Rs1050631

rs1050631 is a SNP on chromosome 18q12 in exon 6 of SLC39A6 gene, associated with length of survival in esophageal squamous-cell carcinoma(ESCC). The SNP is located in the 5&#8217; UTR of SLC39A6. In a study, a genome-wide scan of SNPs to identify variants associated with length of survival in 1331 individuals with ESCC was performed, and was validated by two independent sets, including 1962 individuals with ESCC (1308 and 654 individuals in two different replications). The hazard ratio for death (odds ratio) (T; T) and (C; T) from ESCC in the 1331 test cases was 1.34 (95% confidence interval (CI) = 1.17&#8722;1.53; P = 7.78 E-6). For the combined data, hazard ratio of death similarly was found to be 1.34 (95% CI = 1.17&#8722;1.53; P = 7.78 E&#8722;6). The combined discovery and replication sets for analysis showed that the Mean Survival Times (MSTs) for individuals with the TT or CT genotype at rs1050631 were 17 and 25 months, respectively, substantially less than the 32 months seen for individuals with the CC genotype.

When a fine mapping of a 600-kb region of SLC39A6 centered on rs1050631 was performed, the study was able to test 866 SNPs and identified another 24 imputed SNPs in the SLC39A6 gene and its potential promoter region highly correlated with length of survival in person with ESCC. 7 of these SNPs, located in the 5&#8217; UTR were in high LD with the rs1050631 SNP, and it was also shown that these SNPs could be tagged by rs7242481. Since, both of these tagging SNPs &#8211; rs7242481 and rs7242481&#8212; showed relation to the mean survival time (MST) of ECSS patients, conditional study was performed to see the interdependence between the two SNPs. The result showed that after conditional analysis, both SNPs were no longer significant, indicating they are unlikely to represent independent signals.

rs7242481, located in the 5&#8242; UTR of SLC39A6, disturbs a transcriptional repressor binding site and results in upregulation of SLC39A6 expression. An experiment was performed to verify overexpression of SLC39A6, in which of 76 primary ESCC tissues, 55 (72.4%) overexpressed SLC39A6 mRNA, with the mean expression level (&#177; s.e.m.) being significantly higher in ESCC tumors than in their corresponding adjacent normal tissues (0.01403 &#177; 0.0023 versus 0.0062 &#177; 0.0008; P = 0.0022). The study showed that a G>A transition at rs724248, which is located in the 5&#8242;&#61472;UTR of the gene, causes increased, constitutive expression of SLC39A6, probably owing to the disturbance of a transcriptional repressor binding site, suggesting the functional relevance of this site.

The C>T transition at rs1050631 showed synonymous change located in exon 6 of SLC39A6. However, further studies are warranted to elucidate whether the C>T change at rs1050631 affects SLC39A6 function. 

Cancer