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4. Chemoradiation for muscle-invasive bladder cancer using 5-fluorouracil versus capecitabine

Author

Haar-Holleman, Amy de, Hoogstraten, L.M.C. van, Hulshof, Maarten C.C.M., Tascilar, M., Bruck, Katharin, Meijer, Richard P., Witjes, J.A., Kiemeney, L.A., Aben, K.K.H., CCA - Cancer Treatment and Quality of Life, and Radiotherapy

Subjects
Drug toxicity, All institutes and research themes of the Radboud University Medical Center, Oncology, Survival, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 5-Fluorouracil, Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], Bladder cancer, Radiology, Nuclear Medicine and imaging, Hematology, Chemoradiotherapy, Capecitabine
Abstract

Background and purpose: Oral capecitabine and intravenous 5-fluorouracil (5-FU) are both used as a radiosensitizer in chemoradiotherapy (CRT). A capecitabine-based regimen is more convenient for both patients and healthcare professionals. Since large comparative studies are lacking, we compared toxicity, overall survival (OS) and disease-free survival (DFS) between both CRT-regimens in patients with muscle-invasive bladder cancer (MIBC). Materials and methods: All patients diagnosed with non-metastatic MIBC between November 2017-November 2019 were consecutively included in the BlaZIB study. Data on patient, tumor, treatment characteristics and toxicity were prospectively collected from the medical files. From this cohort, all patients with cT2-4aN0-2/xM0/x, treated with capecitabine or 5-FU-based CRT were included in the current study. Toxicity in both groups was compared using Fisher-exact tests. Propensity score-based inverse probability treatment weighting (IPTW) was applied to correct for baseline differences between groups. IPTW-adjusted Kaplan-Meier OS and DFS curves were compared using log-rank tests. Results: Of the 222 included patients, 111 (50%) were treated with 5-FU and 111 (50%) with capecitabine. Curative CRT was completed according to treatment plan in 77% of patients in the capecitabine-based group and 62% of the 5-FU group (p = 0.06). Adverse events (14 vs 21%, p = 0.29), 2-year OS (73% vs 61%, p = 0.07) and 2-year DFS (56% vs 50%, p = 0.50) did not differ significantly between groups. Conclusions: Chemoradiotherapy with capecitabine and MMC is associated with a similar toxicity profile compared to 5-FU plus MMC and no difference in survival was found. Capecitabine-based CRT, as a more patient-friendly schedule, may be considered as an alternative to a 5-FU-based regimen.

Published
2023

5. Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis.

Author

Fu, Z., Brooks, M.M., Irvin, S., Jordan, S., Aben, K.K.H., Anton-Culver, H., Bandera, E.V., Beckmann, M.W., Berchuck, A., Brooks-Wilson, A., Chang-Claude, J., Cook, L.S., Cramer, D.W, Cushing-Haugen, K.L., Doherty, J.A., Ekici, A.B., Fasching, P.A., Fortner, R.T., Gayther, S.A., Gentry-Maharaj, A., Giles, G.G., Goode, E.L., Goodman, M.T., Harris, H.R., Hein, A., Kaaks, R., Kiemeney, L.A., Köbel, M., Kotsopoulos, J., Le, N.D., Lee, A.W.C., Matsuo, K., McGuire, V., McLaughlin, J.R., Menon, U., Milne, R.L., Moysich, K.B., Pearce, C.L., Pike, M.C., Qin, B., Ramus, S.J., Riggan, M.J., Rothstein, J.H., Schildkraut, J.M., Sieh, W., Sutphen, R., Terry, K.L., Thompson, P.J., Titus, L., Altena, A.M. van, White, E., Whittemore, A.S., Wu, A.H., Zheng, W., Ziogas, Argyrios, Taylor, S.E., Tang, L., Songer, T., Wentzensen, N., Webb, P.M., Risch, H.A., Modugno, F., Fu, Z., Brooks, M.M., Irvin, S., Jordan, S., Aben, K.K.H., Anton-Culver, H., Bandera, E.V., Beckmann, M.W., Berchuck, A., Brooks-Wilson, A., Chang-Claude, J., Cook, L.S., Cramer, D.W, Cushing-Haugen, K.L., Doherty, J.A., Ekici, A.B., Fasching, P.A., Fortner, R.T., Gayther, S.A., Gentry-Maharaj, A., Giles, G.G., Goode, E.L., Goodman, M.T., Harris, H.R., Hein, A., Kaaks, R., Kiemeney, L.A., Köbel, M., Kotsopoulos, J., Le, N.D., Lee, A.W.C., Matsuo, K., McGuire, V., McLaughlin, J.R., Menon, U., Milne, R.L., Moysich, K.B., Pearce, C.L., Pike, M.C., Qin, B., Ramus, S.J., Riggan, M.J., Rothstein, J.H., Schildkraut, J.M., Sieh, W., Sutphen, R., Terry, K.L., Thompson, P.J., Titus, L., Altena, A.M. van, White, E., Whittemore, A.S., Wu, A.H., Zheng, W., Ziogas, Argyrios, Taylor, S.E., Tang, L., Songer, T., Wentzensen, N., Webb, P.M., Risch, H.A., and Modugno, F.

Abstract

Item does not contain fulltext, BACKGROUND: The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC. METHODS: LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source. RESULTS: LOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes. CONCLUSIONS: LOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC.

Published
2023

6. Genome-wide Association Study of Bladder Cancer Reveals New Biological and Translational Insights.

Author

Koutros, S., Kiemeney, L.A., Pal Choudhury, P., Milne, R.L., Lopez de Maturana, E., Ye, Y., Joseph, V., Florez-Vargas, O., Dyrskjøt, L., Figueroa, J., Dutta, D., Giles, G.G., Hildebrandt, M.A.T., Offit, K., Kogevinas, M., Weiderpass, E., McCullough, M.L., Freedman, N.D., Albanes, D., Kooperberg, C., Cortessis, V.K., Karagas, M.R., Johnson, A., Schwenn, M.R., Baris, D., Furberg, H., Bajorin, D.F., Cussenot, O., Cancel-Tassin, G., Benhamou, S., Kraft, P., Porru, S., Carta, A., Bishop, T., Southey, M.C., Matullo, G., Fletcher, T., Kumar, R., Taylor, J.A., Lamy, P., Prip, F., Kalisz, M., Weinstein, S.J., Hengstler, J.G., Selinski, S., Harland, M., Teo, M., Kiltie, A.E., Tardón, A., Serra, C., Carrato, A., García-Closas, R., Lloreta, J., Schned, A., Lenz, P., Riboli, E., Brennan, P., Tjønneland, A., Otto, T., Ovsiannikov, D., Volkert, F., Vermeulen, S.H., Aben, K.K.H., Galesloot, T.E., Turman, C., Vivo, I. De, Giovannucci, E., Hunter, D.J., Hohensee, C., Hunt, R., Patel, A.V., Huang, W.Y., Thorleifsson, G., Gago-Dominguez, M., Amiano, P., Golka, K., Stern, M.C., Yan, W., Liu, J., Li, S.A., Katta, S., Hutchinson, A., Hicks, B., Wheeler, W.A., Purdue, M.P., McGlynn, K.A., Kitahara, C.M., Haiman, C.A., Greene, M.H., Rafnar, T., Chatterjee, N., Chanock, S.J., Wu, X., Real, F.X., Silverman, D.T., Garcia-Closas, M., Stefansson, K., Prokunina-Olsson, L., Malats, N., Rothman, N., Koutros, S., Kiemeney, L.A., Pal Choudhury, P., Milne, R.L., Lopez de Maturana, E., Ye, Y., Joseph, V., Florez-Vargas, O., Dyrskjøt, L., Figueroa, J., Dutta, D., Giles, G.G., Hildebrandt, M.A.T., Offit, K., Kogevinas, M., Weiderpass, E., McCullough, M.L., Freedman, N.D., Albanes, D., Kooperberg, C., Cortessis, V.K., Karagas, M.R., Johnson, A., Schwenn, M.R., Baris, D., Furberg, H., Bajorin, D.F., Cussenot, O., Cancel-Tassin, G., Benhamou, S., Kraft, P., Porru, S., Carta, A., Bishop, T., Southey, M.C., Matullo, G., Fletcher, T., Kumar, R., Taylor, J.A., Lamy, P., Prip, F., Kalisz, M., Weinstein, S.J., Hengstler, J.G., Selinski, S., Harland, M., Teo, M., Kiltie, A.E., Tardón, A., Serra, C., Carrato, A., García-Closas, R., Lloreta, J., Schned, A., Lenz, P., Riboli, E., Brennan, P., Tjønneland, A., Otto, T., Ovsiannikov, D., Volkert, F., Vermeulen, S.H., Aben, K.K.H., Galesloot, T.E., Turman, C., Vivo, I. De, Giovannucci, E., Hunter, D.J., Hohensee, C., Hunt, R., Patel, A.V., Huang, W.Y., Thorleifsson, G., Gago-Dominguez, M., Amiano, P., Golka, K., Stern, M.C., Yan, W., Liu, J., Li, S.A., Katta, S., Hutchinson, A., Hicks, B., Wheeler, W.A., Purdue, M.P., McGlynn, K.A., Kitahara, C.M., Haiman, C.A., Greene, M.H., Rafnar, T., Chatterjee, N., Chanock, S.J., Wu, X., Real, F.X., Silverman, D.T., Garcia-Closas, M., Stefansson, K., Prokunina-Olsson, L., Malats, N., and Rothman, N.

Abstract

01 juli 2023, Item does not contain fulltext, BACKGROUND: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology. OBJECTIVE: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data. DESIGN, SETTING, AND PARTICIPANTS: Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. A polygenic risk score (PRS) was generated on the basis of known and novel susceptibility variants and tested for interaction with smoking. RESULTS AND LIMITATIONS: Multiple novel bladder cancer susceptibility loci (6p.22.3, 7q36.3, 8q21.13, 9p21.3, 10q22.1, 19q13.33) as well as improved signals in three known regions (4p16.3, 5p15.33, 11p15.5) were identified, bringing the number of independent markers at genome-wide significance (p < 5 × 10(-8)) to 24. The 4p16.3 (FGFR3/TACC3) locus was associated with a stronger risk for women than for men (p-interaction = 0.002). Bladder cancer risk was increased by interactions between smoking status and genetic variants at 8p22 (NAT2; multiplicative p value for interaction [p(M-I)] = 0.004), 8q21.13 (PAG1; p(M-I) = 0.01), and 9p21.3 (LOC107987026/MTAP/CDKN2A; p(M-I) = 0.02). The PRS based on the 24 independent GWAS markers (odds ratio per standard deviation increase 1.49, 95% confidence interval 1.44-1.53), which also showed comparable results in two prospective cohorts (UK Biobank, PLCO trial), revealed an approximately fourfold difference in the lifetime risk of bladder cancer according to the PRS (e.g., 1st vs 10th decile) for both smokers and nonsmokers. CONCLUSIONS: We report novel loci ass

Published
2023

7. Clinical parameters affecting survival outcomes in patients with low-grade serous ovarian carcinoma: an international multicentre analysis

Author

May, T., Bernardini, M., Lheureux, S., Aben, K.K.H., Bandera, E.V., Beckmann, M.W., Benitez, J., Berchuck, A., Kiemeney, L.A., Altena, A.M. van, Jiang, Haiyan, Tone, A., May, T., Bernardini, M., Lheureux, S., Aben, K.K.H., Bandera, E.V., Beckmann, M.W., Benitez, J., Berchuck, A., Kiemeney, L.A., Altena, A.M. van, Jiang, Haiyan, and Tone, A.

Abstract

Item does not contain fulltext

Published
2023

9. Epidemiology of Bladder Cancer in 2023: A Systematic Review of Risk Factors.

Author

Jubber, I., Ong, S., Bukavina, L., Black, P.C., Compérat, E., Kamat, A.M., Kiemeney, L.A., Lawrentschuk, N., Lerner, S.P., Meeks, J.J., Moch, H., Necchi, A., Panebianco, V, Sridhar, S.S., Znaor, A., Catto, J.W.F., Cumberbatch, M.G., Jubber, I., Ong, S., Bukavina, L., Black, P.C., Compérat, E., Kamat, A.M., Kiemeney, L.A., Lawrentschuk, N., Lerner, S.P., Meeks, J.J., Moch, H., Necchi, A., Panebianco, V, Sridhar, S.S., Znaor, A., Catto, J.W.F., and Cumberbatch, M.G.

Abstract

01 augustus 2023, Contains fulltext : 294936.pdf (Publisher’s version ) (Open Access), CONTEXT: Bladder cancer (BC) is common worldwide and poses a significant public health challenge. External risk factors and the wider exposome (totality of exposure from external and internal factors) contribute significantly to the development of BC. Therefore, establishing a clear understanding of these risk factors is the key to prevention. OBJECTIVE: To perform an up-to-date systematic review of BC's epidemiology and external risk factors. EVIDENCE ACQUISITION: Two reviewers (I.J. and S.O.) performed a systematic review using PubMed and Embase in January 2022 and updated it in September 2022. The search was restricted to 4 yr since our previous review in 2018. EVIDENCE SYNTHESIS: Our search identified 5177 articles and a total of 349 full-text manuscripts. GLOBOCAN data from 2020 revealed an incidence of 573 000 new BC cases and 213 000 deaths worldwide in 2020. The 5-yr prevalence worldwide in 2020 was 1 721 000. Tobacco smoking and occupational exposures (aromatic amines and polycyclic aromatic hydrocarbons) are the most substantial risk factors. In addition, correlative evidence exists for several risk factors, including specific dietary factors, imbalanced microbiome, gene-environment risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy. CONCLUSIONS: We present a contemporary overview of the epidemiology of BC and the current evidence for BC risk factors. Smoking and specific occupational exposures are the most established risk factors. There is emerging evidence for specific dietary factors, imbalanced microbiome, gene-external risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy. Further high-quality evidence is required to confirm initial findings and further understand cancer prevention. PATIENT SUMMARY: Bladder cancer is common, and the most substantial risk factors are smoking and workplace exposure to suspected carcinogens. On-going research to identify avoidable risk factors could reduce t

Published
2023

10. The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis

Author

Xu, Y.F., Derakhshan, A., Hysaj, O., Wildisen, L., Ittermann, T., Pingitore, A., Abolhassani, N., Medici, M., Kiemeney, L.A., Riksen, N.P., Dullaart, R.P.F., Trompet, S., Dörr, M., Brown, S.J., Schmidt, Börge, Führer-Sakel, D., Vanderpump, M.P.J., Muendlein, A., Drexel, H., Fink, H.A., Ikram, M.K., Kavousi, M., Rhee, C.M., Bensenor, I.M., Azizi, F., Hankey, G.J., Iacoviello, M., Imaizumi, M., Ceresini, G., Ferrucci, L., Sgarbi, J.A., Bauer, D.C., Wareham, N., Boelaert, K., Bakker, S.J.L., Jukema, J.W., Vaes, B., Iervasi, G., Yeap, B.B., Westendorp, R.G.J., Korevaar, T.I.M., Völzke, H., Razvi, S., Gussekloo, J., Walsh, J.P., Cappola, A.R., Rodondi, N., Peeters, R.P., Chaker, L., Xu, Y.F., Derakhshan, A., Hysaj, O., Wildisen, L., Ittermann, T., Pingitore, A., Abolhassani, N., Medici, M., Kiemeney, L.A., Riksen, N.P., Dullaart, R.P.F., Trompet, S., Dörr, M., Brown, S.J., Schmidt, Börge, Führer-Sakel, D., Vanderpump, M.P.J., Muendlein, A., Drexel, H., Fink, H.A., Ikram, M.K., Kavousi, M., Rhee, C.M., Bensenor, I.M., Azizi, F., Hankey, G.J., Iacoviello, M., Imaizumi, M., Ceresini, G., Ferrucci, L., Sgarbi, J.A., Bauer, D.C., Wareham, N., Boelaert, K., Bakker, S.J.L., Jukema, J.W., Vaes, B., Iervasi, G., Yeap, B.B., Westendorp, R.G.J., Korevaar, T.I.M., Völzke, H., Razvi, S., Gussekloo, J., Walsh, J.P., Cappola, A.R., Rodondi, N., Peeters, R.P., and Chaker, L.

Abstract

Contains fulltext : 297328.pdf (Publisher’s version ) (Closed access), BACKGROUND: Reference intervals of thyroid-stimulating hormone (TSH) and free thyroxine (FT(4)) are statistically defined by the 2·5-97·5th percentiles, without accounting for potential risk of clinical outcomes. We aimed to define the optimal healthy ranges of TSH and FT(4) based on the risk of cardiovascular disease and mortality. METHODS: This systematic review and individual participant data (IPD) meta-analysis identified eligible prospective cohorts through the Thyroid Studies Collaboration, supplemented with a systematic search via Embase, MEDLINE (Ovid), Web of science, the Cochrane Central Register of Controlled Trials, and Google Scholar from Jan 1, 2011, to Feb 12, 2017 with an updated search to Oct 13, 2022 (cohorts found in the second search were not included in the IPD). We included cohorts that collected TSH or FT(4), and cardiovascular outcomes or mortality for adults (aged ≥18 years). We excluded cohorts that included solely pregnant women, individuals with overt thyroid diseases, and individuals with cardiovascular disease. We contacted the study investigators of eligible cohorts to provide IPD on demographics, TSH, FT(4), thyroid peroxidase antibodies, history of cardiovascular disease and risk factors, medication use, cardiovascular disease events, cardiovascular disease mortality, and all-cause mortality. The primary outcome was a composite outcome including cardiovascular disease events (coronary heart disease, stroke, and heart failure) and all-cause mortality. Secondary outcomes were the separate assessment of cardiovascular disease events, all-cause mortality, and cardiovascular disease mortality. We performed one-step (cohort-stratified Cox models) and two-step (random-effects models) meta-analyses adjusting for age, sex, smoking, systolic blood pressure, diabetes, and total cholesterol. The study was registered with PROSPERO, CRD42017057576. FINDINGS: We identified 3935 studies, of which 53 cohorts fulfilled the inclusion criteria and 26 co

Published
2023

16. Corrigendum to “Urinary incontinence and erectile dysfunction in patients with localized or locally advanced prostate cancer: A nationwide observational study”

Author

Vernooij, R.W.M., primary, Cremers, R.G.H.M., additional, Jansen, H., additional, Somford, D.M., additional, Kiemeney, L.A., additional, van Andel, G., additional, Wijsman, B.P., additional, Busstra, M.B., additional, van Moorselaar, R.J.A., additional, Wijnen, E.M., additional, Pos, F.J., additional, Hulshof, M.C.C.M., additional, Hamberg, P., additional, van den Berkmortel, F., additional, Hulsbergen-van de Kaa, C.A., additional, van Leenders, G.J.L.H., additional, F€utterer, J.J., additional, van Oort, I.M., additional, and Aben, K.K.H., additional

Published
2022
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17. Iam hiQ—a novel pair of accuracy indices for imputed genotypes

Author

Rosenberger, A., Tozzi, V., Bickeböller, H., Hung, R.J., Christiani, D.C., Caporaso, N.E., Liu, G., Bojesen, S.E., Le Marchand, L., Albanes, D., Aldrich, M.C., Tardon, A., Fernández-Tardón, G., Rennert, G., Field, J.K., Davies, M., Liloglou, T., Kiemeney, L.A., Lazarus, P., Haugen, A., Zienolddiny, S., Lam, S., Schabath, M.B., Andrew, A.S., Duell, E.J., Arnold, S.M., Brunnström, H., Melander, O., Goodman, G.E., Chen, C., Doherty, J.A., Teare, M.D., Cox, A., Woll, P.J., Risch, A., Muley, T.R., Johansson, M., Brennan, P., Landi, M.T., Shete, S.S., and Amos, C.I.

Abstract

Background\ud \ud Imputation of untyped markers is a standard tool in genome-wide association studies to close the gap between directly genotyped and other known DNA variants. However, high accuracy with which genotypes are imputed is fundamental. Several accuracy measures have been proposed and some are implemented in imputation software, unfortunately diversely across platforms. In the present paper, we introduce Iam hiQ, an independent pair of accuracy measures that can be applied to dosage files, the output of all imputation software. Iam (imputation accuracy measure) quantifies the average amount of individual-specific versus population-specific genotype information in a linear manner. hiQ (heterogeneity in quantities of dosages) addresses the inter-individual heterogeneity between dosages of a marker across the sample at hand.\ud \ud \ud \ud Results\ud \ud Applying both measures to a large case–control sample of the International Lung Cancer Consortium (ILCCO), comprising 27,065 individuals, we found meaningful thresholds for Iam and hiQ suitable to classify markers of poor accuracy. We demonstrate how Manhattan-like plots and moving averages of Iam and hiQ can be useful to identify regions enriched with less accurate imputed markers, whereas these regions would by missed when applying the accuracy measure info (implemented in IMPUTE2).\ud \ud \ud \ud Conclusion\ud \ud We recommend using Iam hiQ additional to other accuracy scores for variant filtering before stepping into the analysis of imputed GWAS data.

Published
2022

19. Prognostic Value of the WHO1973 and WHO2004/2016 Classification Systems for Grade in Primary Ta/T1 Non-muscle-invasive Bladder Cancer: A Multicenter European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel Study

Author

Rhijn, B.W. van, Hentschel, A.E., Bründl, J., Compérat, E.M., Hernández, V., Čapoun, O., Bruins, H.M., Cohen, D., Rouprêt, M., Shariat, S.F., Mostafid, A.H., Zigeuner, R., Dominguez-Escrig, J.L., Burger, M., Soukup, V., Gontero, P., Palou, J., Kwast, Theodorus H. van der, Heijden, A.G. van der, Kiemeney, L.A., Babjuk, M., Sylvester, R.J., Rhijn, B.W. van, Hentschel, A.E., Bründl, J., Compérat, E.M., Hernández, V., Čapoun, O., Bruins, H.M., Cohen, D., Rouprêt, M., Shariat, S.F., Mostafid, A.H., Zigeuner, R., Dominguez-Escrig, J.L., Burger, M., Soukup, V., Gontero, P., Palou, J., Kwast, Theodorus H. van der, Heijden, A.G. van der, Kiemeney, L.A., Babjuk, M., and Sylvester, R.J.

Abstract

Item does not contain fulltext, BACKGROUND: In the current European Association of Urology (EAU) non-muscle-invasive bladder cancer (NMIBC) guideline, two classification systems for grade are advocated: WHO1973 and WHO2004/2016. OBJECTIVE: To compare the prognostic value of these WHO systems. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5145 primary Ta/T1 NMIBC patients from 17 centers were collected between 1990 and 2019. The median follow-up was 3.9 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariate and multivariable analyses of WHO1973 and WHO2004/2016 stratified by center were performed for time to recurrence, progression (primary endpoint), cystectomy, and duration of survival, taking into account age, concomitant carcinoma in situ, gender, multiplicity, tumor size, initial treatment, and tumor stage. Harrell's concordance (C-index) was used for prognostic accuracy of classification systems. RESULTS AND LIMITATIONS: The median age was 68 yr; 3292 (64%) patients had Ta tumors. Neither classification system was prognostic for recurrence. For a four-tier combination of both WHO systems, progression at 5-yr follow-up was 1.4% in low-grade (LG)/G1, 3.8% in LG/G2, 7.7% in high grade (HG)/G2, and 18.8% in HG/G3 (log-rank, p < 0.001). In multivariable analyses with WHO1973 and WHO2004/2016 as independent variables, WHO1973 was a significant prognosticator of progression (p < 0.001), whereas WHO2004/2016 was not anymore (p = 0.067). C-indices for WHO1973, WHO2004, and the WHO systems combined for progression were 0.71, 0.67, and 0.73, respectively. Prognostic analyses for cystectomy and survival showed results similar to those for progression. CONCLUSIONS: In this large prognostic factor study, both classification systems were prognostic for progression but not for recurrence. For progression, the prognostic value of WHO1973 was higher than that of WHO 2004/2016. The four-tier combination (LG/G1, LG/G2, HG/G2, and HG/G3) of both WHO systems proved to be superior, as it d

Published
2021

20. Prospective bladder cancer infrastructure for experimental and observational research on bladder cancer: study protocol for the 'trials within cohorts' study ProBCI

Author

Richters, A., Meijer, R.P., Mehra, N., Boormans, J.L., Heijden, A.G. van der, Heijden, M.S. van der, Kiemeney, L.A., Aben, K.K.H., Richters, A., Meijer, R.P., Mehra, N., Boormans, J.L., Heijden, A.G. van der, Heijden, M.S. van der, Kiemeney, L.A., and Aben, K.K.H.

Abstract

Contains fulltext : 235052.pdf (Publisher’s version ) (Open Access), INTRODUCTION: A better understanding of the molecular profile of bladder tumours, the identification of novel therapeutic targets, and introduction of new drugs and has renewed research interest in the field of bladder cancer. We describe the design and setup of a Dutch Prospective Bladder Cancer Infrastructure (ProBCI) as a means to stimulate and accelerate clinically meaningful experimental and observational research. METHODS AND ANALYSIS: ProBCI entails an open cohort of patients with bladder cancer in which the trials within cohorts (TwiCs) design can be embedded. Physicians in participating hospitals prospectively recruit invasive (≥T1) patients with bladder cancer on primary diagnosis for inclusion into the study. Extensive clinical data are collected and updated every 4 months, along with patient-reported outcomes and biomaterials. Informed consent includes participation in TwiCs studies and renewed contact for future studies. Consent for participation in questionnaires and molecular analyses that may yield incidental findings is optional. ETHICS AND DISSEMINATION: The Dutch ProBCI is a unique effort to construct a nation-wide cohort of patients with bladder cancer including clinical data, patient-reported outcomes and biomaterial, to facilitate observational and experimental research. Data and materials are available for other research groups on request through www.probci.nl. Ethics approval was obtained from METC Utrecht (reference: NL70207.041.19). TRIAL REGISTRATION NUMBER: NCT04503577.

Published
2021

21. Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma

Author

Qin, N., Li, Yuancheng, Wang, Cheng, Zhu, Meng, Dai, Juncheng, Hong, Tongtong, Albanes, Demetrius, Kiemeney, L.A., Ma, Hongxia, Shen, Hongbing, Qin, N., Li, Yuancheng, Wang, Cheng, Zhu, Meng, Dai, Juncheng, Hong, Tongtong, Albanes, Demetrius, Kiemeney, L.A., Ma, Hongxia, and Shen, Hongbing

Abstract

Contains fulltext : 234989.pdf (Publisher’s version ) (Closed access)

Published
2021

22. Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers

Author

Lesseur, C., Ferreiro-Iglesias, A., McKay, J.D., Bossé, Y., Johansson, M., Gaborieau, V., Landi, M.T., Kiemeney, L.A., Hung, R.J., Brennan, P., Lesseur, C., Ferreiro-Iglesias, A., McKay, J.D., Bossé, Y., Johansson, M., Gaborieau, V., Landi, M.T., Kiemeney, L.A., Hung, R.J., and Brennan, P.

Abstract

Contains fulltext : 231563.pdf (publisher's version ) (Open Access)

Published
2021

23. Measurement and genetic architecture of lifetime depression in the Netherlands as assessed by LIDAS (Lifetime Depression Assessment Self-report)

Author

Fedko, Iryna O., Hottenga, Jouke-Jan, Helmer, Quinta, Mbarek, Hamdi, Huider, Floris, Amin, Najaf, Galesloot, T.E., Kiemeney, L.A., Boomsma, D.I., Bot, Mariska, Fedko, Iryna O., Hottenga, Jouke-Jan, Helmer, Quinta, Mbarek, Hamdi, Huider, Floris, Amin, Najaf, Galesloot, T.E., Kiemeney, L.A., Boomsma, D.I., and Bot, Mariska

Abstract

Item does not contain fulltext

Published
2021

25. European Association of Urology (EAU) Prognostic Factor Risk Groups for Non-muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel

Author

Sylvester, R.J., Rodríguez, O., Hernández, V., Turturica, D., Bauerová, L., Bruins, H.M., Bründl, J., Kwast, Theodorus H. van der, Brisuda, A., Rubio-Briones, J., Seles, M., Hentschel, A.E., Kusuma, V.R.M., Huebner, N., Cotte, J., Mertens, L.S., Volanis, D., Cussenot, O., Henríquez, J.D. Subiela, Peña, E. de la, Pisano, F., Pešl, M., Heijden, A.G. van der, Herdegen, S., Zlotta, A.R., Hacek, J., Calatrava, A., Mannweiler, S., Bosschieter, J., Ashabere, D., Haitel, A., Côté, J.F., Sheikh, S., Lunelli, L., Algaba, F., Alemany, I., Soria, F., Runneboom, W., Breyer, J., Nieuwenhuijzen, J.A., Llorente, C., Molinaro, L., Hulsbergen-van de Kaa, C.A., Evert, M., Kiemeney, L.A., N'Dow, J., Plass, K., Čapoun, O., Soukup, V., Dominguez-Escrig, J.L., Cohen, D., Palou, J., Gontero, P., Burger, M., Zigeuner, R., Mostafid, A.H., Shariat, S.F., Rouprêt, M., Compérat, E.M., Babjuk, M., Rhijn, B.W. van, Sylvester, R.J., Rodríguez, O., Hernández, V., Turturica, D., Bauerová, L., Bruins, H.M., Bründl, J., Kwast, Theodorus H. van der, Brisuda, A., Rubio-Briones, J., Seles, M., Hentschel, A.E., Kusuma, V.R.M., Huebner, N., Cotte, J., Mertens, L.S., Volanis, D., Cussenot, O., Henríquez, J.D. Subiela, Peña, E. de la, Pisano, F., Pešl, M., Heijden, A.G. van der, Herdegen, S., Zlotta, A.R., Hacek, J., Calatrava, A., Mannweiler, S., Bosschieter, J., Ashabere, D., Haitel, A., Côté, J.F., Sheikh, S., Lunelli, L., Algaba, F., Alemany, I., Soria, F., Runneboom, W., Breyer, J., Nieuwenhuijzen, J.A., Llorente, C., Molinaro, L., Hulsbergen-van de Kaa, C.A., Evert, M., Kiemeney, L.A., N'Dow, J., Plass, K., Čapoun, O., Soukup, V., Dominguez-Escrig, J.L., Cohen, D., Palou, J., Gontero, P., Burger, M., Zigeuner, R., Mostafid, A.H., Shariat, S.F., Rouprêt, M., Compérat, E.M., Babjuk, M., and Rhijn, B.W. van

Abstract

Item does not contain fulltext, BACKGROUND: The European Association of Urology (EAU) prognostic factor risk groups for non-muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT). They do not, however, take into account the widely used World Health Organization (WHO) 2004/2016 grading classification and are based on patients treated in the 1980s. OBJECTIVE: To update EAU prognostic factor risk groups using the WHO 1973 and 2004/2016 grading classifications and identify patients with the lowest and highest probabilities of progression. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for primary NMIBC patients were collected from the institutions of the members of the EAU NMIBC guidelines panel. INTERVENTION: Patients underwent TURBT followed by intravesical instillations at the physician's discretion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable Cox proportional-hazards regression models were fitted to the primary endpoint, the time to progression to muscle-invasive disease or distant metastases. Patients were divided into four risk groups: low-, intermediate-, high-, and a new, very high-risk group. The probabilities of progression were estimated using Kaplan-Meier curves. RESULTS AND LIMITATIONS: A total of 3401 patients treated with TURBT ± intravesical chemotherapy were included. From the multivariable analyses, tumor stage, WHO 1973/2004-2016 grade, concomitant carcinoma in situ, number of tumors, tumor size, and age were used to form four risk groups for which the probability of progression at 5 yr varied from <1% to >40%. Limitations include the retrospective collection of data and the lack of central pathology review. CONCLUSIONS: This study provides updated EAU prognostic factor risk groups that can be used to inform patient treatment and follow-up. Incorporating the WHO 2004/2016 and 1973 grading classifications, a new, very high-risk group has been identified for wh

Published
2021

28. Menstrual factors, reproductive history, hormone use, and urothelial carcinoma risk: a prospective study in the EPIC cohort

Author

Lujan-Barroso, L. Botteri, E. Caini, S. Ljungberg, B.F. Roswall, N. Tjønneland, A. Bueno-De-Mesquita, B. Gram, I.T. Tumino, R. Kiemeney, L.A. Liedberg, F. Stocks, T. Gunter, M.J. Murphy, N. Cervenka, I. Fournier, A. Kvaskoff, M. Haggstrom, C. Overvad, K. Lund, E. Waaseth, M. Fortner, R.T. Kuhn, T. Menendez, V. Sanchez, M.-J. Santiuste, C. Perez-Cornago, A. Zamora-Ros, R. Cross, A.J. Trichopoulou, A. Karakatsani, A. Peppa, E. Palli, D. Krogh, V. Sciannameo, V. Mattiello, A. Panico, S. van Gils, C.H. Charlotte Onland-Moret, N. Barricarte, A. Amiano, P. Khaw, K.-T. Boeing, H. Weiderpass, E. Duell, E.J.

Abstract

Background: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk. Methods: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non–muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models. Results: During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with urothelial carcinoma risk (HR≥5vs1 ¼ 0.48; 0.25–0.90; Ptrend in parous women ¼ 0.010) and MHT use (compared with nonuse) was positively associated with urothelial carcinoma risk (HR ¼ 1.27; 1.03–1.57), but no dose response by years of MHT use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analyses in never smokers showed similar HR patterns for the number of FTP, while no association between MHT use and urothelial carcinoma risk was observed. Association between MHT use and urothelial carcinoma risk remained significant only in current smokers. No heterogeneity of the risk estimations in the final model was observed by tumor aggressiveness or by tumor grade. A positive association between MTH use and non–muscle-invasive urothelial carcinoma risk was observed. Conclusions: Our results support that increasing the number of FTP may reduce urothelial carcinoma risk. Impact: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells. © 2020 American Association for Cancer Research.

Published
2020

29. Menstrual Factors, Reproductive History, Hormone Use, and Urothelial Carcinoma Risk: AProspective Study in the EPIC Cohort

Author

Lujan-Barroso, Leila, Botteri, Edoardo, Caini, S., Ljungberg, B., Roswall, N., Tjonneland, A., Kiemeney, L.A., Weiderpass, E., Duell, Eric J., Lujan-Barroso, Leila, Botteri, Edoardo, Caini, S., Ljungberg, B., Roswall, N., Tjonneland, A., Kiemeney, L.A., Weiderpass, E., and Duell, Eric J.

Abstract

Contains fulltext : 223767.pdf (Publisher’s version ) (Closed access)

Published
2020

31. Insight into bladder cancer care: study protocol of a large nationwide prospective cohort study (BlaZIB)

Author

Ripping, T.M., Kiemeney, L.A., Hoogstraten, L.M.C. van, Witjes, J.A., Aben, K.K.H., Ripping, T.M., Kiemeney, L.A., Hoogstraten, L.M.C. van, Witjes, J.A., and Aben, K.K.H.

Abstract

Contains fulltext : 220668.pdf (publisher's version ) (Open Access), BACKGROUND: Despite the embedding of bladder cancer management in European guidelines, large variation in clinical practice exists for applied diagnostics and treatments. This variation may affect patients' outcomes including complications, disease recurrence, progression, survival, and health-related quality of life (HRQL). Lack of detailed clinical data and HRQL data hampers a comprehensive evaluation of bladder cancer care. Through prospective data registration, this study aims to provide insight in bladder cancer care in the Netherlands and to identify barriers and modulators of optimal bladder cancer care. METHODS: This study is a nationwide prospective cohort study including all patients who were newly diagnosed with high-risk non-muscle invasive bladder cancer (HR-NMIBC; Tis and/or T1, N0, M0/x) or non-metastatic muscle invasive bladder cancer (MIBC; >/=T2, N0/x-3, M0/x) in the Netherlands between November 1st 2017 and October 31st 2019. Extensive data on patient- and tumor characteristics, diagnostics, treatment and follow-up up to 2 years after diagnosis will be collected prospectively from electronic health records in the participating hospitals by data managers of the Netherlands Cancer Registry (NCR). Additionally, patients will be requested to participate in a HRQL survey shortly after diagnosis and subsequently at 6, 12 and 24 months. The HRQL survey includes six standardized questionnaires, e.g. SCQ Comorbidity score, EQ-5D-5 L, EORTC-QLQ-C30, EORTC-QLQ-BLM30, EORTC-QLQ-NMIBC24 and BCI. Variation in care and deviation from the European guidelines will be assessed through descriptive analyses and multivariable multilevel analyses. Survival analyses will be used to assess the association between variation in care and relevant outcomes such as survival. DISCUSSION: The results of this observational study will guide modifications of clinical practice and/or adaptation of guidelines and may set the agenda for new specific research questions in the manageme

Published
2020

32. Association Analysis of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci with 20,871 Lung Cancer Cases and 15,971 Controls

Author

Wang, Yuzhuo, Gorlova, Olga Y., Gorlov, I., Zhu, M., Dai, J., Albanes, Demetrius, Kiemeney, L.A., Amos, C.I., Shen, H., Wang, Yuzhuo, Gorlova, Olga Y., Gorlov, I., Zhu, M., Dai, J., Albanes, Demetrius, Kiemeney, L.A., Amos, C.I., and Shen, H.

Abstract

Contains fulltext : 221428.pdf (Publisher’s version ) (Closed access)

Published
2020

34. Hospital-specific probability of cystectomy affects survival from muscle-invasive bladder cancer

Author

Ripping, T.M., Witjes, J.A., Meijer, R.P., Rhijn, B.W. van, Oddens, J.R., Goossens-Laan, C.A., Mulder, S.F., Moorselaar, R.J.A. van, Kiemeney, L.A., Aben, K.K.H., Ripping, T.M., Witjes, J.A., Meijer, R.P., Rhijn, B.W. van, Oddens, J.R., Goossens-Laan, C.A., Mulder, S.F., Moorselaar, R.J.A. van, Kiemeney, L.A., and Aben, K.K.H.

Abstract

Contains fulltext : 229162.pdf (Publisher’s version ) (Closed access), OBJECTIVES: Radical cystectomies (RCs) are increasingly centralized, but bladder cancer can be diagnosed in every hospital The aim of this study is to assess the variation between hospitals of diagnosis in a patient's chance to undergo a RC before and after the volume criteria for RCs, to identify factors associated with this variation and to assess its effect on survival. METHODS AND MATERIALS: Patients diagnosed with muscle-invasive bladder cancer (cT2-4a,N0/X,M0/X) without nodal or distant metastases between 2008 and 2016 were identified through the Netherlands Cancer Registry. Multilevel logistic regression analysis was used to investigate the hospital specific probability of undergoing a cystectomy. Cox proportional hazard regression analysis was used to assess the case-mix adjusted effect of hospital-specific probabilities on survival. RESULTS: Of the 9,215 included patients, 4,513 (49%) underwent a RC. The percentage of RCs varied between 7% and 83% by hospital of diagnosis before the introduction of the first volume criteria (i.e., 2008-2009; minimum of 10 RCs). This variation decreased slightly to 17%-77% after establishment of the second volume criteria (i.e., 2015-2016; minimum of 20 RCs). Age, cT-stage and comorbidity were inversely and socioeconomic status was positively associated with RC. Both being diagnosed in a community hospital and/or being diagnosed in a hospital fulfilling the RC volume criteria were associated with increased use of RC compared to academic hospitals and hospitals not fulfilling the volume criteria. For each 10% increase in the percentage of RC in the hospital of diagnosis, 2-year case-mix adjusted survival increased 4% (hazard ratio 0.96, 95% confidence interval 0.94-0.98). CONCLUSION: Probability of RC varied between hospitals of diagnosis and affected 2-year overall survival. Undergoing a RC was associated with age, cT-stage, socioeconomic status, type of hospital, and whether the hospital of diagnosis fulfilled the RC volume

Published
2020

35. Identification of ADHD risk genes in extended pedigrees by combining linkage analysis and whole-exome sequencing

Author

Corominas, J., Klein, M., Zayats, T., Rivero, O., Ziegler, G.C., Pauper, M., Neveling, Kornelia, Poelmans, G.J.V., Arias Vasquez, A., Galesloot, T.E., Kiemeney, L.A., Buitelaar, J.K., Franke, B., Lesch, Klaus-Peter, Corominas, J., Klein, M., Zayats, T., Rivero, O., Ziegler, G.C., Pauper, M., Neveling, Kornelia, Poelmans, G.J.V., Arias Vasquez, A., Galesloot, T.E., Kiemeney, L.A., Buitelaar, J.K., Franke, B., and Lesch, Klaus-Peter

Abstract

Contains fulltext : 223478.pdf (publisher's version ) (Open Access)

Published
2020

36. GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer

Author

Zhou, W. (Wei), Brumpton, B. (Ben), Kabil, O. (Omer), Gudmundsson, J. (Julius), Thorleifsson, G. (Gudmar), Weinstock, J. (Josh), Zawistowski, M. (Matthew), Nielsen, J.B. (Jonas B.), Chaker, L. (Layal), Medici, M. (Marco), Teumer, A. (Alexander), Naitza, S. (Silvia), Sanna, S. (Serena), Schultheiss, U.T. (Ulla T.), Cappola, A.R. (Anne), Karjalainen, J. (Juha), Kurki, M. (Mitja), Oneka, M. (Morgan), Taylor, P.N. (Peter N.), Fritsche, L.G. (Lars), Graham, S.E. (Sarah E.), Wolford, B.N. (Brooke N.), Overton, W. (William), Rasheed, H. (Humaira), Haug, E.B. (Eirin B.), Gabrielsen, M.E. (Maiken Elvestad), Skogholt, A.H. (Anne Heidi), Surakka, I. (Ida), Davey Smith, G. (George), Pandit, A. (Anita), Roychowdhury, T. (Tanmoy), Hornsby, W.E. (Whitney E.), Jonasson, J.G. (Jon G.), Senter, L. (Leigha), Liyanarachchi, S. (Sandya), Ringel, M.D. (Matthew D.), Xu, L. (Li), Kiemeney, L.A. (Lambertus A.), He, H. (Hao), Netea-Maier, R.T. (Romana), Mayordomo, J.I. (José), Plantinga, T.S. (Theo S.), Hrafnkelsson, J. (Jon), Hjartarson, H. (Hannes), Sturgis, E.M. (Erich M.), Palotie, A. (Aarno), Daly, M.J. (Mark), Citterio, C.E. (Cintia E.), Arvan, P. (Peter), Brummett, C.M. (Chad M.), Boehnke, M. (Michael), La Chapelle, A. (Albert) de, Stefansson, K. (Kari), Hveem, K. (Kristian), Willer, C.J. (Cristen), Asvold, B.O. (Bjorn O.), Zhou, W. (Wei), Brumpton, B. (Ben), Kabil, O. (Omer), Gudmundsson, J. (Julius), Thorleifsson, G. (Gudmar), Weinstock, J. (Josh), Zawistowski, M. (Matthew), Nielsen, J.B. (Jonas B.), Chaker, L. (Layal), Medici, M. (Marco), Teumer, A. (Alexander), Naitza, S. (Silvia), Sanna, S. (Serena), Schultheiss, U.T. (Ulla T.), Cappola, A.R. (Anne), Karjalainen, J. (Juha), Kurki, M. (Mitja), Oneka, M. (Morgan), Taylor, P.N. (Peter N.), Fritsche, L.G. (Lars), Graham, S.E. (Sarah E.), Wolford, B.N. (Brooke N.), Overton, W. (William), Rasheed, H. (Humaira), Haug, E.B. (Eirin B.), Gabrielsen, M.E. (Maiken Elvestad), Skogholt, A.H. (Anne Heidi), Surakka, I. (Ida), Davey Smith, G. (George), Pandit, A. (Anita), Roychowdhury, T. (Tanmoy), Hornsby, W.E. (Whitney E.), Jonasson, J.G. (Jon G.), Senter, L. (Leigha), Liyanarachchi, S. (Sandya), Ringel, M.D. (Matthew D.), Xu, L. (Li), Kiemeney, L.A. (Lambertus A.), He, H. (Hao), Netea-Maier, R.T. (Romana), Mayordomo, J.I. (José), Plantinga, T.S. (Theo S.), Hrafnkelsson, J. (Jon), Hjartarson, H. (Hannes), Sturgis, E.M. (Erich M.), Palotie, A. (Aarno), Daly, M.J. (Mark), Citterio, C.E. (Cintia E.), Arvan, P. (Peter), Brummett, C.M. (Chad M.), Boehnke, M. (Michael), La Chapelle, A. (Albert) de, Stefansson, K. (Kari), Hveem, K. (Kristian), Willer, C.J. (Cristen), and Asvold, B.O. (Bjorn O.)

Abstract

Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. To better understand the genetic contribution to TSH levels, we conduct a GWAS meta-analysis at 22.4 million genetic markers in up to 119,715 individuals and identify 74 genome-wide significant loci for TSH, of which 28 are previously unreported. Functional experiments show that the thyroglobulin protein-altering variants P118L and G67S impact thyroglobulin secretion. Phenome-wide association analysis in the UK Biobank demonstrates the pleiotropic effects of TSH-associated variants and a polygenic score for higher TSH levels is associated with a reduced risk of thyroid cancer in the UK Biobank and three other independent studies. Two-sample Mendelian randomization using TSH index variants as instrumental variables suggests a protective effect of higher TSH levels (indicating lower thyroid function) on risk of thyroid cancer and goiter. Our findings highlight the pleiotropic effects of TSH-associated variants on thyroid function and growth of malignant and benign thyroid tumors.

Published
2020
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37. Measurement and genetic architecture of lifetime depression in the Netherlands as assessed by LIDAS (Lifetime Depression Assessment Self-report)

Author

Fedko, I.O. (Iryna O.), Hottenga, J.J. (Jouke Jan), Helmer, Q. (Quinta), Mbarek, H., Huider, F. (Floris), Amin, N. (Najaf), Beulens, J.W.J. (Joline), Bremmer, M.A. (Marijke A.), Elders, P.J.M. (Petra), Galesloot, T.E. (Tessel), Kiemeney, L.A. (Lambertus A.), Van Loo, H.M. (Hanna M.), Picavet, H.S.J. (H. Susan J.), Rutters, F. (Femke), Spek, A. (Ashley) van der, Van De Wiel, A.M. (Anne M.), Duijn, C.M. (Cornelia) van, Geus, E.J.C. (Eco) de, Feskens, E.J.M. (Edith), Hartman, C.A. (Catharina A.), Oldehinkel, A.J. (Albertine J.), Smit, J.H. (Jan H.), Verschuren, W.M.M. (W. M. Monique), Penninx, B.W.J.H. (Brenda), Boomsma, D.I. (Dorret), Essink-Bot, M.L.E. (Marie-Louise), Fedko, I.O. (Iryna O.), Hottenga, J.J. (Jouke Jan), Helmer, Q. (Quinta), Mbarek, H., Huider, F. (Floris), Amin, N. (Najaf), Beulens, J.W.J. (Joline), Bremmer, M.A. (Marijke A.), Elders, P.J.M. (Petra), Galesloot, T.E. (Tessel), Kiemeney, L.A. (Lambertus A.), Van Loo, H.M. (Hanna M.), Picavet, H.S.J. (H. Susan J.), Rutters, F. (Femke), Spek, A. (Ashley) van der, Van De Wiel, A.M. (Anne M.), Duijn, C.M. (Cornelia) van, Geus, E.J.C. (Eco) de, Feskens, E.J.M. (Edith), Hartman, C.A. (Catharina A.), Oldehinkel, A.J. (Albertine J.), Smit, J.H. (Jan H.), Verschuren, W.M.M. (W. M. Monique), Penninx, B.W.J.H. (Brenda), Boomsma, D.I. (Dorret), and Essink-Bot, M.L.E. (Marie-Louise)

Abstract

BackgroundMajor depressive disorder (MDD) is a common mood disorder, with a heritability of around 34%. Molecular genetic studies mad

Published
2020
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38. Contribution of Intellectual Disability-Related Genes to ADHD Risk and to Locomotor Activity in Drosophila

Author

Klein, M., Singgih, E.L., Rens, A.B. van, Demontis, Ditte, Borglum, Anders D., Roth Mota, N., Castells Nobau, A., Kiemeney, L.A., Brunner, H.G., Arias Vasquez, A., Schenck, A., Voet, M. van der, Franke, B., Klein, M., Singgih, E.L., Rens, A.B. van, Demontis, Ditte, Borglum, Anders D., Roth Mota, N., Castells Nobau, A., Kiemeney, L.A., Brunner, H.G., Arias Vasquez, A., Schenck, A., Voet, M. van der, and Franke, B.

Abstract

Contains fulltext : 219830.pdf (Publisher’s version ) (Closed access)

Published
2020

40. 763P The influence of multidisciplinary team meetings on treatment decisions in muscle invasive bladder cancer: A nationwide study in the Netherlands

Author

Walraven, J.E.W., primary, Ripping, T.M., additional, Oddens, J.R., additional, van Rhijn, B.W.G., additional, Goossens-Laan, C.A., additional, Hulshof, M.C.C.M., additional, BlaZIB, S.G., additional, Kiemeney, L.A., additional, Witjes, J.A., additional, Aben, K.K.H., additional, Lemmens, V.E.P.P., additional, van der Hoeven, J.J.M., additional, Desar, I.M.E., additional, and Verhoeven, R.H.A., additional

Published
2020
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41. Urinary incontinence and erectile dysfunction in patients with localized or locally advanced prostate cancer: A nationwide observational study

Author

Vernooij, R.W.M., primary, Cremers, R.G.H.M., additional, Jansen, H., additional, Somford, D.M., additional, Kiemeney, L.A., additional, van Andel, G., additional, Wijsman, B.P., additional, Busstra, M.B., additional, van Moorselaar, R.J.A., additional, Wijnen, E.M., additional, Pos, F.J., additional, Hulshof, M.C.C.M., additional, Hamberg, P., additional, van den Berkmortel, F., additional, Hulsbergen-van de Kaa, C.A., additional, van Leenders, G.J.L.H., additional, Fütterer, J.J., additional, van Oort, I.M., additional, and Aben, K.K.H., additional

Published
2020
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42. Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers

Author

van der Post, R.S., Kiemeney, L.A., Ligtenberg, M.J.L., Witjes, J.A., Hulsbergen-van de Kaa, C.A., Bodmer, D., Schaap, L., Kets, C.M., van Krieken, J.H.J.M., and Hoogerbrugge, N.

Subjects
Bladder cancer -- Risk factors, Bladder cancer -- Genetic aspects, Bladder cancer -- Research, Colorectal cancer -- Genetic aspects, Colorectal cancer -- Research, DNA mismatch repair -- Research, Health
Published
2010

43. Shared heritability and functional enrichment across six solid cancers (vol 10, 431, 2019)

Author

Jiang, X., Finucane, H.K., Schumacher, F.R., Schmit, S.L., Tyrer, J.P., Han, Y., Michailidou, K., Lesseur, C., Kuchenbaecker, K.B., Dennis, J., Conti, D.V., Casey, G., Gaudet, M.M., Huyghe, J.R., Albanes, D., Aldrich, M.C., Andrew, A.S., Andrulis, I.L., Anton-Culver, H., Antoniou, A.C., Antonenkova, N.N., Arnold, S.M., Aronson, K.J., Arun, B.K., Bandera, E.V., Barkardottir, R.B., Barnes, D.R., Batra, J., Beckmann, M.W., Benitez, J., Benlloch, S., Berchuck, A., Berndt, S.I., Bickeboller, H., Bien, S.A., Blomqvist, C., Boccia, S., Bogdanova, N.V., Bojesen, S.E., Bolla, M.K., Brauch, H., Brenner, H., Brenton, J.D., Brook, M.N., Brunet, J., Brunnstrom, H., Buchanan, D.D., Burwinkel, B., Butzow, R., Cadoni, G., Caldes, T., Caligo, M.A., Campbell, I., Campbell, P.T., Cancel-Tassin, G., Cannon-Albright, L., Campa, D., Caporaso, N., Carvalho, A.L., Chan, A.T., Chang-Claude, J., Chanock, S.J., Chen, C., Christiani, D.C., Claes, K.B.M., Claessens, F., Clements, J., Collee, J.M., Correa, M.C., Couch, F.J., Cox, A., Cunningham, J.M., Cybulski, C., Czene, K., Daly, M.B., deFazio, A., Devilee, P., Diez, O., Gago-Dominguez, M., Donovan, J.L., Dork, T., Duell, E.J., Dunning, A.M., Dwek, M., Eccles, D.M., Edlund, C.K., Edwards, D.R.V., Ellberg, C., Evans, D.G., Fasching, P.A., Ferris, R.L., Liloglou, T., Figueiredo, J.C., Fletcher, O., Fortner, R.T., Fostira, F., Franceschi, S., Friedman, E., Gallinger, S.J., Ganz, P.A., Garber, J., Garcia-Saenz, J.A., Gayther, S.A., Giles, G.G., Godwin, A.K., Goldberg, M.S., Goldgar, D.E., Goode, E.L., Goodman, M.T., Goodman, G., Grankvist, K., Greene, M.H., Gronberg, H., Gronwald, J., Guenel, P., Hakansson, N., Hall, P., Hamann, U., Hamdy, F.C., Hamilton, R.J., Hampe, J., Haugen, A., Heitz, F., Herrero, R., Hillemanns, P., Hoffmeister, M., Hogdall, E., Hong, Y.C., Hopper, J.L., Houlston, R., Hulick, P.J., Hunter, D.J., Huntsman, D.G., Idos, G., Imyanitov, E.N., Ingles, S.A., Isaacs, C., Jakubowska, A., James, P., Jenkins, M.A., Johansson, M., John, E.M., Joshi, A.D., Kaneva, R., Karlan, B.Y., Kelemen, L.E., Kuhl, T., Khaw, K.T., Khusnutdinova, E., Kibel, A.S., Kiemeney, L.A., Kim, J., Kjaer, S.K., Knight, J.A., Kogevinas, M., Kote-Jarai, Z., Koutros, S., Kristensen, V.N., Kupryjanczyk, J., Lacko, M., Lam, S., Lambrechts, D., Landi, M.T., Lazarus, P., N.D. le, Lee, E., Lejbkowicz, F., Lenz, H.J., Leslie, G., Lessel, D., Lester, J., Levine, D.A., Li, L., Li, C.I., Lindblom, A., Lindor, N.M., Liu, G., Loupakis, F., Lubinski, J., Maehle, L., Maier, C., Mannermaa, A., Marchand, L., Margolin, S., May, T., McGuffog, L., Meindl, A., Middha, P., Miller, A., Milne, R.L., MacInnis, R.J., Modugno, F., Montagna, M., Moreno, V., Moysich, K.B., Mucci, L., Muir, K., Mulligan, A.M., Nathanson, K.L., Neal, D.E., Ness, A.R., Neuhausen, S.L., Nevanlinna, H., Newcomb, P.A., Newcomb, L.F., Nielsen, F.C., Nikitina-Zake, L., Nordestgaard, B.G., Nussbaum, R.L., Offit, K., Olah, E., Olama, A.A. al, Olopade, O.I., Olshan, A.F., Olsson, H., Osorio, A., Pandha, H., Park, J.Y., Pashayan, N., Parsons, M.T., Pejovic, T., Penney, K.L., Peters, W.H.M., Phelan, C.M., Phipps, A.I., Plaseska-Karanfilska, D., Pring, M., Prokofyeva, D., Radice, P., Stefansson, K., Ramus, S.J., Raskin, L., Rennert, G., Rennert, H.S., Rensburg, E.J., Riggan, M.J., Risch, H.A., Risch, A., Roobol, M.J., Rosenstein, B.S., Rossing, M.A., Ruyck, K., Saloustros, E., Sandler, D.P., Sawyer, E.J., Schabath, M.B., Schleutker, J., Schmidt, M.K., Setiawan, V.W., Shen, H.B., Siegel, E.M., Sieh, W., Singer, C.F., Slattery, M.L., Sorensen, K.D., Southey, M.C., Spurdle, A.B., Stanford, J.L., Stevens, V.L., Stintzing, S., Stone, J., Sundfeldt, K., Sutphen, R., Swerdlow, A.J., Tajara, E.H., Tangen, C.M., Tardon, A., Taylor, J.A., Teare, M.D., Teixeira, M.R., Terry, M.B., Terry, K.L., Thibodeau, S.N., Thomassen, M., Bjorge, L., Tischkowitz, M., Toland, A.E., Torres, D., Townsend, P.A., Travis, R.C., Tung, N., and Tworoger

Published
2019

44. [The relationship between lifestyle and cancer; topic of conversation in the consultation room?]

Author

Swankhuisen, C.E., Evers, J., Kiemeney, L.A., Hoogerbrugge, N., and Vegt, F. de

Subjects
Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Other Research Radboud Institute for Health Sciences [Radboudumc 0], education, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14]
Abstract

Item does not contain fulltext OBJECTIVE: This survey explores the degree of consensus amongst healthcare professionals for the support of cancer patients' lifestyle management, based on three questions posed to them: a) what do they know about the relation between lifestyle and cancer?; b) do they consider lifestyle support for cancer patients part of their professional role?; c) does their own lifestyle influence the lifestyle management consultations they may have with cancer patients? Design Survey study. METHOD: A digital questionnaire with questions concerning lifestyle and cancer was sent to 1550 healthcare professionals in and around Nijmegen. The questionnaire was filled out by 562 healthcare professionals (36% response rate), of whom 404 (72%) were involved in cancer patient care. This cohort of responders consisted of 170 medical specialists, 62 general practitioners, and 172 nurses and allied health professionals. RESULTS: Healthcare professionals acknowledge the influence of lifestyle on the development of cancer. Almost all healthcare professionals (98%) agree on the positive effects of a healthy lifestyle on the well-being of cancer patients. Approximately two-thirds of all responders believe that lifestyle support should 'usually' or 'always' form part of cancer care; about fifty percent report to implement this in clinical practice. Healthcare professionals require evidence-based knowledge concerning the relationship between lifestyle and cancer, patient information materials, and additional consultation time to support lifestyle management involving cancer patients. The healthcare professionals' own lifestyle appears to have an influence: in those responders who do not adhere to a healthy lifestyle themselves, lifestyle was also covered less in consultations. CONCLUSION: This explorative survey shows that lifestyle support of cancer patients is deemed an important topic amongst healthcare professionals.

Published
2019

45. Mendelian Randomization and mediation analysis of leukocyte telomere length and risk of lung and head and neck cancers

Author

Kachuri, L. Saarela, O. Bojesen, S.E. Davey Smith, G. Liu, G. Landi, M.T. Caporaso, N.E. Christiani, D.C. Johansson, M. Panico, S. Overvad, K. Trichopoulou, A. Vineis, P. Scelo, G. Zaridze, D. Wu, X. Albanes, D. Diergaarde, B. Lagiou, P. Macfarlane, G.J. Aldrich, M.C. Tardón, A. Rennert, G. Olshan, A.F. Weissler, M.C. Chen, C. Goodman, G.E. Doherty, J.A. Ness, A.R. Bickeböller, H. Wichmann, H.-E. Risch, A. Field, J.K. Teare, M.D. Kiemeney, L.A. Van Der Heijden, E.H.F.M. Carroll, J.C. Haugen, A. Zienolddiny, S. Skaug, V. Wünsch-Filho, V. Tajara, E.H. Ayoub Moysés, R. Daumas Nunes, F. Lam, S. Eluf-Neto, J. Lacko, M. Peters, W.H.M. Le Marchand, L. Duell, E.J. Andrew, A.S. Franceschi, S. Schabath, M.B. Manjer, J. Arnold, S. Lazarus, P. Mukeriya, A. Swiatkowska, B. Janout, V. Holcatova, I. Stojsic, J. Mates, D. Lissowska, J. Boccia, S. Lesseur, C. Zong, X. McKay, J.D. Brennan, P. Amos, C.I. Hung, R.J.

Abstract

Background: Evidence from observational studies of telomere length (TL) has been conflicting regarding its direction of association with cancer risk. We investigated the causal relevance of TL for lung and head and neck cancers using Mendelian Randomization (MR) and mediation analyses. Methods: We developed a novel genetic instrument for TL in chromosome 5p15.33, using variants identified through deep-sequencing, that were genotyped in 2051 cancer-free subjects. Next, we conducted an MR analysis of lung (16 396 cases, 13 013 controls) and head and neck cancer (4415 cases, 5013 controls) using eight genetic instruments for TL. Lastly, the 5p15.33 instrument and distinct 5p15.33 lung cancer risk loci were evaluated using two-sample mediation analysis, to quantify their direct and indirect, telomere-mediated, effects. Results: The multi-allelic 5p15.33 instrument explained 1.49-2.00% of TL variation in our data (p = 2.6 × 10-9). The MR analysis estimated that a 1000 base-pair increase in TL increases risk of lung cancer [odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.20-1.65] and lung adenocarcinoma (OR = 1.92, 95% CI: 1.51-2.22), but not squamous lung carcinoma (OR = 1.04, 95% CI: 0.83-1.29) or head and neck cancers (OR = 0.90, 95% CI: 0.70-1.05). Mediation analysis of the 5p15.33 instrument indicated an absence of direct effects on lung cancer risk (OR = 1.00, 95% CI: 0.95-1.04). Analysis of distinct 5p15.33 susceptibility variants estimated that TL mediates up to 40% of the observed associations with lung cancer risk. Conclusions: Our findings support a causal role for long telomeres in lung cancer aetiology, particularly for adenocarcinoma, and demonstrate that telomere maintenance partially mediates the lung cancer susceptibility conferred by 5p15.33 loci. © 2018 The Author(s) 2018; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Published
2019

46. Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers

Author

Page, Elizabeth C., Bancroft, Elizabeth K., Brook, Mark N., Assel, M., Battat, Mona Hassan Al, Thomas, S.L., Kiemeney, L.A., Zelst-Stams, W.A.G. van, Lilja, Hans, Eeles, R.A., Clinical Genetics, and Urology

Subjects
All institutes and research themes of the Radboud University Medical Center, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

Contains fulltext : 212399.pdf (Publisher’s version ) (Closed access)

Published
2019

48. Immediate treatment vs. active-surveillance in very-low-risk prostate cancer: the role of patient-, tumour-, and hospital-related factors

Author

Jansen, Hanneke, Oort, I.M. van, Andel, George van, Wijsman, Bart P., Pos, Floris J., Hulshof, Maarten C.C.M., Hulsbergen-van de Kaa, C.A., Futterer, J.J., Kiemeney, L.A., Aben, K.K.H., Jansen, Hanneke, Oort, I.M. van, Andel, George van, Wijsman, Bart P., Pos, Floris J., Hulshof, Maarten C.C.M., Hulsbergen-van de Kaa, C.A., Futterer, J.J., Kiemeney, L.A., and Aben, K.K.H.

Abstract

Contains fulltext : 203877.pdf (publisher's version ) (Closed access)

Published
2019

50. Genome-wide Association Study for Tumour Stage, Grade, Size, and Age at Diagnosis of Non-muscle-invasive Bladder Cancer

Author

Lipunova, N., Wesselius, A., Cheng, K.K., Schooten, F.J. van, Bryan, R.T., Cazier, J.B., Galesloot, T.E., Kiemeney, L.A., Zeegers, M.P., Lipunova, N., Wesselius, A., Cheng, K.K., Schooten, F.J. van, Bryan, R.T., Cazier, J.B., Galesloot, T.E., Kiemeney, L.A., and Zeegers, M.P.

Abstract

Item does not contain fulltext, BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) causes a considerable health burden due to the high recurrence and progression rates. Past studies have identified multiple candidate loci associated with NMIBC prognosis, albeit lacking validation. Moreover, scarce reports exist on genetic susceptibility to independent prognostic predictors of NMIBC, such as stage or grade. OBJECTIVE: To investigate genetic associations with NMIBC tumour and patient characteristics at the time of diagnosis. DESIGN, SETTING, AND PARTICIPANTS: A sample of 653 NMIBC cases comes from the Bladder Cancer Prognosis Programme. Replication of the significant findings was conducted in the Nijmegen Bladder Cancer Study cohort (N=1470). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A genome-wide association study (GWAS) was carried out for outcomes of tumour size (as a continuous variable in centimetres), stage (Tis and T1 vs Ta), grade (G3 vs G2 and G1), and age (as continuous [years] and dichotomous [70.2 yr as a cut-off] variables). RESULTS AND LIMITATIONS: Significant (p<5E-08) associations (N=61) with tumour size, stage, grade, and age were identified in the GWAS discovery stage. None of the variants were independently significantly associated in the replication cohort. A meta-analysis of both cohorts suggests that rs180940944 (13q13.3 locus, NBEA) was associated with tumour size as a continuous variable (ss=0.9cm, p=2.92E-09). However, other single nucleotide polymorphisms in this region did not show evidence of association in the meta-analysis. CONCLUSIONS: Our study suggests that rs180940944 (NBEA) is associated with an increased NMIBC tumour size at the time of diagnosis. Given study limitations, further replication is essential to validate the finding. PATIENT SUMMARY: The current study reports on a genome-wide association study on non-muscle-invasive bladder cancer tumour and patient characteristics. We suggest that NBEA gene might be associated with increased tumour size at th

Published
2019

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