https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51411 Wed 28 Feb 2024 15:41:09 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50960 Wed 28 Feb 2024 15:22:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45194 n = 294, 95–106 years; controls: n = 1105, 55–65 years) by assessing their polygenic risk scores (PRS) based on a genome wide association study (GWAS) threshold of p < 5 x 10⁻⁵. PRS were constructed using GWAS summary data from two exceptional longevity (EL) analyses and eight cardiovascular-related risk factors (lipids) and disease (myocardial infarction, coronary artery disease, stroke) analyses. A higher genetic risk for exceptional longevity (EL) was significantly associated with longevity in our sample (odds ratio (OR) = 1.19–1.20, p = 0.00804 and 0.00758, respectively). Two cardiovascular health PRS were nominally significant with longevity (HDL cholesterol, triglycerides), with higher PRS associated with EL, but these relationships did not survive correction for multiple testing. In conclusion, ELL individuals did not have significantly lower polygenic risk for the majority of the investigated cardiovascular health traits. Future work in larger cohorts is required to further explore the role of cardiovascular-related genetic variants in EL.]]> Wed 26 Oct 2022 14:27:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44984 CDKN2A-variants. A replication study using a set of 1,200 melanoma patient DNA samples and similarly large series of healthy controls was undertaken. Results: We selected 21 potentially deleterious variants in 20 genes (VRK1, MYCT1, DNAH14, CASC3, MS4A12, PRC1, WWOX, CARD6, EXO5, CASC3, CASP8AP2, STK33, SAMD11, CNDP2, CPNE1, EFCAB6, CABLES1, LEKR1, NUDT17, and RRP15), which were identified by WES and confirmed by Sanger sequencing for an association study. Evaluation of the allele distribution among carriers and their relatives in available family trios revealed that these variants were unlikely to account for many familial cases of melanoma. Replication study revealed no statistically significant differences between cases and controls. Conclusion: Although most of the changes seemed to be neutral we could not exclude an association between variants in VRK1, CREB3L3, EXO5, and STK33 with melanoma risk.]]> Wed 26 Oct 2022 09:22:11 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47731 g| ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.]]> Wed 25 Jan 2023 14:39:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42460 FTO) single-nucleotide polymorphism (SNP) rs9939609 is a major SNP associated with obesity and has been used as an instrumental variable for obesity in a Mendelian randomization (MR) approach. An interaction between the FTO SNP and macronutrient intake for obesity was suggested previously. Objective: The aim of this study was to assess the associations between obesity and cataract, using FTO SNP rs9939609 as an instrumental variable in an MR approach, and explore interactions of this SNP with macronutrient intake in relation to risk of cataract in a population-based cohort. Methods: The Blue Mountains Eye Study (BMES) is a longitudinal population-based study of common eye disease. Of 3654 baseline participants of the BMES (1992-1994), 2334 (75.8% of survivors) and 1952 (76.7% of survivors) were followed 5 and 10 y later. During the 5-y follow-up, 1174 new participants were examined. Cumulative cataract was defined as the presence of cortical, nuclear, or posterior subcapsular (PSC) cataract at any visit, following the Wisconsin Cataract Grading System. Imputed dosage of the FTO SNP rs9939609 was used. Quintiles of macronutrient intake (carbohydrates, protein, fats) were derived from an FFQ. ORs and 95% CIs were estimated using multivariable-adjusted logistic regression models. Results: After multivariable adjustment, there were no associations between BMI and any cataract types in MR models using rs9939609 as an instrumental variable. However, an interaction between rs9939609 and protein intake for PSC cataract risk was suggested (P = 0.03). In analyses stratified by quintiles of protein intake, each minor allele of rs9939609 was associated with increased odds of PSC (OR: 2.14; 95% CI: 1.27, 3.60) in the lowest quintile subgroup only. Conclusions: Obesity was not causally associated with age-related cataract. However, among persons in the lowest quintile of protein intake, obesity may be associated with PSC cataract.]]> Wed 24 Aug 2022 11:18:26 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38878 n = 13) erythrocyte-derived (CD235a) extracellular particles were increased, while platelet-derived (CD41b), leukocyte-derived (CD45), and CD4⁺T cell-derived (CD4) extracellular particles were decreased compared to both healthy controls (n = 27) (p<0.05) and secondary progressive multiple sclerosis patients (n = 9) (p < 0.05). Endothelium-derived extracellular particles (CD146) were increased in stable relapsing-remitting multiple sclerosis patients (n = 17) compared to healthy controls (p < 0.05). Extracellular particles from several different cells of origin correlated with each other and clinical parameters (e.g. disease duration, number of relapses, EDSS), though clinical correlations did not withstand corrections for multiple comparisons. Conclusions: Concentrations of erythrocyte-, leukocyte-, and platelet-derived extracellular particles were altered in relapsing multiple sclerosis patients and endothelium-derived extracellular particles were increased in stable relapsing-remitting patients compared to healthy controls. Extracellular particles may provide insights into altered the crosstalk between peripheral blood cells in multiple sclerosis, which may lead to the discovery of novel therapeutic targets.]]> Wed 23 Feb 2022 11:05:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53345 Wed 22 Nov 2023 10:19:25 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42701 Wed 22 Mar 2023 15:07:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42676 Wed 22 Mar 2023 14:34:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48596 Wed 22 Mar 2023 08:46:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37060 69 µg/L, reference). The 80 months crude survival after diagnosis was 79.5% (95% CI: 68.5-92.4%) for individuals in the highest tertile and 58.1% (95% CI: 45.1-74.9%) for individuals in the lowest tertile with stage I lung cancer. Conclusion: These results suggest that in patients undergoing treatment for stage I lung cancer, serum selenium levels at the time of diagnosis (>69 µg/L) may be associated with improved overall survival.]]> Wed 19 Jan 2022 15:19:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36834 Wed 17 Nov 2021 16:29:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36471 Wed 17 Nov 2021 16:29:19 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37757 ARF in human and p19^ARF in mouse) that binds to and inhibits mouse double minute 2 homolog (MDM2) leading to p53 activation, whereas p53 suppresses c-Myc through a combination of mechanisms involving transcriptional inactivation and microRNA-mediated repression. Nonetheless, the regulatory interactions between c-Myc and p53 are not retained by cancer cells as is evident from the often-imbalanced expression of c-Myc over wildtype p53. Although p53 repression in cancer cells is frequently associated with the loss of ARF, we disclose here an alternate mechanism whereby c-Myc inactivates p53 through the actions of the c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP). MILIP functions to promote p53 polyubiquitination and turnover by reducing p53 SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2). MILIP upregulation is observed amongst diverse cancer types and is shown to support cell survival, division and tumourigenicity. Thus our results uncover an inhibitory axis targeting p53 through a pan-cancer expressed RNA accomplice that links c-Myc to suppression of p53.]]> Wed 17 Nov 2021 16:28:34 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37273 MSH3, PMS1, MLH3, EXO1, POLD1, POLD3 RFC1, RFC2, RFC3, RFC4, RFC5, PCNA, LIG1, RPA1, RPA2, RPA3, POLD2, POLD4, MLH1, MSH2, MSH6, and PMS2) in 274 LLS patients. Detected variants were annotated and filtered using ANNOVAR and FILTUS software. Results: Thirteen variants were revealed in MLH1, MSH2, and MSH6, all genes previously linked to LS. Five additional genes (EXO1, POLD1, RFC1, RPA1, and MLH3) were found to harbor 11 variants of unknown significance in our sample cohort, two of them being frameshift variants. Conclusion: We have shown that other genes associated with the process of DNA MMR have a high probability of being associated with LLS families. These findings indicate that the spectrum of genes that should be tested when considering an entity like Lynch‐like syndrome should be expanded so that a more inclusive definition of this entity can be developed.]]> Wed 17 Nov 2021 16:28:09 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37272 Wed 16 Sep 2020 14:03:32 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49893 A and I157T. Predictors of survival were determined among CHEK2 pathogenic variant carriers using the Cox proportional hazards model. The median follow-up was 17.5 years. Covariates included age (≤60; >61 years), sex (female; male), clinical characteristics (stage: TNM, grade, histopathological type), smoking status (non-smoking; smoking) and cancer family history (negative; positive). Results: We found no impact of CHEK2 mutations on bladder or kidney cancer survival. However, we observed a possible increased survival in the subgroup of patients with stage T1 bladder cancer with CHEK2 mutations but this did not meet statistical significance (HR = 0.14; 95% CI 0.02–1.04; p = 0.055). Moreover, we observed that the missense mutations were more frequent in the low grade invasive bladder cancer patient group (OR = 7.9; 95% CI 1.50–42.1; p = 0.04) and in patients with bladder cancer with stage Ta (OR = 2.4; 95% CI 1.30–4.55; p = 0.006). The different results where missense mutations occurs less often we observed among patients with high grade invasive bladder cancer (OR = 0.12; 95% CI 0.02–0.66; p = 0.04) and those with stage T1 disease (OR = 0.2; 95% CI 0.07–0.76; p = 0.01). Our investigations revealed that any mutation in CHEK2 occurs more often among patients with stage Ta bladder cancer (OR = 2.0; 95% CI 1.19–3.47; p = 0.01) and less often in patients with stage T1 disease (OR = 0.31; 95% CI 0.12–0.78; p = 0.01). In the kidney cancer patients, truncating mutations were present more often in the group with clear cell carcinoma GII (OR = 8.0; 95% CI 0.95–67.7; p = 0.05). The 10-year survival for all CHEK2 mutation carriers with bladder cancer was 33% and for non-carriers 11% (p = 0.15). The 10-year survival for CHEK2 mutation carriers with kidney cancer 34% and for non-carriers 20% (p = 0.5). Conclusion: CHEK2 mutations were not associated with any change in bladder or kidney cancer survival regardless of their age, sex, smoking status and family history. We observed a potentially protective effect of CHEK2 mutations on survival for patients with stage T1 bladder cancer. CHEK2 missense mutations were more common among patients with low grade invasive bladder cancer and in patients with stage Ta diease. The frequencies of the I157T CHEK2 pathogenic variant were less in patients with high grade invasive bladder cancer and those with stage T1 disease. Among patients with bladder cancer with stage Ta disease, the OR for any mutation in CHEK2 was 2.0 but for those with stage T1 disease, the OR was 0.3. We observed truncating CHEK2 mutations were associated with kidney cancer patients with GII clear cell carcinoma.]]> Wed 14 Jun 2023 17:10:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54801 Wed 13 Mar 2024 11:41:50 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49864 0.1 μg/L were correlated with 73% (52/71) of lung cancers diagnosed with stage I disease. Our findings support the role of chromium and the influence of key proteins on lung cancer burden in the general population.]]> Wed 07 Jun 2023 14:09:37 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55024 Wed 03 Apr 2024 15:41:54 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52322 Wed 03 Apr 2024 15:14:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47795 Tue 31 Jan 2023 15:32:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50431 Tue 25 Jul 2023 19:01:27 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53302  0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p = 2.56 × 10–9). Gene-based analyses identified novel genome-wide significant associations with PPP6C and FURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.]]> Tue 21 Nov 2023 12:03:34 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53291 Tue 21 Nov 2023 11:48:09 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41408 Tue 21 Mar 2023 18:03:04 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54378 Tue 20 Feb 2024 20:24:50 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54341 Tue 20 Feb 2024 16:12:28 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46467 P < 5 × 10⁻⁸) were identified as instrumental variables, and assessed using genome-wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non-endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non-endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non-endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non-endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.]]> Tue 19 Sep 2023 15:34:26 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44626 Tue 18 Oct 2022 11:11:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52582 Tue 17 Oct 2023 15:55:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41878 Tue 16 Aug 2022 10:04:26 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46235 Tue 15 Nov 2022 08:51:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54564 Tue 14 May 2024 13:54:22 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48335 Tue 14 Mar 2023 17:16:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48284 0.5 (OR 3.95, 95% CI 1.40–12.01, p = 0.006). Sequencing of 21 tumours from 20 heterozygous and 1 homozygous carriers of nine candidate MS variants identified four cases with biallelic inactivation through loss of the wild-type allele, while six lost the variant allele and ten that remained heterozygous. Biallelic loss of the wild-type alleles corresponded strongly with ER- and TN breast tumours, high homologous recombination deficiency scores and mutational signature 3. Using this approach, the p.Gly264Ser variant, which was previously suspected to be pathogenic based on small case–control analyses and loss of activity in in vitro functional assays, was shown to be benign with similar prevalence in cases and controls and seven out of eight tumours showing no biallelic inactivation or characteristic mutational signature. Conversely, evaluation of case–control findings and tumour sequencing data identified p.Ile144Thr, p.Arg212His, p.Gln143Arg and p.Gly114Arg as variants warranting further investigation.]]> Tue 14 Mar 2023 11:29:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35898 Tue 14 Jan 2020 11:55:50 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43079 Tue 13 Sep 2022 12:12:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51614 Tue 12 Sep 2023 13:49:19 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47243 Tue 10 Jan 2023 15:12:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42894 Tue 06 Sep 2022 14:32:21 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43823 Tue 04 Oct 2022 11:04:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48599 Tue 04 Apr 2023 19:22:25 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33388 Tue 03 Sep 2019 17:54:11 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38090 telomerase reverse transcriptase (TERT) have been associated with a wide range of cancers, including colorectal cancer (CRC) in LS. We combined genotype data from 1881 LS patients, carrying pathogenic variants in MLH1, MSH2 or MSH6, for rs2075786 (G>A, intronic variant), 1207 LS patients for rs2736108 (C>T, upstream variant) and 1201 LS patients for rs7705526 (C>A, intronic variant). The risk of cancer was estimated by heterozygous/homozygous odds ratio (OR) with mixed-effects logistic regression to adjust for gene/gender/country of sample origin considering family identity. The AA genotype of SNP rs2075786 is associated with 85% higher odds at developing cancer compared to GG genotype in MSH2 pathogenic variant carriers (p = 0.0160). Kaplan–Meier analysis also shows an association for rs2075786; the AA allele for MSH2 variant carriers confers risk for earlier diagnosis of LS cancer (log-rank p = 0.0011). We report a polymorphism in TERT to be a possible modifier of disease risk in MSH2 pathogenic variant carriers. The rs2075786 SNP in TERT is associated with a differential risk of developing cancer for MSH2 pathogenic variant carriers. Use of this information has the potential to personalise screening protocols for LS patients.]]> Tue 03 Aug 2021 19:10:28 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36559 Thu 28 Oct 2021 13:03:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40665 Thu 28 Jul 2022 12:15:19 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45379 Thu 27 Oct 2022 15:58:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45361 BRCA1 and BRCA2, including the identification of new predisposing genes. A total of 11,511 non-BRCA familial BC cases and population-matched cancer-free female controls in the BEACCON study were investigated in two sequencing phases: 1303 candidate genes in up to 3892 cases and controls, followed by validation of 145 shortlisted genes in an additional 7619 subjects. The coding regions and exon–intron boundaries of all candidate genes and 14 previously proposed BC genes were sequenced using custom designed sequencing panels. Pedigree and pathology data were analysed to identify genotype-specific associations. The contribution of ATM, PALB2 and CHEK2 to BC predisposition was confirmed, but not RAD50 and NBN. An overall excess of loss-of-function (LoF) (OR 1.27, p = 9.05 × 10⁻⁹) and missense (OR 1.27, p = 3.96 × 10⁻⁷³) variants was observed in the cases for the 145 candidate genes. Leading candidates harbored LoF variants with observed ORs of 2–4 and individually accounted for no more than 0.79% of the cases. New genes proposed by this study include NTHL1, WRN, PARP2, CTH and CDK9. The new candidate BC predisposition genes identified in BEACCON indicate that much of the remaining genetic causes of high-risk BC families are due to genes in which pathogenic variants are both very rare and convey only low to moderate risk.]]> Thu 27 Oct 2022 15:32:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45363 Thu 27 Oct 2022 11:46:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44981 path_MMR) variant carriers, the incidence of colorectal cancer (CRC) was not reduced when colonoscopy was undertaken more frequently than once every 3 years, and that CRC stage and interval since last colonoscopy were not correlated. Methods: The Prospective Lynch Syndrome Database (PLSD) that records outcomes of surveillance was examined to determine survival after colon cancer in relation to the time since previous colonoscopy and pathological stage. Only path_MMR variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable) were included in the analysis. Results: Ninety-nine path_MMR carriers had no cancer prior to or at first colonoscopy, but subsequently developed colon cancer. Among these, 96 were 65 years of age or younger at diagnosis, and included 77 path_MLH1, 17 path_MSH2, and 2 path_MSH6 carriers. The number of cancers detected within < 1.5, 1.5–2.5, 2.5–3.5 and at > 3.5 years after previous colonoscopy were 9, 43, 31 and 13, respectively. Of these, 2, 8, 4 and 3 were stage III, respectively, and only one stage IV (interval 2.5–3.5 years) disease. Ten-year crude survival after colon cancer were 93, 94 and 82% for stage I, II and III disease, respectively (p < 0.001). Ten-year crude survival when the last colonoscopy had been < 1.5, 1.5–2.5, 2.5–3.5 or > 3.5 years before diagnosis, was 89, 90, 90 and 92%, respectively (p = 0.91). Conclusions: In path_MLH1 and path_MSH2 carriers, more advanced colon cancer stage was associated with poorer survival, whereas time since previous colonoscopy was not. Although the numbers are limited, together with our previously reported findings, these results may be in conflict with the view that follow-up of path_MMR variant carriers with colonoscopy intervals of less than 3 years provides significant benefit.]]> Thu 27 Oct 2022 09:15:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48845 Thu 20 Apr 2023 10:58:52 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54811 Thu 14 Mar 2024 14:24:56 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46914 Thu 08 Dec 2022 08:47:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46900 Thu 08 Dec 2022 08:09:19 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51479 Thu 07 Sep 2023 10:53:30 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35067 853.0–973.9 μg/l). Among five analyzed genetic variants, rs11568818 in MMP-7 appeared to be correlated with 2-fold increased prostate cancer risk (OR = 2.39, 95% CI = 1.19–4.82, p = 0.015). Conclusion: Our results suggest a significant correlation of higher serum zinc levels with the diagnosis of prostate cancer. The polymorphism rs11568818 in MMP-7 gene was also associated with an increased prostate cancer risk in Poland.]]> Thu 04 Nov 2021 10:38:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41461 TP53 vary depending on the subtype, such that ER-negative tumours have a high rate, and in ER-positive tumours they are less common. Previous studies have implicated the intronic polymorphism in TP53 (rs17878362; or PIN3) with an increased risk of developing breast cancer, although little has been discerned on its prevalence in different subtypes. In this study, we investigated the prevalence of the PIN3 genotype in the blood of cohorts with ER-positive and the ER-negative subtype TNBC, and assessed its association with outcome. Methods: We genotyped 656 TNBC and 648 ER-positive breast cancer patients, along with 436 controls, and compared the prevalence of polymorphism rs17878362 in these cohorts. Results: We found there to be no differences in the prevalence of the PIN3 genotype between the ER-positive and TNBC cohorts. Furthermore, no statistically significant difference was observed in the outcome of patients in either cohort with respect to their PIN3 genotype. Conclusions: Taken together, our results do not support an association of the PIN3 genotype with increased breast cancer risk, either in ER-positive or ER-negative patients.]]> Thu 01 Sep 2022 11:19:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44131 Sat 08 Oct 2022 12:36:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50640 Mon 31 Jul 2023 16:34:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47780 Mon 30 Jan 2023 10:58:57 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38391 Mon 29 Jan 2024 18:44:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38628 + T cells of relapsing–remitting (RR) MS patients compared to healthy controls and identified differentially methylated regions (DMRs) in HLA-DRB1 and RNF39. This study aimed to investigate the DNA methylation profiles of the CD4⁺ T cells of progressive MS patients. DNA methylation was measured in two separate case/control cohorts using the Illumina 450K/EPIC arrays and data was analysed with the Chip Analysis Methylation Pipeline (ChAMP). Single nucleotide polymorphisms (SNPs) were assessed using the Illumina Human OmniExpress24 arrays and analysed using PLINK. Expression was assessed using the Illumina HT12 array and analysed in R using a combination of Limma and Illuminaio. We identified three DMRs at HTR2A, SLC17A9 and HDAC4 that were consistent across both cohorts. The DMR at HTR2A is located within the bounds of a haplotype block; however, the DMR remained significant after accounting for SNPs in the region. No expression changes were detected in any DMRs. HTR2A is differentially methylated in progressive MS independent of genotype. This differential methylation is not evident in RRMS, making it a potential biomarker of progressive disease.]]> Mon 29 Jan 2024 17:52:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48683 1.97–7.77 µg/L) compared to quartile I (0.23–0.57 µg/L, reference). This study revealed that low blood cadmium levels <1.47 µg/L are probably associated with improved overall survival in treated patients with stage IA disease.]]> Mon 27 Mar 2023 14:53:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53956 Mon 22 Jan 2024 17:02:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42338 N = 29,125 cases and 34,836 controls), a robust polygenic signal was observed from gene sets based on TCF4, FMR1, upregulation from MIR137 and downregulation from CHD8. Additional analyses revealed a constant floor effect in the amount of variance explained, consistent with the omnigenic model. Thus, we report that putative core gene sets showed a significant effect above and beyond the floor effect that might be linked with the underlying omnigenic background. In addition, we demonstrate a method to quantify the contribution of specific gene sets within the omnigenic context.]]> Mon 22 Aug 2022 14:00:20 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53246 Mon 20 Nov 2023 10:14:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50311 Mon 17 Jul 2023 15:51:54 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50977 Mon 14 Aug 2023 15:24:38 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50972 Mon 14 Aug 2023 15:19:39 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43035 Mon 12 Sep 2022 11:49:25 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46970 Mon 12 Dec 2022 16:19:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51568 Mon 11 Sep 2023 14:22:09 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55070 Mon 08 Apr 2024 13:27:57 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42814 Mon 05 Sep 2022 14:06:54 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55449 13.6 μg/L) were associated with an increased risk of ovarian cancer (univariable: HR = 3.33; 95% CI: 1.23-9.00; p = 0.02; multivariable: HR = 2.10; 95% CI: 0.73-6.01; p = 0.17). No significant correlation was found with breast cancer risk. High blood lead levels are associated with increased risk of ovarian cancer in BRCA1 carriers, suggesting priority for preventive salpingo-oophorectomy. Potential risk reduction strategies include detoxification. Validation in diverse populations and exploration of detoxification methods for lowering lead levels are required.]]> Mon 03 Jun 2024 08:39:06 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55448 0.71 µg/L) had a significantly increased risk of cancer compared to those with low levels (<0.19 µg/L) (HR 3.42, p < 0.001), particularly among non-smokers (HR 3.74, p = 0.003), individuals aged < 60 years (HR 2.79, p = 0.017), and ≥60 (HR 4.63, p = 0.004). The influence of smoking on cancer risk based on Cd levels was not significant in this study. Blood Cd levels may influence cancer risk in men, emphasizing the importance of minimizing Cd exposure to reduce risk. Confirmation of these results in other populations is essential for effective preventive measures against Cd-related cancers.]]> Mon 03 Jun 2024 08:36:29 AEST ]]> 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 ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49672 Fri 26 May 2023 15:35:47 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42186 n = 3,473) by performing identity-by-descent (IBD) mapping followed by exome sequencing of individuals identified as sharing risk haplotypes to search for rare risk variants in coding regions. We identified 45 rare haplotypes (>1 cM) that were significantly more common in cases than controls. By exome sequencing 105 haplotype carriers, we investigated these haplotypes for functional coding variants that could be tested for association in independent GWAS samples. We identified one rare missense variant in PCNT but did not find statistical support for an association with schizophrenia in a replication analysis. However, IBD mapping can prioritize both individual samples and genomic regions for follow-up analysis but genome rather than exome sequencing may be more effective at detecting risk variants on rare haplotypes.]]> Fri 26 Aug 2022 10:49:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46592 n = 33). SNP-microarray analysis identified additional aberrations in 97% of patients (32/33) compared to conventional techniques. This changed the genomic risk category of 24% (8/33) of patients. Additionally, 27% (9/33) of patients exhibited a ‘hyperdiploid’ genome, which is generally associated with a good genomic risk and favourable outcomes. An enrichment of IKZF1 deletions was observed with one third of the cohort affected. Our findings suggest the current classification system could be improved and highlights the need to use more sensitive techniques such as SNP-microarray for cytogenomic risk stratification in B-ALL.]]> Fri 25 Nov 2022 15:04:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48644 Fri 24 Mar 2023 13:44:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48101 Fri 24 Feb 2023 15:38:03 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54935 Fri 22 Mar 2024 14:31:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46399 313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS₃₁₃ odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS₃₁₃ and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS₃₁₃ and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.]]> Fri 18 Nov 2022 14:15:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53114 Fri 17 Nov 2023 11:41:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51723 Fri 15 Sep 2023 17:53:26 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54828 Fri 15 Mar 2024 11:54:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47296 Fri 13 Jan 2023 10:45:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46091 Fri 11 Nov 2022 09:31:14 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42998 A and c.4534 C>T. Disease allele frequency was evaluated by genotyping of 1230 consecutive melanoma cases, 5000 breast cancer patients, 3500 prostate cancers and 9900 controls. Both variants were found to be absent among unselected cancer patients and healthy controls. The MutationTaster, Polyphen2 and SIFT algorithms indicate that c.9334G>A is a damaging variant. Due to lack of tumour tissue LOH analysis could not be performed for this variant. The variant segregated with the disease. The c.4534 C>T variant did not segregate with disease, there was no LOH of the variant. The c.9334G>A variant, classified as a rare variant of unknown significance, on current evidence may predisposes to cancers of the breast, prostate and melanoma. Functional studies to describe how the DNA change affects the protein function and a large multi-center study to evaluate its penetrance are required. © 2018 DeÎbniak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.]]> Fri 09 Sep 2022 14:03:47 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51559 Fri 08 Sep 2023 16:29:26 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51497 A (p.P.A148T) and survival of patients with bladder or kidney cancer remains controversial. Materials and Methods: We compared the allele frequencies of NOD2 c.3020insC and CDKN2A p.A148T allele in 706 patients with bladder cancer, 410 cases with kidney cancer against two control groups. The Cox proportional hazards model was used to determine whether there were any survival differences between carriers of the NOD2 c.3020insC or the CDKN2A p.A148T variant. Results: Among the three patient subgroups: patients under 60 years of age, non-smokers and a third with histological features of low grade noninvasive papillary bladder cancer, we observed that the c.3020insC allele had a nominal statistically significant effect on survival. We also observed that the NOD2 c.3020insC variant was more frequent in patients with bladder cancer aged between 51 and 60 years. There was some nominal evidence that the CDKN2A p.A148T polymorphism reduced survival in the subgroup of bladder cancer patients under 60 years of age. We observed that in kidney cancer patients, the incidence of the NOD2 variant appeared to be lower in the group aged between 60 and 70 years, however, this was not statistically significant. In addition, in patients with histological features of grade III chromophobic kidney cancer, the c.3020insC allele also appeared to be overrepresented but this too was not statistically significant. Conclusion: We have shown that the NOD2 c.3020insC allele and the CDKN2A p.A148T polymorphism does not play a role in the survival of patients with bladder cancer.]]> Fri 08 Sep 2023 11:56:10 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40367 Fri 08 Jul 2022 16:09:39 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37045 Fri 07 Aug 2020 14:34:14 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52991 Fri 03 Nov 2023 16:05:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47870 Fri 03 Feb 2023 14:42:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49791 Fri 02 Jun 2023 17:14:07 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51355 Fri 01 Sep 2023 13:43:26 AEST ]]>