (black line), 1125GA (yellow line), 1125AA (red line). Test for trends in SEP15 genotypes: p=0.038 for GG, p=0.035 for GA, p=0.030 for AA. Test for trend differences: AA vs. GG: p=0.049, AA vs. GA: p=0.025 (results of this study were published in Jablonska et al., 2008). |
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Entity | Bladder cancer |
Disease | Reszka et al. (2009) indicated that SEP15 was down expressed in the blood leucocytes of bladder cancer patients (33 males) as compared to healthy controls (47 males). SEP15 expression was positively correlated with tumour grade. |
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Entity | Prostate cancer |
Disease | Penney et al. (2010) conducted nested case control study among 1286 cases and 1267 controls to assess the relationship between five SEP15 polymorphisms (rs5859, rs479341, rs561104, rs527281, rs1407131), selenium status and prostate cancer risk and survival. Authors did not found any association between SEP15 polymorphisms and prostate cancer risk. However they observed that three variants (rs479341, rs1407131 and rs561104) were significantly associated with prostate cancer mortality and and one of the SNPs (rs561104) was shown to modify prostate cancer survival in association with selenium status. |
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Entity | Colon/colorectal cancer |
Disease | Studies conducted in mice by Irons et al. (2010), showed that down regulation of SEP15 inhibited colon cancer development induced by injection of mouse CT26 colon cancer cells. Authors suggest that targeted down regulation of SEP15 in colon cancer cells may protect them from tumorigenesis. Meplan et al. (2010) conducted case control study including 832 cases and 705 controls, in which they assessed the association between colorectal cancer and several SNPs within genes encoding selenoproteins and also other proteins. They found significant two-loci interaction between SEP15 (rs5859) and other selenoprotein (Sepp1) associated with colon cancer risk. In a similar study, involving 827 cases and 733 controls, Sutherland et al. (2010) found two SNPs within SEP15 (rs5845 and rs5859) to be associated with colorectal cancer risk. |
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