2021 |
Kho P-F, Amant F, Annibali D, Ashton K, Attia J, Auer PL, et al., 'Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer', INTERNATIONAL JOURNAL OF CANCER, 148 307-319 (2021) [C1]
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Nova |
2021 |
Kho PF, Mortlock S, Rogers PAW, Nyholt DR, Montgomery GW, Spurdle AB, et al., 'Genetic analyses of gynecological disease identify genetic relationships between uterine fibroids and endometrial cancer, and a novel endometrial cancer genetic risk region at the WNT4 1p36.12 locus', HUMAN GENETICS, 140 1353-1365 (2021) [C1]
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2018 |
O'Mara TA, Glubb DM, Amant F, Annibali D, Ashton K, Attia J, et al., 'Identification of nine new susceptibility loci for endometrial cancer', NATURE COMMUNICATIONS, 9 (2018) [C1]
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Nova |
2018 |
Painter JN, O'Mara TA, Morris AP, Cheng THT, Gorman M, Martin L, et al., 'Genetic overlap between endometriosis and endometrial cancer: Evidence from cross-disease genetic correlation and GWAS meta-analyses', Cancer Medicine, 5 1978-1987 (2018) [C1]
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2016 |
Painter JN, O'Mara TA, Marquart L, Webb PM, Attia J, Medland SE, et al., 'Genetic risk score mendelian randomization shows that obesity measured as body mass index, but not waist:hip ratio, is causal for endometrial cancer', Cancer Epidemiology Biomarkers and Prevention, 25 1503-1510 (2016) [C1]
Background: The strongest known risk factor for endometrial cancer is obesity. To determine whether SNPs associated with increased body mass index (BMI) or waist-hip ratio (WHR) a... [more]
Background: The strongest known risk factor for endometrial cancer is obesity. To determine whether SNPs associated with increased body mass index (BMI) or waist-hip ratio (WHR) are associated with endometrial cancer risk, independent of measured BMI, we investigated relationships between 77 BMI and 47 WHR SNPs and endometrial cancer in 6,609 cases and 37,926 country-matched controls. Methods: Logistic regression analysis and fixed effects metaanalysis were used to test for associations between endometrial cancer risk and (i) individual BMI orWHRSNPs, (ii) a combined weighted genetic risk score (wGRS) for BMI or WHR. Causality of BMI for endometrial cancer was assessed using Mendelian randomization, with BMIwGRS as instrumental variable. Results: The BMIwGRS was significantly associated with endometrial cancer risk (P -= 3.4 × 10-17). Scaling the effect of the BMIwGRS on endometrial cancer risk by its effect on BMI, the endometrial cancer OR per 5 kg/m2 of genetically predicted BMI was 2.06 [95% confidence interval (CI), 1.89-2.21], larger than the observed effect of BMI on endometrial cancer risk (OR-=1.55; 95% CI, 1.44-1.68, per 5 kg/m2). The association attenuated but remained significant after adjusting for BMI (OR -= 1.22; 95% CI, 1.10-1.39; P -= 5.3 × 10-4). There was evidence of directional pleiotropy (P -= 1.5 × 10-4). BMI SNP rs2075650 was associated with endometrial cancer at study-wide significance (P < 4.0 × 10-4), independent of BMI. Endometrial cancer was not significantly associated with individual WHR SNPs or the WHRwGRS. Conclusions: BMI, but not WHR, is causally associated with endometrial cancer risk, with evidence that some BMI-associated SNPs alter endometrial cancer risk via mechanisms other than measurable BMI. Impact: The causal association between BMI SNPs and endometrial cancer has possible implications for endometrial cancer risk modeling.
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2016 |
Cheng THT, Thompson DJ, O'Mara TA, Painter JN, Glubb DM, Flach S, et al., 'Five endometrial cancer risk loci identified through genome-wide association analysis', Nature Genetics, 48 667-674 (2016) [C1]
We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 control... [more]
We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.31 (rs13328298, in LOC643623 and near HEY2 and NCOA7), 8q24.21 (rs4733613, telomeric to MYC), 15q15.1 (rs937213, in EIF2AK4, near BMF) and 14q32.33 (rs2498796, in AKT1, near SIVA1). We also found a second independent 8q24.21 signal (rs17232730). Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r 2 = 0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103[T] allele that is protective in endometrial cancer suppressed gene expression in vitro, suggesting that regulation of the expression of KLF5, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer.
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2016 |
Bowden NA, Smyth M, Jaaback K, Ashton KA, Scurry J, 'Genetic changes correlate with histopathology in a benign, borderline and malignant mucinous ovarian tumour', JOURNAL OF OBSTETRICS AND GYNAECOLOGY, 36 119-121 (2016)
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2016 |
Budden T, Davey RJ, Vilain RE, Ashton KA, Braye SG, Beveridge NJ, Bowden NA, 'Repair of UVB-induced DNA damage is reduced in melanoma due to low XPC and global genome repair', ONCOTARGET, 7 60940-60953 (2016) [C1]
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2016 |
Thompson DJ, O'Mara TA, Glubb DM, Painter JN, Cheng T, Folkerd E, et al., 'CYP19A1 fine-mapping and Mendelian randomization: Estradiol is causal for endometrial cancer', Endocrine-Related Cancer, 23 77-91 (2016) [C1]
Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancerandwith estradiol (E2) concentrations.We analyzed2937singlenucleotidepolymorphisms (S... [more]
Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancerandwith estradiol (E2) concentrations.We analyzed2937singlenucleotidepolymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome widesignificant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8×10-11). SNP rs727479 was also among those most strongly associated with circulating E2 concentrations in 2767 post-menopausal controls (P=7.4×10-8). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11-1.21) is compatible with that predicted by theobservedeffectonE2 concentrations (1.09, CI=1.03-1.21), consistentwith 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 associationswith rs727479 were stronger amongwomen with a higher BMI (PinteractionZ0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction.
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2016 |
Pringle KG, Delforce SJ, Wang Y, Ashton KA, Proietto A, Otton G, et al., 'Renin-angiotensin system gene polymorphisms and endometrial cancer', ENDOCRINE CONNECTIONS, 5 128-135 (2016) [C1]
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Nova |
2015 |
Cheng THT, Thompson D, Painter J, O'Mara T, Gorman M, Martin L, et al., 'Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1.', Sci Rep, 5 17369 (2015) [C1]
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Nova |
2015 |
Carvajal-Carmona LG, O Mara TA, Painter JN, Lose FA, Dennis J, Michailidou K, et al., 'Candidate locus analysis of the TERT CLPTM1L cancer risk region on chromosome 5p15 identifies multiple independent variants associated with endometrial cancer risk', Human Genetics, 134 231-245 (2015) [C1]
Several studies have reported associations between multiple cancer types and single-nucleotide polymorphisms (SNPs) on chromosome 5p15, which harbours TERT and CLPTM1L, but no suc... [more]
Several studies have reported associations between multiple cancer types and single-nucleotide polymorphisms (SNPs) on chromosome 5p15, which harbours TERT and CLPTM1L, but no such association has been reported with endometrial cancer. To evaluate the role of genetic variants at the TERT¿CLPTM1L region in endometrial cancer risk, we carried out comprehensive fine-mapping analyses of genotyped and imputed SNPs using a custom Illumina iSelect array which includes dense SNP coverage of this region. We examined 396 SNPs (113 genotyped, 283 imputed) in 4,401 endometrial cancer cases and 28,758 controls. Single-SNP and forward/backward logistic regression models suggested evidence for three variants independently associated with endometrial cancer risk (P¿=¿4.9¿×¿10-6 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.
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Nova |
2015 |
Ashton KA, Scurry J, Tabrizi SN, Garland SM, Otton G, Bowden NA, 'The problem of late ovarian metastases from primary cervical adenocarcinoma.', Gynecologic oncology reports, 13 23-25 (2015) [C3]
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2015 |
Aptekar S, Arora M, Lawrence CL, Lea RW, Ashton K, Dawson T, et al., 'Selective targeting to glioma with nucleic acid aptamers', PLoS ONE, 10 (2015)
Malignant glioma is characterised by a rapid growth rate and high capacity for invasive infiltration to surrounding brain tissue; hence, diagnosis and treatment is difficult and p... [more]
Malignant glioma is characterised by a rapid growth rate and high capacity for invasive infiltration to surrounding brain tissue; hence, diagnosis and treatment is difficult and patient survival is poor. Aptamers contribute a promising and unique technology for the in vitro imaging of live cells and tissues, with a potentially bright future in clinical diagnostics and therapeutics for malignant glioma. The binding selectivity, uptake capacity and binding target of two DNA aptamers, SA43 and SA44, were investigated in glioma cells and patient tissues. The binding assay showed that SA43 and SA44 bound with strong affinity (K<inf>d</inf>, 21.56 ± 4.60 nM and K<inf>d</inf>, 21.11 ± 3.30 nM respectively) to the target U87MG cells. Quantitative analysis by flow cytometry showed that the aptamers were able to actively internalise in U87MG and 1321N1 glioma cells compared to the non-cancerous and non-glioma cell types. Confocal microscopy confirmed staining in the cytoplasm, and co-localisation studies with endoplasmic reticulum, Golgi apparatus and lysosomal markers suggested internalisation and compartmentalisation within the endomembrane system. Both aptamers selectively bound to Ku 70 and Ku 80 DNA repair proteins as determined by aptoprecipitation (AP) followed by mass spectrometry analysis and confirmation by Western blot. In addition, aptohistochemical (AHC) staining on paraffin embedded, formalin fixed patient tissues revealed that the binding selectivity was significantly higher for SA43 aptamer in glioma tissues (grade I, II, III and IV) compared to the non-cancerous tissues, whereas SA44 did not show selectivity towards glioma tissues. The results indicate that SA43 aptamer can differentiate between glioma and non-cancerous cells and tissues and therefore, shows promise for histological diagnosis of glioma. Copyright:
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2015 |
Bowden NA, Beveridge NJ, Ashton KA, Baines KJ, Scott RJ, 'Understanding xeroderma pigmentosum complementation groups using gene expression profiling after UV-light exposure', International Journal of Molecular Sciences, 16 15985-15996 (2015) [C1]
Children with the recessive genetic disorder Xeroderma Pigmentosum (XP) have extreme sensitivity to UV-light, a 10,000-fold increase in skin cancers from age 2 and rarely live bey... [more]
Children with the recessive genetic disorder Xeroderma Pigmentosum (XP) have extreme sensitivity to UV-light, a 10,000-fold increase in skin cancers from age 2 and rarely live beyond 30 years. There are seven genetic subgroups of XP, which are all resultant of pathogenic mutations in genes in the nucleotide excision repair (NER) pathway and a XP variant resultant of a mutation in translesion synthesis, POLH. The clinical symptoms and severity of the disease is varied across the subgroups, which does not correlate with the functional position of the affected protein in the NER pathway. The aim of this study was to further understand the biology of XP subgroups, particularly those that manifest with neurological symptoms. Whole genome gene expression profiling of fibroblasts from each XP complementation group was assessed before and after UV-light exposure. The biological pathways with altered gene expression after UV-light exposure were distinct for each subtype and contained oncogenic related functions such as perturbation of cell cycle, apoptosis, proliferation and differentiation. Patients from the subgroups XP-B and XP-F were the only subgroups to have transcripts associated with neuronal activity altered after UV-light exposure. This study will assist in furthering our understanding of the different subtypes of XP which will lead to better diagnosis, treatment and management of the disease.
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Nova |
2015 |
Painter JN, O'Mara TA, Batra J, Cheng T, Lose FA, Dennis J, et al., 'Fine-mapping of the
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Nova |
2015 |
O'Mara TA, Glubb DM, Painter JN, Cheng T, Dennis J, Australian National Endometrial Cancer Study Group (ANECS), et al., 'Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer.', Endocr Relat Cancer, 22 851-861 (2015) [C1]
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Nova |
2014 |
Ashton KA, Scurry J, Ouveysi A, Ebbs J, Jaaback K, Bowden NA, 'Transformation of endometrioid carcinoma to carcinoma with trophoblastic differentiation: clinicopathological and whole genomic study.', Pathology, 46 351-353 (2014) [C3]
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2013 |
Talseth-Palmer B, Wijnen JT, Brenne IS, Jagmohan-Changur S, Barker DJ, Ashton KA, et al., 'Combined analysis of three Lynch syndrome cohorts confirms the modifying effects of 8q23.3 and 11q23.1 in MLH1 mutation carriers', International Journal of Cancer, 132 1487-1729 (2013) [C1]
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Nova |
2013 |
Bowden NA, Ashton KA, Vilain RE, Avery-Kiejda KA, Davey RJ, Murray HC, et al., 'Regulators of Global Genome Repair Do Not Respond to DNA Damaging Therapy but Correlate with Survival in Melanoma', PLOS ONE, 8 (2013) [C1]
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2012 |
Ashton KA, Scurry JP, Rutherford J, Otton GR, Scott R, Bowden NA, 'Nodular prurigo of the vulva', Pathology, 44 565-567 (2012) [C3]
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2012 |
Long J, Zheng W, Xiang Y-B, Lose F, Thompson D, Tomlinson I, et al., 'Genome-wide association study identifies a possible susceptibility locus for endometrial cancer', Cancer Epidemiology, Biomarkers & Prevention, 21 980-987 (2012) [C1]
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Nova |
2011 |
Kiejda KA, Bowden NA, Croft AJ, Scurr LL, Kairupan CF, Ashton KA, et al., 'P53 in human melanoma fails to regulate target genes associated with apoptosis and the cell cycle and may contribute to proliferation', BMC Cancer, 11 203-219 (2011) [C1]
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Nova |
2011 |
Talseth-Palmer B, Brenne IS, Ashton KA, Evans T-J, McPhillips M, Groombridge C, et al., 'Colorectal cancer susceptibility loci on chromosome 8q23.3 and 11q23.1 as modifiers for disease expression in lynch syndrome', Journal of Medical Genetics, 48 279-284 (2011) [C1]
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Nova |
2011 |
Australian Ntl Endometrial Cancer Study Group, Scott R, Ashton KA, Proietto AM, Otton GR, Ntl Study Of Endometrical Cancer Genetics Group, 'Genome-wide association study identifies a common variant associated with risk of endometrial cancer', Nature Genetics, 43 451-455 (2011) [C1]
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Nova |
2010 |
Proietto AM, Otton GR, Symonds IM, McEvoy MA, Attia JR, Gilbert M, et al., 'Polymorphisms in genes of the steroid hormone biosynthesis and metabolism pathways and endometrial cancer risk', Cancer Epidemiology, 34 328-337 (2010) [C1]
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Nova |
2010 |
Bowden NA, Ashton KA, Kiejda KA, Zhang XD, Hersey P, Scott R, 'Nucleotide excision repair gene expression after cisplatin treatment in melanoma', Cancer Research, 70 7918-7926 (2010) [C1]
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Nova |
2010 |
Ashton KA, Proietto AM, Otton GR, Symonds IM, McEvoy MA, Attia JR, Scott R, 'Toll-Like Receptor (TLR) and Nucleosome-binding Oligomerization Domain (NOD) gene polymorphisms and endometrial cancer risk', BMC Cancer, 10 1-7 (2010) [C1]
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Nova |
2009 |
Ashton KA, Proietto AM, Otton GR, Symonds IM, McEvoy MA, Attia JR, et al., 'Estrogen receptor polymorphisms and the risk of endometrial cancer', BJOG: An International Journal of Obstetrics and Gynaecology, 116 1053-1061 (2009) [C1]
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Nova |
2009 |
Ashton KA, Proietto AM, Otton GR, Symonds IM, Scott R, 'Genetic variants in MUTYH are not associated with endometrial cancer risk', Hereditary Cancer in Clinical Practice, 7 1-5 (2009) [C1]
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Nova |
2009 |
Ashton KA, Proietto AM, Otton GR, Symonds IM, McEvoy MA, Attia JR, et al., 'Polymorphisms in TP53 and MDM2 combined are associated with high grade endometrial cancer', Gynecologic Oncology, 113 109-114 (2009) [C1]
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Nova |
2008 |
Ashton KA, Proietto AM, Otton GR, Symonds IM, McEvoy MA, Attia JR, et al., 'The influence of the Cyclin D1 870 G\A polymorphism as an endometrial cancer risk factor', BMC Cancer, 8 1-6 (2008) [C1]
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Nova |
2008 |
Talseth-Palmer B, Ashton KA, Meldrum C, Suchy J, Kurzawski G, Lubinski J, Scott R, 'Aurora-A and Cyclin D1 polymorphisms and the age of onset of colorectal cancer in hereditary nonpolyposis colorectal cancer', International Journal of Cancer, 122 1273-1277 (2008) [C1]
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Nova |
2008 |
Dunning AM, Pooley KA, Chang-Claude J, Easton DF, Peto J, Houlston R, et al., 'Association of a common AKAP9 variant with breast cancer risk: A collaborative analysis', Journal of the National Cancer Institute, 100 437-442 (2008) [C1]
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Nova |
2006 |
Ashton KA, Meldrum CJ, McPhillips ML, Suchy J, Kurzawski G, Lubinski J, Scott R, 'The association of the COMT V158M polymorphism with endometrial/ovarian cancer in HNPCC families adhering to the Amsterdam criteria', Hereditary Cancer in Clinical Practice, 4 94-102 (2006) [C1]
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2005 |
Ashton KA, Meldrum CJ, McPhillips ML, Kairupan CF, Scott R, 'Frequency of the common MYH mutations (G382D and Y165C) in MMR mutation positive and negative HNPCC patients', Hereditary Cancer in Clinical Practice, 3 65-70 (2005) [C1]
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Nova |
2004 |
Scott R, Ashton KA, 'Familial breast and bowel cancer: Does it exist?', Hereditary Cancer in Clinical Practice, 2 25-59 (2004) [C1]
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