ORCID Profile
0000-0002-5452-4905
Current Organisations
KU Leuven
,
University of Amsterdam
,
Universitaire Ziekenhuizen Leuven
,
Antoni van Leeuwenhoek Nederlands Kanker Instituut
,
AMC
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Publications
Hospice nurses' perspectives of spirituality
Publisher: Wiley
Date: 28-06-2013
DOI: 10.1111/JOCN.12358
Abstract: To explore Singapore hospice nurses' perspectives of spirituality and spiritual care. A descriptive, cross-sectional design was used. Spiritual care is integral to providing quality end-of-life care. However, patients often report that this aspect of care is lacking. Previous studies suggest that nurses' neglect of this aspect of care could be attributed to poor understanding of what spirituality is and what such care entails. This study aimed to explore Singapore hospice nurses' perspectives about spirituality and spiritual care. A convenience s le of hospice nurses was recruited from the eight hospices in Singapore. The survey comprised two parts: the participant demographic details and the Spirituality Care-Giving Scale. This 35-item validated instrument measures participants' perspectives about spirituality and spiritual care. Sixty-six nurses participated (response rate of 65%). Overall, participants agreed with items in the Spiritual Care-Giving Scale related to Attributes of Spiritual Care Spiritual Perspectives Spiritual Care Attitudes and Spiritual Care Values. Results from general linear model analysis showed statistically significant main effects between race, spiritual affiliation and type of hospice setting, with the total Spiritual Care-Giving Scale score and four-factor scores. Spirituality was perceived to be universal, holistic and existential in nature. Spiritual care was perceived to be relational and centred on respecting patients' differing faiths and beliefs. Participants highly regarded the importance of spiritual care in the care of patients at end-of-life. Factors that significantly affected participants' perspectives of spirituality and spiritual care included race, spiritual affiliation and hospice type. Study can clarify values and importance of spirituality and care concepts in end-of-life care. Accordingly, spirituality and care issues can be incorporated in multi-disciplinary team discussions. Explicit guidelines regarding spiritual care and resources can be developed.
Breast cancer susceptibility polymorphisms and endometrial cancer risk: a Collaborative Endometrial Cancer Study
Publisher: Oxford University Press (OUP)
Date: 30-09-2011
Recovery from chemotherapy-induced white matter changes in young breast cancer survivors?
Publisher: Springer Science and Business Media LLC
Date: 19-01-2017
DOI: 10.1007/S11682-016-9665-8
Abstract: In a previous longitudinal diffusion tensor imaging (DTI) study, we observed cerebral white matter (WM) alterations (reduced fractional anisotropy (FA)) related to decreased cognitive performance 3-5 months after chemotherapy-treatment (t2) when compared to baseline (t1) (Deprez et al. in Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 30(3), 274-281. doi:10.1200/JCO.2011.36.8571, 2012). The current study investigates the evolution and the nature of these previously observed microstructural changes. Twenty-five young women with early-stage breast cancer who received chemotherapy treatment (C+), 14 who did not receive chemotherapy (C-) and 15 healthy controls (HC) previously studied, underwent reassessment 3-4 years after treatment (t3). We assessed (1) longitudinal changes of cognitive performance and FA and (2) cross-sectional group differences in myelin-water-imaging and multishell diffusion MRI metrics at t3. MRI metrics were assessed on a voxel-by-voxel basis and in regions-of-interest (ROI) in which previous WM injury was detected. Longitudinal results: Mixed-effects modeling revealed significant group-time interactions for verbal memory and processing speed (p < 0.05) reflecting regained performance in the C+ group at t3. Furthermore, in chemotherapy-treated patients, FA returned to baseline levels at t3 in all ROIs (p < 0.002), whereas no FA changes were seen in controls. Additionally, FA increase from t2 to t3 correlated with time since treatment in two of the four regions (r = 0.40, p < 0.05). Cross-sectional results: Advanced diffusion MRI and myelin-water imaging metrics in the ROIs did not differ between groups. Similarly, no whole-brain voxelwise differences were detected. Initial WM alterations and reduced cognitive performance following chemotherapy-treatment were found to recover in a group of young breast cancer survivors three to four years after treatment.
The PARAGON phase 2 trial of anastrozole in women with potentially hormone responsive recurrent/metastatic gynecologic neoplasms.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-05-2014
High-throughput interrogation of PIK3CA, PTEN, KRAS, FBXW7 and TP53 mutations in primary endometrial carcinoma
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.YGYNO.2012.11.037
Abstract: Endometrial cancer patients may benefit from systemic adjuvant chemotherapy, alone or in combination with targeted therapies. Prognostic and predictive markers are needed, however, to identify patients amenable for these therapies. Primary endometrial tumors were genotyped for >100 hot spot mutations in genes potentially acting as prognostic or predictive markers. Mutations were correlated with tumor characteristics in a discovery cohort, replicated in independent cohorts and finally, confirmed in the overall population (n=1063). PIK3CA, PTEN and KRAS mutations were most frequently detected, respectively in 172 (16.2%), 164 (15.4%) and 161 (15.1%) tumors. Binary logistic regression revealed that PIK3CA mutations were more common in high-grade tumors (OR=2.03 P=0.001 for grade 2 and OR=1.89 P=0.012 for grade 3 compared to grade 1), whereas a positive TP53 status correlated with type II tumors (OR=11.92 P<0.001) and PTEN mutations with type I tumors (OR=19.58 P=0.003). Conversely, FBXW7 mutations correlated with positive lymph nodes (OR=3.38 P=0.045). When assessing the effects of in idual hot spot mutations, the H1047R mutation in PIK3CA correlated with high tumor grade and reduced relapse-free survival (HR=2.18 P=0.028). Mutations in PIK3CA, TP53, PTEN and FBXW7 correlate with high tumor grade, endometrial cancer type and lymph node status, whereas PIK3CA H1047R mutations serve as prognostic markers for relapse-free survival in endometrial cancer patients.
Polymorphisms in Stromal Genes and Susceptibility to Serous Epithelial Ovarian Cancer: A Report from the Ovarian Cancer Association Consortium
Publisher: Public Library of Science (PLoS)
Date: 27-05-2011
Progesterone receptor gene variants and risk of endometrial cancer
Publisher: Oxford University Press (OUP)
Date: 10-12-2010
Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer
Publisher: American Association for Cancer Research (AACR)
Date: 31-10-2016
DOI: 10.1158/1055-9965.EPI-16-0147
Abstract: 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 meta-analysis were used to test for associations between endometrial cancer risk and (i) in idual BMI or WHR SNPs, (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 in idual 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. Cancer Epidemiol Biomarkers Prev 25(11) 1503–10. ©2016 AACR.
Gynecologic Cancer InterGroup (GCIG) Consensus Review for Endometrial Stromal Sarcoma
Publisher: BMJ
Date: 11-2014
DOI: 10.1097/IGC.0000000000000205
Abstract: Endometrial stromal sarcoma (ESS) accounts for approximately 20% of all uterine sarcomas and presents, at a mean age, around 50 years of age. Half of the patients are premenopausal. ESS often manifests as an endometrial polyp and 60% of cases present with FIGO stage I disease. The natural history is one of slow growing indolent disease. Typical microscopic findings include a uniform population of endometrial stromal-type cells invading the myometrium and myometrial vessels. Imaging studies cannot reliably diagnose ESS preoperatively, so surgical resection for a presumed fibroid is a common scenario. Hysterectomy is the cornerstone of treatment for localized ESS, but morcellation should be avoided. Systematic lymphadenectomy in ESS does not improve the outcome. Leaving the ovaries in situ does not worsen survival and this is of importance especially for young women. The data support the current practice to administer adjuvant hormonal treatment, although several questions remain, such as optimal doses, regimens (progestins or aromatase inhibitors) and duration of therapy. Repeat surgery for recurrent disease that is indolent and hormone sensitive appears to be an acceptable approach. Systemic treatment for recurrent disease is mainly hormonal.
Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer
Publisher: Bioscientifica
Date: 10-2015
DOI: 10.1530/ERC-15-0319
Abstract: Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1 . Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6607 EC cases and 37 925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P =1.86×10 −5 ), which was stronger for cancers of endometrioid subtype ( P =3.76×10 −6 ). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1 , and eQTL analysis found that rs79575945 was associated with expression of SYNE1 , a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1 , at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types.
Antisense oligonucleotide–mediated MDM4 exon 6 skipping impairs tumor growth
Publisher: American Society for Clinical Investigation
Date: 23-11-2015
DOI: 10.1172/JCI82534
Identification of nine new susceptibility loci for endometrial cancer
Publisher: Springer Science and Business Media LLC
Date: 09-08-2018
DOI: 10.1038/S41467-018-05427-7
Abstract: Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins ( SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.
Genome-Wide Association Study Identifies a Possible Susceptibility Locus for Endometrial Cancer
Publisher: American Association for Cancer Research (AACR)
Date: 06-2012
DOI: 10.1158/1055-9965.EPI-11-1160
Abstract: Background: Genome-wide association studies (GWAS) have identified more than 100 genetic loci for various cancers. However, only one is for endometrial cancer. Methods: We conducted a three-stage GWAS including 8,492 endometrial cancer cases and 16,596 controls. After analyzing 585,963 single-nucleotide polymorphisms (SNP) in 832 cases and 2,682 controls (stage I) from the Shanghai Endometrial Cancer Genetics Study, we selected the top 106 SNPs for in silico replication among 1,265 cases and 5,190 controls from the Australian/British Endometrial Cancer GWAS (stage II). Nine SNPs showed results consistent in direction with stage I with P & 0.1. These nine SNPs were investigated among 459 cases and 558 controls (stage IIIa) and six SNPs showed a direction of association consistent with stages I and II. These six SNPs, plus two additional SNPs selected on the basis of linkage disequilibrium and P values in stage II, were investigated among 5,936 cases and 8,166 controls from an additional 11 studies (stage IIIb). Results: SNP rs1202524, near the CAPN9 gene on chromosome 1q42.2, showed a consistent association with endometrial cancer risk across all three stages, with ORs of 1.09 [95% confidence interval (CI), 1.03–1.16] for the A/G genotype and 1.17 (95% CI, 1.05–1.30) for the G/G genotype (P = 1.6 × 10−4 in combined analyses of all s les). The association was stronger when limited to the endometrioid subtype, with ORs (95% CI) of 1.11 (1.04–1.18) and 1.21 (1.08–1.35), respectively (P = 2.4 × 10−5). Conclusions: Chromosome 1q42.2 may host an endometrial cancer susceptibility locus. Impact: This study identified a potential genetic locus for endometrial cancer risk. Cancer Epidemiol Biomarkers Prev 21(6) 980–7. ©2012 AACR.
No Association between FTO or HHEX and Endometrial Cancer Risk
Publisher: American Association for Cancer Research (AACR)
Date: 08-2010
DOI: 10.1158/1055-9965.EPI-10-0515
Abstract: Introduction: Obesity and diabetes are known risk factors for endometrial cancer thus, the genetic risk factors of these phenotypes might also be associated with endometrial cancer risk. To evaluate this hypothesis, we genotyped tag-single nucleotide polymorphisms (SNP) and candidate SNPs in FTO and HHEX in a primary set of 417 endometrial cancer cases and 406 population-based controls, and validated significant findings in a replication set of approximately 2,347 cases and 3,140 controls from three additional studies. Methods: We genotyped 189 tagSNPs in FTO (including rs8050136) and five tagSNPs in HHEX (including rs1111875) in the primary set and one SNP each in FTO (rs12927155) and HHEX (rs1111875) in the validation set. Per allele odds ratios (OR) and 95% confidence intervals (CI) were calculated to estimate the association between the genotypes of each SNPs (as an ordinal variable) and endometrial cancer risk using unconditional logistic regression models, controlling for age and site. Results: In the primary study, the most significant finding in FTO was rs12927155 (OR, 1.56 95% CI, 1.21-2.01 P = 5.8 × 10−4), and in HHEX, it was rs1111875 (OR, 0.80 95% CI, 0.66-0.97 P = 0.026). In the validation studies, the pooled per allele OR, adjusted for age and study for FTO, was rs12927155 (OR, 0.94 95% CI, 0.83-1.06 P = 0.29), whereas for HHEX, it was rs1111875 (OR, 1.00 95% CI, 0.92-1.10 P = 0.96). Conclusion: Our data indicate that common genetic variants in two genes previously related to obesity (FTO) and diabetes (HHEX) by genome-wide association scans were not associated with endometrial cancer risk. Impact: Polymorphisms in FTO and HHEX are unlikely to have large effects on endometrial cancer risk but may have weaker effects. Cancer Epidemiol Biomarkers Prev 19(8) 2106–9. ©2010 AACR.
Longitudinal Assessment of Chemotherapy-Induced Alterations in Brain Activation During Multitasking and Its Relation With Cognitive Complaints
Publisher: American Society of Clinical Oncology (ASCO)
Date: 07-2014
Abstract: To examine whether cognitive complaints after treatment for breast cancer are associated with detectable changes in brain activity during multitasking. Eighteen patients who were scheduled to receive chemotherapy performed a functional magnetic resonance imaging multitasking task in the scanner before the start of treatment (t1) and 4 to 6 months after finishing treatment (t2). Sixteen patients who were not scheduled to receive chemotherapy and 17 matched healthy controls performed the same task at matched intervals. Task difficulty level was adjusted in idually to match performance across participants. Statistical Parametric Mapping 8 (SPM8) software was used for within-group, between-group, and group-by-time interaction image analyses. Voxel-based paired t tests revealed significantly decreased activation (P .05) from t1 to t2 at matched performance in the multitasking network of chemotherapy-treated patients, whereas no changes were noted in either of the control groups. At baseline, there were no differences between the groups. Furthermore, in contrast to controls, the chemotherapy-treated patients reported a significant increase in cognitive complaints (P .05) at t2. Significant (P .05) correlations were found between these increases and decreases in multitasking-related brain activation. Moreover, a significant group-by-time interaction (P .05) was found whereby chemotherapy-treated patients showed decreased activation and healthy controls did not. These results suggest that changes in brain activity may underlie chemotherapy-induced cognitive complaints. The observed changes might be related to chemotherapy-induced damage to the brain or reduced connectivity between brain regions rather than to changes in effort or changes in functional strategy. To the best of our knowledge, this is the first longitudinal study providing evidence for a relationship between longitudinal changes in cognitive complaints and changes in brain activation after chemotherapy.
Common variants at 19p13 are associated with susceptibility to ovarian cancer
Publisher: Springer Science and Business Media LLC
Date: 19-09-2010
DOI: 10.1038/NG.666
A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24
Publisher: Springer Science and Business Media LLC
Date: 19-09-2010
DOI: 10.1038/NG.668
Variability in CRP, regulatory T cells and effector T cells over time in gynaecological cancer patients: a study of potential oscillatory behaviour and correlations
Publisher: Springer Science and Business Media LLC
Date: 23-06-2014
Abstract: The inflammatory marker, C reactive protein has been proposed to also be a biomarker for adaptive immune responses in cancer patients with a possible application in time based chemotherapy. Fluxes in serum CRP levels were suggested to be indicative of a cyclical process in which, immune activation is followed by auto-regulating immune suppression. The applicability of CRP as a biomarker for regulatory or effector T cells was therefore investigated in a cohort of patients with gynaecological malignancies. Peripheral blood s les were obtained from a cohort of patients at 7 time points over a period of 12 days. Serum and mononuclear cells were isolated and CRP levels in serum were detected using ELISA while regulatory and effector T cell frequencies were assessed using flow cytometry. To test periodicity, periodogram analysis of data was employed while Pearson correlation and the Wilcoxon signed rank test were used to determine correlations. The statistical analysis used showed no evidence of periodic oscillation in either serum CRP concentrations or T eff and T reg frequencies. Furthermore, there was no apparent correlation between serum CRP concentrations and the corresponding frequencies of T regs or T effs . Relative to healthy in iduals, the disease state in the patients neither significantly affected the mean frequency of T regs nor the mean coefficient of variation within the T reg population over time. However, both T eff mean frequency and mean coefficient of variation were significantly reduced in patients. Using our methods we were unable to detect CRP oscillations that could be used as a consistent serial biomarker for time based chemotherapy.
Somatic POLE exonuclease domain mutations are early events in sporadic endometrial and colorectal carcinogenesis, determining driver mutational landscape, clonal neoantigen burden and immune re
Publisher: Wiley
Date: 30-04-2018
DOI: 10.1002/PATH.5081
Polymorphisms in Inflammation Pathway Genes and Endometrial Cancer Risk
Publisher: American Association for Cancer Research (AACR)
Date: 02-2013
DOI: 10.1158/1055-9965.EPI-12-0903
Abstract: Background: Experimental and epidemiologic evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. Methods: To investigate this hypothesis, a two-stage study was carried out to evaluate single-nucleotide polymorphisms (SNP) in inflammatory pathway genes in association with endometrial cancer risk. In stage I, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage I SNPs significantly associated with endometrial cancer (P & 0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. One SNP from each of the 24 loci was then selected for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in stage II, which consisted of 10 additional studies including 6,604 endometrial cancer cases and 8,511 controls. Results: Five of the 21 SNPs had significant allelic odds ratios (ORs) and 95% confidence intervals (CI) as follows: FABP1, 0.92 (0.85–0.99) CXCL3, 1.16 (1.05–1.29) IL6, 1.08 (1.00–1.17) MSR1, 0.90 (0.82–0.98) and MMP9, 0.91 (0.87–0.97). Two of these polymorphisms were independently significant in the replication s le (rs352038 in CXCL3 and rs3918249 in MMP9). The association for the MMP9 polymorphism remained significant after Bonferroni correction and showed a significant association with endometrial cancer in both Asian- and European-ancestry s les. Conclusions: These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer. Impact statement: This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis. Cancer Epidemiol Biomarkers Prev 22(2) 216–23. ©2012 AACR.
Pan-cancer detection and typing by mining patterns in large genome-wide cell-free DNA sequencing datasets
Publisher: Cold Spring Harbor Laboratory
Date: 20-02-2022
DOI: 10.1101/2022.02.16.22268780
Abstract: Cell-free DNA (cfDNA) analysis holds great promise for non-invasive cancer screening, diagnosis and monitoring. We hypothesized that mining the patterns of big datasets of shallow whole genome sequencing cfDNA from cancer patients could improve cancer detection. By applying unsupervised clustering and supervised machine learning on large shallow whole-genome sequencing cfDNA datasets from healthy in iduals (n=367), patients with different hematological (n=238) and solid malignancies (n=320), we identify cfDNA signatures that enable cancer detection and typing. Unsupervised clustering revealed cancer-type-specific sub-grouping. Classification using supervised machine learning model yielded an overall accuracy of 81.62% in discriminating malignant from control s les. The accuracy of disease type prediction was 85% and 70% for the hematological and solid cancers, respectively. We demonstrate the clinical utility of our approach by classifying benign from invasive and borderline adnexal masses with an AUC of 0.8656 and 0.7388, respectively. This approach provides a generic and cost-effective strategy for non-invasive pan-cancer detection.
Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers
Publisher: American Association for Cancer Research (AACR)
Date: 2021
DOI: 10.1158/1055-9965.EPI-20-0739
Abstract: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers. Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data. Genetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10−5). We found seven loci associated with risk for both cancers (PBonferroni & 2.4 × 10−9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P & 5 × 10−7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation. Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis. Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger s le sets are required to confirm our findings.
An international real-world analysis of relapsed/refractory lymphoma occurring during pregnancy
Publisher: American Society of Hematology
Date: 15-09-2023
PARAGON (ANZGOG-0903): a phase 2 study of anastrozole in asymptomatic patients with estrogen and progesterone receptor-positive recurrent ovarian cancer and CA125 progression
Publisher: Asian Society of Gynecologic Oncology; Korean Society of Gynecologic Oncology and Colposcopy
Date: 2019
The functional neuroanatomy of multitasking: Combining dual tasking with a short term memory task
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2013.07.024
Abstract: Insight into the neural architecture of multitasking is crucial when investigating the pathophysiology of multitasking deficits in clinical populations. Presently, little is known about how the brain combines dual-tasking with a concurrent short-term memory task, despite the relevance of this mental operation in daily life and the frequency of complaints related to this process, in disease. In this study we aimed to examine how the brain responds when a memory task is added to dual-tasking. Thirty-three right-handed healthy volunteers (20 females, mean age 39.9 ± 5.8) were examined with functional brain imaging (fMRI). The paradigm consisted of two cross-modal single tasks (a visual and auditory temporal same-different task with short delay), a dual-task combining both single tasks simultaneously and a multi-task condition, combining the dual-task with an additional short-term memory task (temporal same-different visual task with long delay). Dual-tasking compared to both in idual visual and auditory single tasks activated a predominantly right-sided fronto-parietal network and the cerebellum. When adding the additional short-term memory task, a larger and more bilateral frontoparietal network was recruited. We found enhanced activity during multitasking in components of the network that were already involved in dual-tasking, suggesting increased working memory demands, as well as recruitment of multitask-specific components including areas that are likely to be involved in online holding of visual stimuli in short-term memory such as occipito-temporal cortex. These results confirm concurrent neural processing of a visual short-term memory task during dual-tasking and provide evidence for an effective fMRI multitasking paradigm.
Five endometrial cancer risk loci identified through genome-wide association analysis
Publisher: Springer Science and Business Media LLC
Date: 02-05-2016
DOI: 10.1038/NG.3562
CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer
Publisher: Bioscientifica
Date: 16-11-2015
DOI: 10.1530/ERC-15-0386
Abstract: Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol (E 2 ) concentrations. We analyzed 2937 single nucleotide polymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome wide-significant 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 E 2 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 the observed effect on E 2 concentrations (1.09, CI=1.03–1.21), consistent with the hypothesis that endometrial cancer risk is driven by E 2 . 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.
Genetic overlap between endometriosis and endometrial cancer: evidence from cross‐disease genetic correlation and GWAS meta‐analyses
Publisher: Wiley
Date: 02-04-2018
DOI: 10.1002/CAM4.1445
Abstract: Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation ( r g = 0.23, P = 9.3 × 10 −3 ), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy ( P = 6.0 × 10 −3 ) and concordance in effect direction ( P = 2.0 × 10 −3 ) between the two diseases. Cross‐disease GWAS meta‐analysis highlighted 13 distinct loci associated at P ≤ 10 −5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level ( P = 4.9 × 10 −8 , OR = 1.11, 95% CI = 1.07–1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross‐disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.
Genome-wide association study identifies a common variant associated with risk of endometrial cancer
Publisher: Springer Science and Business Media LLC
Date: 17-04-2011
DOI: 10.1038/NG.812
Related Organisations
Antoni Van Leeuwenhoek Nederlands Kanker Instituut
Location: Netherlands
Related Funding Activities
No related grants have been discovered for Frédéric Amant.