https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 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:26195 Wed 11 Apr 2018 15:00:42 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19379 Wed 11 Apr 2018 14:19:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28231 Wed 01 Aug 2018 14:52:20 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:20582 Sat 24 Mar 2018 07:55:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5128 T and N2792S, 8375A>G) to be associated with an allele dose–dependent increase in risk of familial breast cancer in a German population. We extended the analysis of AKAP9 M463I, which is in strong linkage disequilibrium with AKAP9 N2792S, to 9523 breast cancer patients and 13 770 healthy control subjects from seven independent European and Australian breast cancer studies. All statistical tests were two-sided. The collaborative analysis confirmed the association of M463I with increased breast cancer risk. Among all breast cancer patients, the combined adjusted odds ratio (OR) of breast cancer for individuals homozygous for the rare allele TT (frequency = 0.19) compared with GG homozygotes was 1.17 (95% confidence interval [CI] = 1.08 to 1.27, P = .0003), and the OR for TT homozygotes plus GT heterozygotes compared with GG homozygotes was 1.10 (95% CI = 1.04 to 1.17, P = .001). Among the combined subset of 2795 familial breast cancer patients, the respective ORs were 1.27 (95% CI = 1.12 to 1.45, P = .0003) and 1.16 (95% CI = 1.06 to 1.27, P = .001).]]> Sat 24 Mar 2018 07:48:55 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:45355 loss-of-function (LoF) variants in the base excision repair (BER) gene NTHL1 cause a high-risk hereditary multi-tumor syndrome that includes breast cancer, but the contribution of heterozygous variants to hereditary breast cancer is unknown. An analysis of 4985 women with breast cancer, enriched for familial features, and 4786 cancer-free women revealed significant enrichment for NTHL1 LoF variants. Immunohistochemistry confirmed reduced NTHL1 expression in tumors from heterozygous carriers but the NTHL1 bi-allelic loss characteristic mutational signature (SBS 30) was not present. The analysis was extended to 27,421 breast cancer cases and 19,759 controls from 10 international studies revealing 138 cases and 93 controls with a heterozygous LoF variant (OR 1.06, 95% CI: 0.82-1.39) and 316 cases and 179 controls with a missense variant (OR 1.31, 95% CI: 1.09-1.57). Missense variants selected for deleterious features by a number of in silico bioinformatic prediction tools or located within the endonuclease III functional domain showed a stronger association with breast cancer. Somatic sequencing of breast cancers from carriers indicated that the risk associated with NTHL1 appears to operate through haploinsufficiency, consistent with other described low-penetrance breast cancer genes. Data from this very large international multicenter study suggests that heterozygous pathogenic germline coding variants in NTHL1 may be associated with low- to moderate- increased risk of breast cancer.]]> Mon 01 May 2023 14:42:02 AEST ]]>