Rabbit Anti-Human XRCC6 (Phospho-Ser5) polyclonal antibody

Environmental risk factors cause DNA damages. Imprecise DNA repair leads to chromosome aberrations, genome destabilization and hepatocarcinogenesis. Ku is a key DNA double-strand break repair protein. We hypothesized that the genetic variants in Ku subunits encoding genes, XRCC5/XRCC6, may contribute to hepatocellular carcinoma (HCC) susceptibility. We genotyped 13 common single nucleotide polymorphisms (SNPs) in XRCC5 and XRCC6 and evaluated their associations with HCC risk in 689 pathologically confirmed cases and 690 cancer-free controls from a Chinese population. We found that a significantly reduced risk for HCC was associated with XRCC5 rs16855458 [odds ratio (OR) = 0.59; 95% confidence interval (CI) = 0.43-0.81; CA + AA versus CC] and a significantly increased risk for HCC was associated with XRCC5 rs9288516 (OR = 2.02; 95% CI = 1.42-2.86; TA + AA versus TT) even after Bonferroni correction (P-corrected = 0.026 and 0.002, respectively). The effects of rs16855458 (OR = 0.57; 95% CI = 0.37-0.86, P = 0.008) and rs9288516 (OR = 1.86; 95% CI = 1.19-2.90, P = 0.007) were more significant in hepatitis B surface antigen-infected subjects than non-infected subjects. The haplotype-based analysis revealed that in XRCC5, AA in block 1 (OR = 0.63; 95% CI = 0.48-0.83) and CGGTT in block 2 (OR = 0.52; 95% CI = 0.39-0.69) were associated with decreased HCC risk (P-corrected = 0.013 and < 0.001, respectively). The aforementioned two SNPs exhibited a significant cumulative risk effect (P-trend < 0.001). Additionally, potential interaction among XRCC5 rs9288516 and rs2267437, rs5751131 in XRCC6 was indicated by the multifactor dimensionality reduction analysis. In conclusion, XRCC5 variants may play a role in determining individual's HCC susceptibility, which warranted validation in larger studies.

Cancers arise by the gradual accumulation of mutations in multiple genes. We now use shotgun pyrosequencing to characterize RNA mutations and expression levels unique to malignant pleural mesotheliomas (MPMs) and not present in control tissues. On average, 266 Mb of cDNA were sequenced from each of four MPMs, from a control pulmonary adenocarcinoma (ADCA), and from normal lung tissue. Previously observed differences in MPM RNA expression levels were confirmed. Point mutations were identified by using criteria that require the presence of the mutation in at least four reads and in both cDNA strands and the absence of the mutation from sequence databases, normal adjacent tissues, and other controls. In the four MPMs, 15 nonsynonymous mutations were discovered: 7 were point mutations, 3 were deletions, 4 were exclusively expressed as a consequence of imputed epigenetic silencing, and 1 was putatively expressed as a consequence of RNA editing. Notably, each MPM had a different mutation profile, and no mutated gene was previously implicated in MPM. Of the seven point mutations, three were observed in at least one tumor from 49 other MPM patients. The mutations were in genes that could be causally related to cancer and included XRCC6, PDZK1IP1, ACTR1A, and AVEN.