https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24073 -11). SNP rs727479 was also among those most strongly associated with circulating E₂ concentrations in 2767 post-menopausal controls (P=7.4x10^-8). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11-1.21) is compatible with that predicted by the observed effect on E₂ concentrations (1.09, CI=1.03-1.21), consistent with the hypothesis that endometrial cancer risk is driven by E₂. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (P_interaction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction.]]> Wed 19 Apr 2023 16:42:45 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30306 Wed 15 Dec 2021 16:09:28 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27984 Wed 15 Dec 2021 16:06:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30271 Tue 13 Aug 2024 11:16:49 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20561 Tue 10 Oct 2023 08:38:59 AEDT ]]> 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.]]> Thu 08 Aug 2024 15:35:23 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17125 −10) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes.]]> Sat 24 Mar 2018 08:02:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26799 Sat 24 Mar 2018 07:36:26 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27532 Sat 24 Mar 2018 07:28:58 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 ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27911 −8) at 6p22.3 (rs1740828; P = 2.29 x 10⁻⁸, OR = 1.20), providing evidence of an additional region of interest for genetic susceptibility to endometrial cancer.]]> Sat 24 Mar 2018 07:24:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47283 Fri 13 Jan 2023 10:24:53 AEDT ]]>