https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20989 Wed 11 Apr 2018 11:20:08 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28088 −6 to P = 7.7 × 10⁻⁵). Only one falls into a haplotype previously associated with other cancer types (rs7705526, in TERT intron 1), and this SNP has been shown to alter TERT promoter activity. One of the novel associations (rs13174814) maps to a second region in the TERT promoter and the other (rs62329728) is in the promoter region of CLPTM1L; neither are correlated with previously reported cancer-associated SNPs. Using TCGA RNASeq data, we found significantly increased expression of both TERT and CLPTM1L in endometrial cancer tissue compared with normal tissue (TERTP = 1.5 × 10⁻¹⁸, CLPTM1LP = 1.5 × 10⁻¹⁹). Our study thus reports a novel endometrial cancer risk locus and expands the spectrum of cancer types associated with genetic variation at 5p15, further highlighting the importance of this region for cancer susceptibility.]]> Tue 10 Oct 2023 08:38:44 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7340 Sat 24 Mar 2018 08:35:13 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26944 0.05), but cases presented with an excess of rare germline deletions overlapping likely functional genomic regions including genes (P = 8 x 10^-10), CpG islands (P = 1 x 10^-7) and sno/miRNAs regions (P = 3 x 10^-9). On average, at least one additional gene and two additional CpG islands were disrupted by rare deletions in cases compared to controls. The most pronounced difference was that over 30 sno/miRNAs were disrupted by rare deletions in cases for every single disruption event in controls. A total of 13 DNA repair genes were disrupted by rare deletions in 19/1,209 cases (1.6 %) compared to one gene in 1/528 controls (0.2 %; P = 0.007), and this increased DNA repair gene loss in cases persisted after excluding five individuals carrying CNVs disrupting mismatch repair genes MLH1, MSH2 and MSH6 (P = 0.03). There were 34 miRNA regions deleted in at least one case but not in controls, the most frequent of which encompassed hsa-mir-661 and hsa-mir-203. Our study implicates rare germline deletions of functional and regulatory regions as possible mechanisms conferring endometrial cancer risk, and has identified specific regulatory elements as candidates for further investigation.]]> Sat 24 Mar 2018 07:27:02 AEDT ]]>