92 results on '"Tomczyk K."'
Search Results
2. Clinical models are inaccurate in predicting bile duct stones in situ for patients with gallbladder
- Author
-
Topal, B., Fieuws, S., Tomczyk, K., Aerts, R., Van Steenbergen, W., Verslype, C., and Penninckx, F.
- Abstract
Abstract: Background: The probability that a patient has common bile duct stones (CBDS) is a key factor in determining diagnostic and treatment strategies. This prospective cohort study evaluated the accuracy of clinical models in predicting CBDS for patients who will undergo cholecystectomy for lithiasis. Methods: From October 2005 until September 2006, 335 consecutive patients with symptoms of gallstone disease underwent cholecystectomy. Statistical analysis was performed on prospective patient data obtained at the time of first presentation to the hospital. Demonstrable CBDS at the time of endoscopic retrograde cholangiopancreatography (ERCP) or intraoperative cholangiography (IOC) was considered the gold standard for the presence of CBDS. Results: Common bile duct stones were demonstrated in 53 patients. For 35 patients, ERCP was performed, with successful stone clearance in 24 of 30 patients who had proven CBDS. In 29 patients, IOC showed CBDS, which were managed successfully via laparoscopic common bile duct exploration, with stone extraction at the time of cholecystectomy. Prospective validation of the existing model for CBDS resulted in a predictive accuracy rate of 73%. The new model showed a predictive accuracy rate of 79%. Conclusion: Clinical models are inaccurate in predicting CBDS in patients with cholelithiasis. Management strategies should be based on the local availability of therapeutic expertise.
- Published
- 2024
- Full Text
- View/download PDF
3. Laparoscopical Repair
- Author
-
Berger, D., Bientzle, M., Miserez, M., Tomczyk, K., Penninckx, F., Elieson, M. J., Whitaker, J. M., LeBlanc, K. A., Kukleta, Jan F., Ramshaw, B., Schumpelick, Volker, editor, and Fitzgibbons, Robert J., editor
- Published
- 2007
- Full Text
- View/download PDF
4. Aliphatic-aromatic poly(ester-carbonate)s obtained from simple carbonate esters, α,ω-aliphatic diols and dimethyl terephthalate
- Author
-
Mazurek, M., Bruliński, T., Tomczyk, K., Parzuchowski, P., Florjańczyk, Z., Plichta, A., and Rokicki, G.
- Published
- 2015
- Full Text
- View/download PDF
5. Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element
- Author
-
Baxter, J.S., Johnson, N., Tomczyk, K., Gillespie, A., Maguire, S., Brough, R., Fachal, L., Michailidou, K., Bolla, M.K., Wang, Q., Dennis, J., Ahearn, T.U., Andrulis, I.L., Anton-Culver, H., Antonenkova, N.N., Arndt, V., Aronson, K.J., Augustinsson, A., Becher, H., Beckmann, M.W., Behrens, S., Benitez, J., Bermisheva, M., Bogdanova, N.V., Bojesen, S.E., Brenner, H., Brucker, S.Y., Cai, Q.Y., Campa, D., Canzian, F., Castelao, J.E., Chan, T.L., Chang-Claude, J., Chanock, S.J., Chenevix-Trench, G., Choi, J.Y., Clarke, C.L., Collaborators, N., Colonna, S., Conroy, D.M., Couch, F.J., Cox, A., Cross, S.S., Czene, K., Daly, M.B., Devilee, P., Dork, T., Dossus, L., Dwek, M., Eccles, D.M., Ekici, A.B., Eliassen, A.H., Engel, C., Fasching, P.A., Figueroa, J., Flyger, H., Gago-Dominguez, M., Gao, C., Garcia-Closas, M., Garcia-Saenz, J.A., Ghoussaini, M., Giles, G.G., Goldberg, M.S., Gonzalez-Neira, A., Guenel, P., Gundert, M., Haeberle, L., Hahnen, E., Haiman, C.A., Hall, P., Hamann, U., Hartman, M., Hatse, S., Hauke, J., Hollestelle, A., Hoppe, R., Hopper, J.L., Hou, M.F., Ito, H., Iwasaki, M., Jager, A., Jakubowska, A., Janni, W., John, E.M., Joseph, V., Jung, A., Kaaks, R., Kang, D., Keeman, R., Khusnutdinova, E., Kim, S.W., Kosma, V.M., Kraft, P., Kristensen, V.N., Kubelka-Sabit, K., Kurian, A.W., Kwong, A., Lacey, J.V., Lambrechts, D., Larson, N.L., Larsson, S.C., Marchand, L. le, Lejbkowicz, F., Li, J.M., Long, J.R., Lophatananon, A., LubiNski, J., Mannermaa, A., Manoochehri, M., Manoukian, S., Margolin, S., Matsuo, K., Mavroudis, D., Mayes, R., Menon, U., Milne, R.L., Taib, N.A.M., Muir, K., Muranen, T.A., Murphy, R.A., Nevanlinna, H., O'Brien, K.M., Offit, K., Olson, J.E., Olsson, H., Park, S.K., Park-Simon, T.W., Patel, A.V., Peterlongo, P., Peto, J., Plaseska-Karanfilska, D., Presneau, N., Pylkas, K., Rack, B., Rennert, G., Romero, A., Ruebner, M., Rudiger, T., Saloustros, E., Sandler, D.P., Sawyer, E.J., Schmidt, M.K., Schmutzler, R.K., Schneeweiss, A., Schoemaker, M.J., Shah, M., Shen, C.Y., Shu, X.O., Simard, J., Southey, M.C., Stone, J., Surowy, H., Swerdlow, A.J., Tamimi, R.M., Tapper, W.J., Taylor, J.A., Teo, S.H., Teras, L.R., Terry, M.B., Toland, A.E., Tomlinson, I., Truong, T., Tseng, C.C., Untch, M., Vachon, C.M., Ouweland, A.M.W. van den, Wang, S.S., Weinberg, C.R., Wendt, C., Winham, S.J., Winqvist, R., Wolk, A., Wu, A.H., Yamaji, T., Zheng, W., Ziogas, A., Pharoah, P.D.P., Dunning, A.M., Easton, D.F., Pettitt, S.J., Lord, C.J., Haider, S., Orr, N., Fletcher, O., kConFab Investigators, ABCTB Investigators, Medical Oncology, Clinical Genetics, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, Biosciences, Dennis, Joe [0000-0003-4591-1214], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository
- Subjects
Basic medicine ,breast cancer risk ,0302 clinical medicine ,Transcription (biology) ,Risk Factors ,WIDE ASSOCIATION ,TRANSCRIPTION ,Promoter Regions, Genetic ,Genetics (clinical) ,Sequence Deletion ,Genetics ,Genetics & Heredity ,0303 health sciences ,Chromosome Mapping ,3. Good health ,030220 oncology & carcinogenesis ,Chromosomes, Human, Pair 2 ,Pair 2 ,Female ,Medical Genetics ,Life Sciences & Biomedicine ,Human ,Tumor suppressor gene ,SUSCEPTIBILITY LOCI ,In silico ,3122 Cancers ,Locus (genetics) ,Breast Neoplasms ,Biology ,Chromosomes ,Article ,Cell Line ,RNAS ,Promoter Regions ,03 medical and health sciences ,functional annotation ,risk locus ,CRISPR-Cas Systems ,Genetic Association Studies ,Genetic Variation ,Humans ,Insulin-Like Growth Factor Binding Protein 5 ,Molecular Sequence Annotation ,11Q13 ,Genetic ,SDG 3 - Good Health and Well-being ,Enhancer ,Transcription factor ,030304 developmental biology ,Medicinsk genetik ,Reporter gene ,Science & Technology ,IDENTIFICATION ,Clinical medicine ,Estrogen receptor alpha - Abstract
A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10-31). ispartof: AMERICAN JOURNAL OF HUMAN GENETICS vol:108 issue:7 pages:1190-1203 ispartof: location:United States status: published
- Published
- 2021
6. CYP3A7*1C allele:linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers
- Author
-
Johnson, N. (Nichola), Maguire, S. (Sarah), Morra, A. (Anna), Kapoor, P. M. (Pooja Middha), Tomczyk, K. (Katarzyna), Jones, M. E. (Michael E.), Schoemaker, M. J. (Minouk J.), Gilham, C. (Clare), Bolla, M. K. (Manjeet K.), Wang, Q. (Qin), Dennis, J. (Joe), Ahearn, T. U. (Thomas U.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antonenkova, N. N. (Natalia N.), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Augustinsson, A. (Annelie), Baynes, C. (Caroline), Freeman, L. E. (Laura E. Beane), Beckmann, M. W. (Matthias W.), Benitez, J. (Javier), Bermisheva, M. (Marina), Blomqvist, C. (Carl), Boeckx, B. (Bram), Bogdanova, N. V. (Natalia V.), Bojesen, S. E. (Stig E.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Burwinkel, B. (Barbara), Campa, D. (Daniele), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chanock, S. J. (Stephen J.), Chenevix-Trench, G. (Georgia), Clarke, C. L. (Christine L.), Conroy, D. M. (Don M.), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Doerk, T. (Thilo), Eliassen, A. H. (A. Heather), Engel, C. (Christoph), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Floris, G. (Giuseppe), Flyger, H. (Henrik), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garcia-Closas, M. (Montserrat), Gaudet, M. M. (Mia M.), Giles, G. G. (Graham G.), Goldberg, M. S. (Mark S.), Gonzalez-Neira, A. (Anna), Guenel, P. (Pascal), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Harrington, P. A. (Patricia A.), Hart, S. N. (Steven N.), Hooning, M. J. (Maartje J.), Hopper, J. L. (John L.), Howell, A. (Anthony), Hunter, D. J. (David J.), Jager, A. (Agnes), Jakubowska, A. (Anna), John, E. M. (Esther M.), Kaaks, R. (Rudolf), Keeman, R. (Renske), Khusnutdinova, E. (Elza), Kitahara, C. M. (Cari M.), Kosma, V.-M. (Veli-Matti), Koutros, S. (Stella), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kurian, A. W. (Allison W.), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Linet, M. (Martha), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J. W. (John W. M.), Mavroudis, D. (Dimitrios), Mayes, R. (Rebecca), Meindl, A. (Alfons), Milne, R. L. (Roger L.), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Newman, W. G. (William G.), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Obi, N. (Nadia), Olshan, A. F. (Andrew F.), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Orban, E. (Ester), Park-Simon, T.-W. (Tjoung-Won), Peterlongo, P. (Paolo), Plaseska-Karanfilska, D. (Dijana), Pylkäs, K. (Katri), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Ruddy, K. J. (Kathryn J.), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmutzler, R. K. (Rita K.), Scott, C. (Christopher), Shu, X.-O. (Xiao-Ou), Simard, J. (Jacques), Smichkoska, S. (Snezhana), Sohn, C. (Christof), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Stone, J. (Jennifer), Tamimi, R. M. (Rulla M.), Taylor, J. A. (Jack A.), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Truong, T. (Therese), Vachon, C. M. (Celine M.), van Veen, E. M. (Elke M.), Wang, S. S. (Sophia S.), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Wildiers, H. (Hans), Winqvist, R. (Robert), Wolk, A. (Alicja), Zheng, W. (Wei), Ziogas, A. (Argyrios), Dunning, A. M. (Alison M.), Pharoah, P. D. (Paul D. P.), Easton, D. F. (Douglas F.), Howie, A. F. (A. Forbes), Peto, J. (Julian), dos-Santos-Silva, I. (Isabel), Swerdlow, A. J. (Anthony J.), Chang-Claude, J. (Jenny), Schmidt, M. K. (Marjanka K.), Orr, N. (Nick), and Fletcher, O. (Olivia)
- Abstract
Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (−49.2%, 95% CI −56.1% to −41.1%, P = 3.1 × 10⁻¹⁸); in follow-up analyses, rs45446698-C was also associated with lower progesterone (−26.7%, 95% CI −39.4% to −11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82–0.91, P = 6.9 × 10⁻¹⁸). Conclusions: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.
- Published
- 2021
7. Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element.
- Author
-
Baxter J.S., Johnson N., Tomczyk K., Gillespie A., Maguire S., Brough R., Fachal L., Michailidou K., Bolla M.K., Wang Q., Dennis J., Ahearn T.U., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arndt V., Aronson K.J., Augustinsson A., Becher H., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bogdanova N.V., Bojesen S.E., Brenner H., Brucker S.Y., Cai Q., Campa D., Canzian F., Castelao J.E., Chan T.L., Chang-Claude J., Chanock S.J., Chenevix-Trench G., Choi J.-Y., Clarke C.L., Colonna S., Conroy D.M., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Devilee P., Dork T., Dossus L., Dwek M., Eccles D.M., Ekici A.B., Eliassen A.H., Engel C., Fasching P.A., Figueroa J., Flyger H., Gago-Dominguez M., Gao C., Garcia-Closas M., Garcia-Saenz J.A., Ghoussaini M., Giles G.G., Goldberg M.S., Gonzalez-Neira A., Guenel P., Gundert M., Haeberle L., Hahnen E., Haiman C.A., Hall P., Hamann U., Hartman M., Hatse S., Hauke J., Hollestelle A., Hoppe R., Hopper J.L., Hou M.-F., Ito H., Iwasaki M., Jager A., Jakubowska A., Janni W., John E.M., Joseph V., Jung A., Kaaks R., Kang D., Keeman R., Khusnutdinova E., Kim S.-W., Kosma V.-M., Kraft P., Kristensen V.N., Kubelka-Sabit K., Kurian A.W., Kwong A., Lacey J.V., Lambrechts D., Larson N.L., Larsson S.C., Le Marchand L., Lejbkowicz F., Li J., Long J., Lophatananon A., Lubinski J., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Matsuo K., Mavroudis D., Mayes R., Menon U., Milne R.L., Mohd Taib N.A., Muir K., Muranen T.A., Murphy R.A., Nevanlinna H., O'Brien K.M., Offit K., Olson J.E., Olsson H., Park S.K., Park-Simon T.-W., Patel A.V., Peterlongo P., Peto J., Plaseska-Karanfilska D., Presneau N., Pylkas K., Rack B., Rennert G., Romero A., Ruebner M., Rudiger T., Saloustros E., Sandler D.P., Sawyer E.J., Schmidt M.K., Schmutzler R.K., Schneeweiss A., Schoemaker M.J., Shah M., Shen C.-Y., Shu X.-O., Simard J., Southey M.C., Stone J., Surowy H., Swerdlow A.J., Tamimi R.M., Tapper W.J., Taylor J.A., Teo S.H., Teras L.R., Terry M.B., Toland A.E., Tomlinson I., Truong T., Tseng C.-C., Untch M., Vachon C.M., van den Ouweland A.M.W., Wang S.S., Weinberg C.R., Wendt C., Winham S.J., Winqvist R., Wolk A., Wu A.H., Yamaji T., Zheng W., Ziogas A., Pharoah P.D.P., Dunning A.M., Easton D.F., Pettitt S.J., Lord C.J., Haider S., Orr N., Fletcher O., Baxter J.S., Johnson N., Tomczyk K., Gillespie A., Maguire S., Brough R., Fachal L., Michailidou K., Bolla M.K., Wang Q., Dennis J., Ahearn T.U., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arndt V., Aronson K.J., Augustinsson A., Becher H., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bogdanova N.V., Bojesen S.E., Brenner H., Brucker S.Y., Cai Q., Campa D., Canzian F., Castelao J.E., Chan T.L., Chang-Claude J., Chanock S.J., Chenevix-Trench G., Choi J.-Y., Clarke C.L., Colonna S., Conroy D.M., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Devilee P., Dork T., Dossus L., Dwek M., Eccles D.M., Ekici A.B., Eliassen A.H., Engel C., Fasching P.A., Figueroa J., Flyger H., Gago-Dominguez M., Gao C., Garcia-Closas M., Garcia-Saenz J.A., Ghoussaini M., Giles G.G., Goldberg M.S., Gonzalez-Neira A., Guenel P., Gundert M., Haeberle L., Hahnen E., Haiman C.A., Hall P., Hamann U., Hartman M., Hatse S., Hauke J., Hollestelle A., Hoppe R., Hopper J.L., Hou M.-F., Ito H., Iwasaki M., Jager A., Jakubowska A., Janni W., John E.M., Joseph V., Jung A., Kaaks R., Kang D., Keeman R., Khusnutdinova E., Kim S.-W., Kosma V.-M., Kraft P., Kristensen V.N., Kubelka-Sabit K., Kurian A.W., Kwong A., Lacey J.V., Lambrechts D., Larson N.L., Larsson S.C., Le Marchand L., Lejbkowicz F., Li J., Long J., Lophatananon A., Lubinski J., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Matsuo K., Mavroudis D., Mayes R., Menon U., Milne R.L., Mohd Taib N.A., Muir K., Muranen T.A., Murphy R.A., Nevanlinna H., O'Brien K.M., Offit K., Olson J.E., Olsson H., Park S.K., Park-Simon T.-W., Patel A.V., Peterlongo P., Peto J., Plaseska-Karanfilska D., Presneau N., Pylkas K., Rack B., Rennert G., Romero A., Ruebner M., Rudiger T., Saloustros E., Sandler D.P., Sawyer E.J., Schmidt M.K., Schmutzler R.K., Schneeweiss A., Schoemaker M.J., Shah M., Shen C.-Y., Shu X.-O., Simard J., Southey M.C., Stone J., Surowy H., Swerdlow A.J., Tamimi R.M., Tapper W.J., Taylor J.A., Teo S.H., Teras L.R., Terry M.B., Toland A.E., Tomlinson I., Truong T., Tseng C.-C., Untch M., Vachon C.M., van den Ouweland A.M.W., Wang S.S., Weinberg C.R., Wendt C., Winham S.J., Winqvist R., Wolk A., Wu A.H., Yamaji T., Zheng W., Ziogas A., Pharoah P.D.P., Dunning A.M., Easton D.F., Pettitt S.J., Lord C.J., Haider S., Orr N., and Fletcher O.
- Abstract
A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 x 10-31).Copyright © 2021 The Authors
- Published
- 2021
8. CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers.
- Author
-
Johnson N., Maguire S., Morra A., Kapoor P.M., Tomczyk K., Jones M.E., Schoemaker M.J., Gilham C., Bolla M.K., Wang Q., Dennis J., Ahearn T.U., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arndt V., Aronson K.J., Augustinsson A., Baynes C., Freeman L.E.B., Beckmann M.W., Benitez J., Bermisheva M., Blomqvist C., Boeckx B., Bogdanova N.V., Bojesen S.E., Brauch H., Brenner H., Burwinkel B., Campa D., Canzian F., Castelao J.E., Chanock S.J., Chenevix-Trench G., Clarke C.L., Borresen-Dale A.-L., Alnaes G.I.G., Sahlberg K.K., Ottestad L., Karesen R., Schlichting E., Holmen M.M., Sauer T., Haakensen V., Engebraten O., Naume B., Fossa A., Kiserud C.E., Reinertsen K.V., Helland A., Riis M., Geisler J., Conroy D.M., Couch F.J., Cox A., Cross S.S., Czene K., Dork T., Eliassen A.H., Engel C., Evans D.G., Fasching P.A., Figueroa J., Floris G., Flyger H., Gago-Dominguez M., Gapstur S.M., Garcia-Closas M., Gaudet M.M., Giles G.G., Goldberg M.S., Gonzalez-Neira A., Bowtell D.D.L., Webb P.M., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., Hooning M.J., Hopper J.L., Howell A., Hunter D.J., Clarke C., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Amor D., Andrews L., Antill Y., Balleine R., Beesley J., Bennett I., Bogwitz M., Botes L., Brennan M., Brown M., Buckley M., Burke J., Butow P., Caldon L., Campbell I., Chauhan D., Chauhan M., Christian A., Cohen P., Colley A., Crook A., Cui J., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dickson R., Dixon J., Edkins T., Edwards S., Farshid G., Fellows A., Fenton G., Field M., Flanagan J., Fong P., Forrest L., Fox S., French J., Friedlander M., Gaff C., Gattas M., George P., Greening S., Harris M., Hart S., Hayward N., Hopper J., Hoskins C., Hunt C., James P., Jenkins M., Kidd A., Kirk J., Koehler J., Kollias J., Lakhani S., Lawrence M., Lindeman G., Lipton L., Lobb L., Mann G., Marsh D., McLachlan S.A., Meiser B., Milne R.L., Nightingale S., O'Connell S., O'Sullivan S., Ortega D.G., Pachter N., Patterson B., Pearn A., Phillips K., Pieper E., Rickard E., Robinson B., Saleh M., Salisbury E., Saunders C., Saunus J., Sexton A., Shelling A., Simpson P., Southey M.C., Spurdle A., Taylor J., Taylor R., Thorne H., Trainer A., Tucker K., Visvader J., Walker L., Williams R., Winship I., Young M.A., Jager A., Jakubowska A., John E.M., Keeman R., Khusnutdinova E., Kitahara C.M., Kosma V.-M., Koutros S., Kraft P., Kristensen V.N., Kurian A.W., Lambrechts D., Le Marchand L., Linet M., Lubinski J., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mavroudis D., Mayes R., Meindl A., Neuhausen S.L., Nevanlinna H., Newman W.G., Nielsen S.F., Nordestgaard B.G., Obi N., Olshan A.F., Olson J.E., Olsson H., Orban E., Park-Simon T.-W., Peterlongo P., Plaseska-Karanfilska D., Pylkas K., Rennert G., Rennert H.S., Ruddy K.J., Saloustros E., Sandler D.P., Sawyer E.J., Schmutzler R.K., Scott C., Shu X.-O., Simard J., Smichkoska S., Sohn C., Spinelli J.J., Stone J., Tamimi R.M., Taylor J.A., Tollenaar R.A.E.M., Tomlinson I., Troester M.A., Truong T., Vachon C.M., van Veen E.M., Wang S.S., Weinberg C.R., Wendt C., Wildiers H., Winqvist R., Wolk A., Zheng W., Ziogas A., Dunning A.M., Pharoah P.D.P., Easton D.F., Howie A.F., Peto J., dos-Santos-Silva I., Swerdlow A.J., Chang-Claude J., Schmidt M.K., Orr N., Fletcher O., Johnson N., Maguire S., Morra A., Kapoor P.M., Tomczyk K., Jones M.E., Schoemaker M.J., Gilham C., Bolla M.K., Wang Q., Dennis J., Ahearn T.U., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arndt V., Aronson K.J., Augustinsson A., Baynes C., Freeman L.E.B., Beckmann M.W., Benitez J., Bermisheva M., Blomqvist C., Boeckx B., Bogdanova N.V., Bojesen S.E., Brauch H., Brenner H., Burwinkel B., Campa D., Canzian F., Castelao J.E., Chanock S.J., Chenevix-Trench G., Clarke C.L., Borresen-Dale A.-L., Alnaes G.I.G., Sahlberg K.K., Ottestad L., Karesen R., Schlichting E., Holmen M.M., Sauer T., Haakensen V., Engebraten O., Naume B., Fossa A., Kiserud C.E., Reinertsen K.V., Helland A., Riis M., Geisler J., Conroy D.M., Couch F.J., Cox A., Cross S.S., Czene K., Dork T., Eliassen A.H., Engel C., Evans D.G., Fasching P.A., Figueroa J., Floris G., Flyger H., Gago-Dominguez M., Gapstur S.M., Garcia-Closas M., Gaudet M.M., Giles G.G., Goldberg M.S., Gonzalez-Neira A., Bowtell D.D.L., Webb P.M., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., Hooning M.J., Hopper J.L., Howell A., Hunter D.J., Clarke C., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Amor D., Andrews L., Antill Y., Balleine R., Beesley J., Bennett I., Bogwitz M., Botes L., Brennan M., Brown M., Buckley M., Burke J., Butow P., Caldon L., Campbell I., Chauhan D., Chauhan M., Christian A., Cohen P., Colley A., Crook A., Cui J., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dickson R., Dixon J., Edkins T., Edwards S., Farshid G., Fellows A., Fenton G., Field M., Flanagan J., Fong P., Forrest L., Fox S., French J., Friedlander M., Gaff C., Gattas M., George P., Greening S., Harris M., Hart S., Hayward N., Hopper J., Hoskins C., Hunt C., James P., Jenkins M., Kidd A., Kirk J., Koehler J., Kollias J., Lakhani S., Lawrence M., Lindeman G., Lipton L., Lobb L., Mann G., Marsh D., McLachlan S.A., Meiser B., Milne R.L., Nightingale S., O'Connell S., O'Sullivan S., Ortega D.G., Pachter N., Patterson B., Pearn A., Phillips K., Pieper E., Rickard E., Robinson B., Saleh M., Salisbury E., Saunders C., Saunus J., Sexton A., Shelling A., Simpson P., Southey M.C., Spurdle A., Taylor J., Taylor R., Thorne H., Trainer A., Tucker K., Visvader J., Walker L., Williams R., Winship I., Young M.A., Jager A., Jakubowska A., John E.M., Keeman R., Khusnutdinova E., Kitahara C.M., Kosma V.-M., Koutros S., Kraft P., Kristensen V.N., Kurian A.W., Lambrechts D., Le Marchand L., Linet M., Lubinski J., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mavroudis D., Mayes R., Meindl A., Neuhausen S.L., Nevanlinna H., Newman W.G., Nielsen S.F., Nordestgaard B.G., Obi N., Olshan A.F., Olson J.E., Olsson H., Orban E., Park-Simon T.-W., Peterlongo P., Plaseska-Karanfilska D., Pylkas K., Rennert G., Rennert H.S., Ruddy K.J., Saloustros E., Sandler D.P., Sawyer E.J., Schmutzler R.K., Scott C., Shu X.-O., Simard J., Smichkoska S., Sohn C., Spinelli J.J., Stone J., Tamimi R.M., Taylor J.A., Tollenaar R.A.E.M., Tomlinson I., Troester M.A., Truong T., Vachon C.M., van Veen E.M., Wang S.S., Weinberg C.R., Wendt C., Wildiers H., Winqvist R., Wolk A., Zheng W., Ziogas A., Dunning A.M., Pharoah P.D.P., Easton D.F., Howie A.F., Peto J., dos-Santos-Silva I., Swerdlow A.J., Chang-Claude J., Schmidt M.K., Orr N., and Fletcher O.
- Abstract
Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Method(s): We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Result(s): For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 x 10-18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 x 10-8). Conclusion(s): The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.Copyright © 2021, The Author(s).
- Published
- 2021
9. CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers
- Author
-
Johnson, N, Maguire, S, Morra, A, Kapoor, PM, Tomczyk, K, Jones, ME, Schoemaker, MJ, Gilham, C, Bolla, MK, Wang, Q, Dennis, J, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Augustinsson, A, Baynes, C, Freeman, LEB, Beckmann, MW, Benitez, J, Bermisheva, M, Blomqvist, C, Boeckx, B, Bogdanova, NV, Bojesen, SE, Brauch, H, Brenner, H, Burwinkel, B, Campa, D, Canzian, F, Castelao, JE, Chanock, SJ, Chenevix-Trench, G, Clarke, CL, Conroy, DM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Doerk, T, Eliassen, AH, Engel, C, Evans, DG, Fasching, PA, Figueroa, J, Floris, G, Flyger, H, Gago-Dominguez, M, Gapstur, SM, Garcia-Closas, M, Gaudet, MM, Giles, GG, Goldberg, MS, Gonzalez-Neira, A, Guenel, P, Hahnen, E, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Harrington, PA, Hart, SN, Hooning, MJ, Hopper, JL, Howell, A, Hunter, DJ, Jager, A, Jakubowska, A, John, EM, Kaaks, R, Keeman, R, Khusnutdinova, E, Kitahara, CM, Kosma, V-M, Koutros, S, Kraft, P, Kristensen, VN, Kurian, AW, Lambrechts, D, Le Marchand, L, Linet, M, Lubinski, J, Mannermaa, A, Manoukian, S, Margolin, S, Martens, JWM, Mavroudis, D, Mayes, R, Meindl, A, Milne, RL, Neuhausen, SL, Nevanlinna, H, Newman, WG, Nielsen, SF, Nordestgaard, BG, Obi, N, Olshan, AF, Olson, JE, Olsson, H, Orban, E, Park-Simon, T-W, Peterlongo, P, Plaseska-Karanfilska, D, Pylkas, K, Rennert, G, Rennert, HS, Ruddy, KJ, Saloustros, E, Sandler, DP, Sawyer, EJ, Schmutzler, RK, Scott, C, Shu, X-O, Simard, J, Smichkoska, S, Sohn, C, Southey, MC, Spinelli, JJ, Stone, J, Tamimi, RM, Taylor, JA, Tollenaar, RAEM, Tomlinson, I, Troester, MA, Truong, T, Vachon, CM, van Veen, EM, Wang, SS, Weinberg, CR, Wendt, C, Wildiers, H, Winqvist, R, Wolk, A, Zheng, W, Ziogas, A, Dunning, AM, Pharoah, PDP, Easton, DF, Howie, AF, Peto, J, dos-Santos-Silva, I, Swerdlow, AJ, Chang-Claude, J, Schmidt, MK, Orr, N, Fletcher, O, Johnson, N, Maguire, S, Morra, A, Kapoor, PM, Tomczyk, K, Jones, ME, Schoemaker, MJ, Gilham, C, Bolla, MK, Wang, Q, Dennis, J, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Augustinsson, A, Baynes, C, Freeman, LEB, Beckmann, MW, Benitez, J, Bermisheva, M, Blomqvist, C, Boeckx, B, Bogdanova, NV, Bojesen, SE, Brauch, H, Brenner, H, Burwinkel, B, Campa, D, Canzian, F, Castelao, JE, Chanock, SJ, Chenevix-Trench, G, Clarke, CL, Conroy, DM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Doerk, T, Eliassen, AH, Engel, C, Evans, DG, Fasching, PA, Figueroa, J, Floris, G, Flyger, H, Gago-Dominguez, M, Gapstur, SM, Garcia-Closas, M, Gaudet, MM, Giles, GG, Goldberg, MS, Gonzalez-Neira, A, Guenel, P, Hahnen, E, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Harrington, PA, Hart, SN, Hooning, MJ, Hopper, JL, Howell, A, Hunter, DJ, Jager, A, Jakubowska, A, John, EM, Kaaks, R, Keeman, R, Khusnutdinova, E, Kitahara, CM, Kosma, V-M, Koutros, S, Kraft, P, Kristensen, VN, Kurian, AW, Lambrechts, D, Le Marchand, L, Linet, M, Lubinski, J, Mannermaa, A, Manoukian, S, Margolin, S, Martens, JWM, Mavroudis, D, Mayes, R, Meindl, A, Milne, RL, Neuhausen, SL, Nevanlinna, H, Newman, WG, Nielsen, SF, Nordestgaard, BG, Obi, N, Olshan, AF, Olson, JE, Olsson, H, Orban, E, Park-Simon, T-W, Peterlongo, P, Plaseska-Karanfilska, D, Pylkas, K, Rennert, G, Rennert, HS, Ruddy, KJ, Saloustros, E, Sandler, DP, Sawyer, EJ, Schmutzler, RK, Scott, C, Shu, X-O, Simard, J, Smichkoska, S, Sohn, C, Southey, MC, Spinelli, JJ, Stone, J, Tamimi, RM, Taylor, JA, Tollenaar, RAEM, Tomlinson, I, Troester, MA, Truong, T, Vachon, CM, van Veen, EM, Wang, SS, Weinberg, CR, Wendt, C, Wildiers, H, Winqvist, R, Wolk, A, Zheng, W, Ziogas, A, Dunning, AM, Pharoah, PDP, Easton, DF, Howie, AF, Peto, J, dos-Santos-Silva, I, Swerdlow, AJ, Chang-Claude, J, Schmidt, MK, Orr, N, and Fletcher, O
- Abstract
BACKGROUND: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. METHODS: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. RESULTS: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 × 10-18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 × 10-8). CONCLUSIONS: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.
- Published
- 2021
10. Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element
- Author
-
Baxter, JS, Johnson, N, Tomczyk, K, Gillespie, A, Maguire, S, Brough, R, Fachal, L, Michailidou, K, Bolla, MK, Wang, Q, Dennis, J, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Augustinsson, A, Becher, H, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bogdanova, N, Bojesen, SE, Brenner, H, Brucker, SY, Cai, Q, Campa, D, Canzian, F, Castelao, JE, Chan, TL, Chang-Claude, J, Chanock, SJ, Chenevix-Trench, G, Choi, J-Y, Clarke, CL, Collaborators, N, Colonna, S, Conroy, DM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Doerk, T, Dossus, L, Dwek, M, Eccles, DM, Ekici, AB, Eliassen, AH, Engel, C, Fasching, PA, Figueroa, J, Flyger, H, Gago-Dominguez, M, Gao, C, Garcia-Closas, M, Garcia-Saenz, JA, Ghoussaini, M, Giles, GG, Goldberg, MS, Gonzalez-Neira, A, Guenel, P, Guendert, M, Haeberle, L, Hahnen, E, Haiman, CA, Hall, P, Hamann, U, Hartman, M, Hatse, S, Hauke, J, Hollestelle, A, Hoppe, R, Hopper, JL, Hou, M-F, Ito, H, Iwasaki, M, Jager, A, Jakubowska, A, Janni, W, John, EM, Joseph, V, Jung, A, Kaaks, R, Kang, D, Keeman, R, Khusnutdinova, E, Kim, S-W, Kosma, V-M, Kraft, P, Kristensen, VN, Kubelka-Sabit, K, Kurian, AW, Kwong, A, Lacey, J, Lambrechts, D, Larson, NL, Larsson, SC, Le Marchand, L, Lejbkowicz, F, Li, J, Long, J, Lophatananon, A, LubiNski, J, Mannermaa, A, Manoochehri, M, Manoukian, S, Margolin, S, Matsuo, K, Mavroudis, D, Mayes, R, Menon, U, Milne, RL, Taib, NAM, Muir, K, Muranen, TA, Murphy, RA, Nevanlinna, H, O'Brien, KM, Offit, K, Olson, JE, Olsson, H, Park, SK, Park-Simon, T-W, Patel, A, Peterlongo, P, Peto, J, Plaseska-Karanfilska, D, Presneau, N, Pylkas, K, Rack, B, Rennert, G, Romero, A, Ruebner, M, Ruediger, T, Saloustros, E, Sandler, DP, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Schneeweiss, A, Schoemaker, MJ, Shah, M, Shen, C-Y, Shu, X-O, Simard, J, Southey, MC, Stone, J, Surowy, H, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Taylor, JA, Teo, SH, Teras, LR, Terry, MB, Toland, AE, Tomlinson, I, Truong, T, Tseng, C-C, Untch, M, Vachon, CM, van den Ouweland, AMW, Wang, SS, Weinberg, CR, Wendt, C, Winham, SJ, Winqvist, R, Wolk, A, Wu, AH, Yamaji, T, Zheng, W, Ziogas, A, Pharoah, PDP, Dunning, AM, Easton, DF, Pettitt, SJ, Lord, CJ, Haider, S, Orr, N, Fletcher, O, Baxter, JS, Johnson, N, Tomczyk, K, Gillespie, A, Maguire, S, Brough, R, Fachal, L, Michailidou, K, Bolla, MK, Wang, Q, Dennis, J, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Augustinsson, A, Becher, H, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bogdanova, N, Bojesen, SE, Brenner, H, Brucker, SY, Cai, Q, Campa, D, Canzian, F, Castelao, JE, Chan, TL, Chang-Claude, J, Chanock, SJ, Chenevix-Trench, G, Choi, J-Y, Clarke, CL, Collaborators, N, Colonna, S, Conroy, DM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Doerk, T, Dossus, L, Dwek, M, Eccles, DM, Ekici, AB, Eliassen, AH, Engel, C, Fasching, PA, Figueroa, J, Flyger, H, Gago-Dominguez, M, Gao, C, Garcia-Closas, M, Garcia-Saenz, JA, Ghoussaini, M, Giles, GG, Goldberg, MS, Gonzalez-Neira, A, Guenel, P, Guendert, M, Haeberle, L, Hahnen, E, Haiman, CA, Hall, P, Hamann, U, Hartman, M, Hatse, S, Hauke, J, Hollestelle, A, Hoppe, R, Hopper, JL, Hou, M-F, Ito, H, Iwasaki, M, Jager, A, Jakubowska, A, Janni, W, John, EM, Joseph, V, Jung, A, Kaaks, R, Kang, D, Keeman, R, Khusnutdinova, E, Kim, S-W, Kosma, V-M, Kraft, P, Kristensen, VN, Kubelka-Sabit, K, Kurian, AW, Kwong, A, Lacey, J, Lambrechts, D, Larson, NL, Larsson, SC, Le Marchand, L, Lejbkowicz, F, Li, J, Long, J, Lophatananon, A, LubiNski, J, Mannermaa, A, Manoochehri, M, Manoukian, S, Margolin, S, Matsuo, K, Mavroudis, D, Mayes, R, Menon, U, Milne, RL, Taib, NAM, Muir, K, Muranen, TA, Murphy, RA, Nevanlinna, H, O'Brien, KM, Offit, K, Olson, JE, Olsson, H, Park, SK, Park-Simon, T-W, Patel, A, Peterlongo, P, Peto, J, Plaseska-Karanfilska, D, Presneau, N, Pylkas, K, Rack, B, Rennert, G, Romero, A, Ruebner, M, Ruediger, T, Saloustros, E, Sandler, DP, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Schneeweiss, A, Schoemaker, MJ, Shah, M, Shen, C-Y, Shu, X-O, Simard, J, Southey, MC, Stone, J, Surowy, H, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Taylor, JA, Teo, SH, Teras, LR, Terry, MB, Toland, AE, Tomlinson, I, Truong, T, Tseng, C-C, Untch, M, Vachon, CM, van den Ouweland, AMW, Wang, SS, Weinberg, CR, Wendt, C, Winham, SJ, Winqvist, R, Wolk, A, Wu, AH, Yamaji, T, Zheng, W, Ziogas, A, Pharoah, PDP, Dunning, AM, Easton, DF, Pettitt, SJ, Lord, CJ, Haider, S, Orr, N, and Fletcher, O
- Abstract
A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10-31).
- Published
- 2021
11. Common Susceptibility Loci for Male Breast Cancer
- Author
-
Maguire, S, Perraki, E, Tomczyk, K, Jones, ME, Fletcher, O, Pugh, M, Winter, T, Thompson, K, Cooke, R, Trainer, A, James, P, Bojesen, S, Flyger, H, Nevanlinna, H, Mattson, J, Friedman, E, Laitman, Y, Palli, D, Masala, G, Zanna, I, Ottini, L, Silvestri, V, Hollestelle, A, Hooning, MJ, Novakovic, S, Krajc, M, Gago-Dominguez, M, Esteban Castelao, J, Olsson, H, Hedenfalk, I, Saloustros, E, Georgoulias, V, Easton, DF, Pharoah, P, Dunning, AM, Bishop, DT, Neuhausen, SL, Steele, L, Ashworth, A, Closas, MG, Houlston, R, Swerdlow, A, Orr, N, Maguire, S, Perraki, E, Tomczyk, K, Jones, ME, Fletcher, O, Pugh, M, Winter, T, Thompson, K, Cooke, R, Trainer, A, James, P, Bojesen, S, Flyger, H, Nevanlinna, H, Mattson, J, Friedman, E, Laitman, Y, Palli, D, Masala, G, Zanna, I, Ottini, L, Silvestri, V, Hollestelle, A, Hooning, MJ, Novakovic, S, Krajc, M, Gago-Dominguez, M, Esteban Castelao, J, Olsson, H, Hedenfalk, I, Saloustros, E, Georgoulias, V, Easton, DF, Pharoah, P, Dunning, AM, Bishop, DT, Neuhausen, SL, Steele, L, Ashworth, A, Closas, MG, Houlston, R, Swerdlow, A, and Orr, N
- Abstract
BACKGROUND: The etiology of male breast cancer (MBC) is poorly understood. In particular, the extent to which the genetic basis of MBC differs from female breast cancer (FBC) is unknown. A previous genome-wide association study of MBC identified 2 predisposition loci for the disease, both of which were also associated with risk of FBC. METHODS: We performed genome-wide single nucleotide polymorphism genotyping of European ancestry MBC case subjects and controls in 3 stages. Associations between directly genotyped and imputed single nucleotide polymorphisms with MBC were assessed using fixed-effects meta-analysis of 1380 cases and 3620 controls. Replication genotyping of 810 cases and 1026 controls was used to validate variants with P values less than 1 × 10-06. Genetic correlation with FBC was evaluated using linkage disequilibrium score regression, by comprehensively examining the associations of published FBC risk loci with risk of MBC and by assessing associations between a FBC polygenic risk score and MBC. All statistical tests were 2-sided. RESULTS: The genome-wide association study identified 3 novel MBC susceptibility loci that attained genome-wide statistical significance (P < 5 × 10-08). Genetic correlation analysis revealed a strong shared genetic basis with estrogen receptor-positive FBC. Men in the top quintile of genetic risk had a fourfold increased risk of breast cancer relative to those in the bottom quintile (odds ratio = 3.86, 95% confidence interval = 3.07 to 4.87, P = 2.08 × 10-30). CONCLUSIONS: These findings advance our understanding of the genetic basis of MBC, providing support for an overlapping genetic etiology with FBC and identifying a fourfold high-risk group of susceptible men.
- Published
- 2021
12. Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element
- Author
-
Baxter, J. S. (Joseph S.), Johnson, N. (Nichola), Tomczyk, K. (Katarzyna), Gillespie, A. (Andrea), Maguire, S. (Sarah), Brough, R. (Rachel), Fachal, L. (Laura), Michailidou, K. (Kyriaki), Bolla, M. K. (Manjeet K.), Wang, Q. (Qin), Dennis, J. (Joe), Ahearn, T. U. (Thomas U.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antonenkova, N. N. (Natalia N.), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Augustinsson, A. (Annelie), Becher, H. (Heiko), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Brenner, H. (Hermann), Brucker, S. Y. (Sara Y.), Cai, Q. (Qiuyin), Campa, D. (Daniele), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chan, T. L. (Tsun L.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Chenevix-Trench, G. (Georgia), Choi, J.-Y. (Ji-Yeob), Clarke, C. L. (Christine L.), Collaborators, N. (Nbcs), Colonna, S. (Sarah), Conroy, D. M. (Don M.), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Devilee, P. (Peter), Doerk, T. (Thilo), Dossus, L. (Laure), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Engel, C. (Christoph), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Flyger, H. (Henrik), Gago-Dominguez, M. (Manuela), Gao, C. (Chi), Garcia-Closas, M. (Montserrat), Garcia-Saenz, J. A. (Jose A.), Ghoussaini, M. (Maya), Giles, G. G. (Graham G.), Goldberg, M. S. (Mark S.), Gonzalez-Neira, A. (Anna), Guenel, P. (Pascal), Guendert, M. (Melanie), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hall, P. (Per), Hamann, U. (Ute), Hartman, M. (Mikael), Hatse, S. (Sigrid), Hauke, J. (Jan), Hollestelle, A. (Antoinette), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Hou, M.-F. (Ming-Feng), Ito, H. (Hidemi), Iwasaki, M. (Motoki), Jager, A. (Agnes), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Joseph, V. (Vijai), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kang, D. (Daehee), Keeman, R. (Renske), Khusnutdinova, E. (Elza), Kim, S.-W. (Sung-Won), Kosma, V.-M. (Veli-Matti), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kubelka-Sabit, K. (Katerina), Kurian, A. W. (Allison W.), Kwong, A. (Ava), Lacey, J. V. (James, V), Lambrechts, D. (Diether), Larson, N. L. (Nicole L.), Larsson, S. C. (Susanna C.), Le Marchand, L. (Loic), Lejbkowicz, F. (Flavio), Li, J. (Jingmei), Long, J. (Jirong), Lophatananon, A. (Artitaya), LubiNski, J. (Jan), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Manoukian, S. (Siranoush), Margolin, S. (Sara), Matsuo, K. (Keitaro), Mavroudis, D. (Dimitrios), Mayes, R. (Rebecca), Menon, U. (Usha), Milne, R. L. (Roger L.), Taib, N. A. (Nur Aishah Mohd), Muir, K. (Kenneth), Muranen, T. A. (Taru A.), Murphy, R. A. (Rachel A.), Nevanlinna, H. (Heli), O'Brien, K. M. (Katie M.), Offit, K. (Kenneth), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Park, S. K. (Sue K.), Park-Simon, T.-W. (Tjoung-Won), Patel, A. V. (Alpa, V), Peterlongo, P. (Paolo), Peto, J. (Julian), Plaseska-Karanfilska, D. (Dijana), Presneau, N. (Nadege), Pylkäs, K. (Katri), Rack, B. (Brigitte), Rennert, G. (Gad), Romero, A. (Atocha), Ruebner, M. (Matthias), Ruediger, T. (Thomas), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, M. K. (Marjanka K.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Schoemaker, M. J. (Minouk J.), Shah, M. (Mitul), Shen, C.-Y. (Chen-Yang), Shu, X.-O. (Xiao-Ou), Simard, J. (Jacques), Southey, M. C. (Melissa C.), Stone, J. (Jennifer), Surowy, H. (Harald), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Taylor, J. A. (Jack A.), Teo, S. H. (Soo Hwang), Teras, L. R. (Lauren R.), Terry, M. B. (Mary Beth), Toland, A. E. (Amanda E.), Tomlinson, I. (Ian), Truong, T. (Therese), Tseng, C.-C. (Chiu-Chen), Untch, M. (Michael), Vachon, C. M. (Celine M.), van den Ouweland, A. M. (Ans M. W.), Wang, S. S. (Sophia S.), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Winham, S. J. (Stacey J.), Winqvist, R. (Robert), Wolk, A. (Alicja), Wu, A. H. (Anna H.), Yamaji, T. (Taiki), Zheng, W. (Wei), Ziogas, A. (Argyrios), Pharoah, P. D. (Paul D. P.), Dunning, A. M. (Alison M.), Easton, D. F. (Douglas F.), Pettitt, S. J. (Stephen J.), Lord, C. J. (Christopher J.), Haider, S. (Syed), Orr, N. (Nick), Fletcher, O. (Olivia), Baxter, J. S. (Joseph S.), Johnson, N. (Nichola), Tomczyk, K. (Katarzyna), Gillespie, A. (Andrea), Maguire, S. (Sarah), Brough, R. (Rachel), Fachal, L. (Laura), Michailidou, K. (Kyriaki), Bolla, M. K. (Manjeet K.), Wang, Q. (Qin), Dennis, J. (Joe), Ahearn, T. U. (Thomas U.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antonenkova, N. N. (Natalia N.), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Augustinsson, A. (Annelie), Becher, H. (Heiko), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Brenner, H. (Hermann), Brucker, S. Y. (Sara Y.), Cai, Q. (Qiuyin), Campa, D. (Daniele), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chan, T. L. (Tsun L.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Chenevix-Trench, G. (Georgia), Choi, J.-Y. (Ji-Yeob), Clarke, C. L. (Christine L.), Collaborators, N. (Nbcs), Colonna, S. (Sarah), Conroy, D. M. (Don M.), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Devilee, P. (Peter), Doerk, T. (Thilo), Dossus, L. (Laure), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Engel, C. (Christoph), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Flyger, H. (Henrik), Gago-Dominguez, M. (Manuela), Gao, C. (Chi), Garcia-Closas, M. (Montserrat), Garcia-Saenz, J. A. (Jose A.), Ghoussaini, M. (Maya), Giles, G. G. (Graham G.), Goldberg, M. S. (Mark S.), Gonzalez-Neira, A. (Anna), Guenel, P. (Pascal), Guendert, M. (Melanie), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hall, P. (Per), Hamann, U. (Ute), Hartman, M. (Mikael), Hatse, S. (Sigrid), Hauke, J. (Jan), Hollestelle, A. (Antoinette), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Hou, M.-F. (Ming-Feng), Ito, H. (Hidemi), Iwasaki, M. (Motoki), Jager, A. (Agnes), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Joseph, V. (Vijai), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kang, D. (Daehee), Keeman, R. (Renske), Khusnutdinova, E. (Elza), Kim, S.-W. (Sung-Won), Kosma, V.-M. (Veli-Matti), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kubelka-Sabit, K. (Katerina), Kurian, A. W. (Allison W.), Kwong, A. (Ava), Lacey, J. V. (James, V), Lambrechts, D. (Diether), Larson, N. L. (Nicole L.), Larsson, S. C. (Susanna C.), Le Marchand, L. (Loic), Lejbkowicz, F. (Flavio), Li, J. (Jingmei), Long, J. (Jirong), Lophatananon, A. (Artitaya), LubiNski, J. (Jan), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Manoukian, S. (Siranoush), Margolin, S. (Sara), Matsuo, K. (Keitaro), Mavroudis, D. (Dimitrios), Mayes, R. (Rebecca), Menon, U. (Usha), Milne, R. L. (Roger L.), Taib, N. A. (Nur Aishah Mohd), Muir, K. (Kenneth), Muranen, T. A. (Taru A.), Murphy, R. A. (Rachel A.), Nevanlinna, H. (Heli), O'Brien, K. M. (Katie M.), Offit, K. (Kenneth), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Park, S. K. (Sue K.), Park-Simon, T.-W. (Tjoung-Won), Patel, A. V. (Alpa, V), Peterlongo, P. (Paolo), Peto, J. (Julian), Plaseska-Karanfilska, D. (Dijana), Presneau, N. (Nadege), Pylkäs, K. (Katri), Rack, B. (Brigitte), Rennert, G. (Gad), Romero, A. (Atocha), Ruebner, M. (Matthias), Ruediger, T. (Thomas), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, M. K. (Marjanka K.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Schoemaker, M. J. (Minouk J.), Shah, M. (Mitul), Shen, C.-Y. (Chen-Yang), Shu, X.-O. (Xiao-Ou), Simard, J. (Jacques), Southey, M. C. (Melissa C.), Stone, J. (Jennifer), Surowy, H. (Harald), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Taylor, J. A. (Jack A.), Teo, S. H. (Soo Hwang), Teras, L. R. (Lauren R.), Terry, M. B. (Mary Beth), Toland, A. E. (Amanda E.), Tomlinson, I. (Ian), Truong, T. (Therese), Tseng, C.-C. (Chiu-Chen), Untch, M. (Michael), Vachon, C. M. (Celine M.), van den Ouweland, A. M. (Ans M. W.), Wang, S. S. (Sophia S.), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Winham, S. J. (Stacey J.), Winqvist, R. (Robert), Wolk, A. (Alicja), Wu, A. H. (Anna H.), Yamaji, T. (Taiki), Zheng, W. (Wei), Ziogas, A. (Argyrios), Pharoah, P. D. (Paul D. P.), Dunning, A. M. (Alison M.), Easton, D. F. (Douglas F.), Pettitt, S. J. (Stephen J.), Lord, C. J. (Christopher J.), Haider, S. (Syed), Orr, N. (Nick), and Fletcher, O. (Olivia)
- Abstract
A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74–0.81, p = 3.1 × 10−31).
- Published
- 2021
13. Clinical models are inaccurate in predicting bile duct stones in situ for patients with gallbladder
- Author
-
Topal, B., Fieuws, S., Tomczyk, K., Aerts, R., Van Steenbergen, W., Verslype, C., and Penninckx, F.
- Published
- 2009
- Full Text
- View/download PDF
14. Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk.
- Author
-
Chajes V., Dugue P.-A., Southey M.C., Giles G.G., English D.R., Milne R.L., Severi G., Ambatipudi S., Cuenin C., Romieu I., Herceg Z., Swerdlow A.J., Vineis P., Flanagan J.M., Johansson A., Palli D., Masala G., Grioni S., Agnoli C., Tumino R., Giurdanella M.C., Fasanelli F., Sacerdote C., Panico S., Mattiello A., Polidoro S., Jones M.E., Schoemaker M.J., Orr N., Tomczyk K., Johnson N., Fletcher O., Perduca V., Baglietto L., Chajes V., Dugue P.-A., Southey M.C., Giles G.G., English D.R., Milne R.L., Severi G., Ambatipudi S., Cuenin C., Romieu I., Herceg Z., Swerdlow A.J., Vineis P., Flanagan J.M., Johansson A., Palli D., Masala G., Grioni S., Agnoli C., Tumino R., Giurdanella M.C., Fasanelli F., Sacerdote C., Panico S., Mattiello A., Polidoro S., Jones M.E., Schoemaker M.J., Orr N., Tomczyk K., Johnson N., Fletcher O., Perduca V., and Baglietto L.
- Abstract
Background: It is well established that estrogens and other hormonal factors influence breast cancer susceptibility. We hypothesized that a woman's total lifetime estrogen exposure accumulates changes in DNA methylation, detectable in the blood, which could be used in risk assessment for breast cancer. Method(s): An estimated lifetime estrogen exposure (ELEE) model was defined using epidemiological data from EPIC-Italy (n = 31,864). An epigenome-wide association study (EWAS) of ELEE was performed using existing Illumina HumanMethylation450K Beadchip (HM450K) methylation data obtained from EPIC-Italy blood DNA samples (n = 216). A methylation index (MI) of ELEE based on 31 CpG sites was developed using HM450K data from EPIC-Italy and the Generations Study and evaluated for association with breast cancer risk in an independent dataset from the Generations Study (n = 440 incident breast cancer cases matched to 440 healthy controls) using targeted bisulfite sequencing. Lastly, a meta-analysis was conducted including three additional cohorts, consisting of 1187 case-control pairs. Result(s): We observed an estimated 5% increase in breast cancer risk per 1-year longer ELEE (OR = 1.05, 95% CI 1.04-1.07, P = 3 x 10-12) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data (ORQ4-vs-Q1 = 1.77, 95% CI 1.07-2.93, P = 0.027) and in the meta-analysis (ORQ4-vs-Q1 = 1.43, 95% CI 1.05-2.00, P = 0.024); however, the correlation between the MI and ELEE was not validated across study cohorts. Conclusion(s): We have identified a blood DNA methylation signature associated with breast cancer risk in this study. Further investigation is required to confirm the interaction between estrogen exposure and DNA methylation in the blood.Copyright © 2019 The Author(s).
- Published
- 2019
15. Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk
- Author
-
Johansson, A, Palli, D, Masala, G, Grioni, S, Agnoli, C, Tumino, R, Giurdanella, MC, Fasanelli, F, Sacerdote, C, Panico, S, Mattiello, A, Polidoro, S, Jones, ME, Schoemaker, MJ, Orr, N, Tomczyk, K, Johnson, N, Fletcher, O, Perduca, V, Baglietto, L, Dugue, P-A, Southey, MC, Giles, GG, English, DR, Milne, RL, Severi, G, Ambatipudi, S, Cuenin, C, Chajes, V, Romieu, I, Herceg, Z, Swerdlow, AJ, Vineis, P, Flanagan, JM, Johansson, A, Palli, D, Masala, G, Grioni, S, Agnoli, C, Tumino, R, Giurdanella, MC, Fasanelli, F, Sacerdote, C, Panico, S, Mattiello, A, Polidoro, S, Jones, ME, Schoemaker, MJ, Orr, N, Tomczyk, K, Johnson, N, Fletcher, O, Perduca, V, Baglietto, L, Dugue, P-A, Southey, MC, Giles, GG, English, DR, Milne, RL, Severi, G, Ambatipudi, S, Cuenin, C, Chajes, V, Romieu, I, Herceg, Z, Swerdlow, AJ, Vineis, P, and Flanagan, JM
- Abstract
BACKGROUND: It is well established that estrogens and other hormonal factors influence breast cancer susceptibility. We hypothesized that a woman's total lifetime estrogen exposure accumulates changes in DNA methylation, detectable in the blood, which could be used in risk assessment for breast cancer. METHODS: An estimated lifetime estrogen exposure (ELEE) model was defined using epidemiological data from EPIC-Italy (n = 31,864). An epigenome-wide association study (EWAS) of ELEE was performed using existing Illumina HumanMethylation450K Beadchip (HM450K) methylation data obtained from EPIC-Italy blood DNA samples (n = 216). A methylation index (MI) of ELEE based on 31 CpG sites was developed using HM450K data from EPIC-Italy and the Generations Study and evaluated for association with breast cancer risk in an independent dataset from the Generations Study (n = 440 incident breast cancer cases matched to 440 healthy controls) using targeted bisulfite sequencing. Lastly, a meta-analysis was conducted including three additional cohorts, consisting of 1187 case-control pairs. RESULTS: We observed an estimated 5% increase in breast cancer risk per 1-year longer ELEE (OR = 1.05, 95% CI 1.04-1.07, P = 3 × 10-12) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data (ORQ4_vs_Q1 = 1.77, 95% CI 1.07-2.93, P = 0.027) and in the meta-analysis (ORQ4_vs_Q1 = 1.43, 95% CI 1.05-2.00, P = 0.024); however, the correlation between the MI and ELEE was not validated across study cohorts. CONCLUSION: We have identified a blood DNA methylation signature associated with breast cancer risk in this study. Further investigation is required to confirm the interaction between estrogen exposure and DNA methylation in the blood.
- Published
- 2019
16. Poly(carbonate‐urea‐urethane) networks exhibiting high‐strain shape‐memory effect
- Author
-
Mazurek-Budzynska, M., Razzaq, M.Y., Tomczyk, K., Rokicki, G., Behl, M., and Lendlein, A.
- Abstract
A challenge in the design of shape-memory polymers (SMPs) is to achieve high deformability with a simultaneous high shape recovery ratio. Here we explored, whether SMPs featuring large deformation capability and high shape recovery ratios can be created as polymer networks providing two kinds of netpoints based on covalent bonds and physical interactions. As a model system, we selected poly(carbonate-urea-urethane)s (PCUUs) synthesized by a precursor route, based on oligo(alkylene carbonate) diols, isophorone diisocyanate (IPDI), and water vapor. The PCUU networks exhibited a one-way shape-memory effect (1W-SME) with programmed strains up to εprog = 1000% whereby they provided excellent shape fixity (92–97%) and shape recovery (≥99%) ratios. The switching temperatures (Tsw) varied between 36 and 65 °C and increased with the increasing molecular weight of the oligo(alkylene carbonate) diol and length of the hydrocarbon chain between the carbonate linkages. Tsw was also influenced by the strain applied during programming (εprog). Poly(carbonate-urethane)s have been reported to have good biocompatibility and biostability, which in the combination of high-strain capacity and high Young\'s modulus makes the obtained PCUUs interesting candidate materials suitable for medical devices such as medical sutures or vascular stents.
- Published
- 2017
17. Abstract P1-04-01: Epigenome-wide association study for breast cancer risk using whole genome and target captured bisulphite sequencing: A pooled case-control study nested in the breakthrough generations study
- Author
-
Flanagan, JM, primary, Curry, E, additional, Stirling, L, additional, Flower, K, additional, Orr, N, additional, Tomczyk, K, additional, Coulson, P, additional, Jones, M, additional, Ashworth, A, additional, Swerdlow, A, additional, Brown, R, additional, and Garcia-Closas, M, additional
- Published
- 2017
- Full Text
- View/download PDF
18. Bioinformatics Study of Structural Patterns in Plant MicroRNA Precursors
- Author
-
Miskiewicz, J., primary, Tomczyk, K., additional, Mickiewicz, A., additional, Sarzynska, J., additional, and Szachniuk, M., additional
- Published
- 2017
- Full Text
- View/download PDF
19. Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk
- Author
-
Orr, N., Lemnrau, A., Cooke, R., Fletcher, O., Tomczyk, K., Jones, M., Johnson, N., Lord, C. J., Mitsopoulos, C, Zvelebil, M., McDade, S. S., Buck, G., Blancher, C., Trainer, A. H., James, P. A., Bojesen, S. E., Bokm, S., Nevanlinna, H., Mattson, J., Friedman, E, Laitman, Y., Palli, D., Masala, G., Zanna, I., Ottini, L., Giannini, G., Hollestelle, A., Van Den Ouwel, A. M. W., Novaković, S., Krajc, M., Gago Dominguez, Manuela, Castelao Fernández, José Esteban, Olsson, H., Hedenfalk, I., Easton, D. F., Pharoah, P. D. P., Dunning, A. M., Bishop, D. T., Neuhausen, S. L., Steele, L., Houlston, R. S., Garcia-Closas, M., Ashworth, A., and Swerdlow, A. J.
- Subjects
Chromosomes, Human, Pair 14 ,DNA-Binding Proteins ,Male ,Neoplasias de la Mama Masculina ,Risk Factors ,European Continental Ancestry Group ,Proteínas de Unión al ADN ,Humans ,Genetic Predisposition to Disease ,Polymorphism, Single Nucleotide ,Breast Neoplasms, Male ,Genome-Wide Association Study ,Estudio de Asociación del Genoma Completo - Abstract
We conducted a genome-wide association study of male breast cancer comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (P = 3.02 × 10-13; odds ratio (OR) = 1.57). We also refine association at 16q12.1 to a SNP within TOX3 (P = 3.87 × 10-15; OR = 1.50). Instituto de Salud Carlos III/Programa Grupos Emergentes
- Published
- 2012
20. Polish energy sector in order to reaching the standings of european union climate and energy policy
- Author
-
Tomczak, T., Daros, A., Tomczyk, K., and Cieciura, K.
- Published
- 2012
21. Potential-controlled rotaxane molecular shuttles based on electron-deficient macrocyclic complexes
- Author
-
Woźny, M., primary, Pawłowska, J., additional, Tomczyk, K. M., additional, Bilewicz, R., additional, and Korybut-Daszkiewicz, B., additional
- Published
- 2014
- Full Text
- View/download PDF
22. Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk
- Author
-
Orr, N, Lemnrau, A, Cooke, R, Fletcher, O, Tomczyk, K, Jones, M, Johnson, N, Lord, CJ, Mitsopoulos, C, Zvelebil, M, McDade, SS, Buck, G, Blancher, C, Trainer, AH, James, PA, Bojesen, SE, Bokmand, S, Nevanlinna, H, Mattson, J, Friedman, E, Laitman, Y, Palli, D, Masala, G, Zanna, I, Ottini, L, Giannini, G, Hollestelle, A, van den Ouweland, AMW, Novakovic, S, Krajc, M, Gago-Dominguez, M, Castelao, JE, Olsson, H, Hedenfalk, I, Easton, DF, Pharoah, PDP, Dunning, AM, Bishop, DT, Neuhausen, SL, Steele, L, Houlston, RS, Garcia-Closas, M, Ashworth, A, Swerdlow, AJ, Orr, N, Lemnrau, A, Cooke, R, Fletcher, O, Tomczyk, K, Jones, M, Johnson, N, Lord, CJ, Mitsopoulos, C, Zvelebil, M, McDade, SS, Buck, G, Blancher, C, Trainer, AH, James, PA, Bojesen, SE, Bokmand, S, Nevanlinna, H, Mattson, J, Friedman, E, Laitman, Y, Palli, D, Masala, G, Zanna, I, Ottini, L, Giannini, G, Hollestelle, A, van den Ouweland, AMW, Novakovic, S, Krajc, M, Gago-Dominguez, M, Castelao, JE, Olsson, H, Hedenfalk, I, Easton, DF, Pharoah, PDP, Dunning, AM, Bishop, DT, Neuhausen, SL, Steele, L, Houlston, RS, Garcia-Closas, M, Ashworth, A, and Swerdlow, AJ
- Abstract
We conducted a genome-wide association study of male breast cancer comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (P = 3.02 × 10(-13); odds ratio (OR) = 1.57). We also refine association at 16q12.1 to a SNP within TOX3 (P = 3.87 × 10(-15); OR = 1.50).
- Published
- 2012
23. Abstract P3-08-04: Impact of CYP3A variation on estrone levels and breast cancer risk
- Author
-
Ross, GM, primary, Johnson, N, additional, Orr, N, additional, Walker, K, additional, Gibson, L, additional, Folkerd, E, additional, Haynes, B, additional, Palles, C, additional, Coupland, B, additional, Shoemaker, M, additional, Jones, M, additional, Broderick, P, additional, Sawyer, E, additional, Kerin, M, additional, Tomlinson, I, additional, Zvelebil, M, additional, Chilcott-Burns, S, additional, Tomczyk, K, additional, Simpson, G, additional, Willianson, J, additional, Hillier, S, additional, Houlston, R, additional, Swerdlow, A, additional, Ashworth, A, additional, Dowsett, M, additional, Peto, J, additional, dos Santos, I, additional, and Fletcher, O, additional
- Published
- 2012
- Full Text
- View/download PDF
24. Clinical models are inaccurate in predicting bile duct stones in situ for patients with gallbladder
- Author
-
Topal, B., primary, Fieuws, S., additional, Tomczyk, K., additional, Aerts, R., additional, Van Steenbergen, W., additional, Verslype, C., additional, and Penninckx, F., additional
- Published
- 2008
- Full Text
- View/download PDF
25. Laparoscopical Repair.
- Author
-
Schumpelick, Volker, Fitzgibbons, Robert J., Miserez, M., Tomczyk, K., Penninckx, F., Elieson, M. J., Whitaker, J. M., LeBlanc, K. A., Berger, D., Bientzle, M., Kukleta, Jan F., and Ramshaw, B.
- Abstract
The incidence of incisional hernias after major abdominal surgery persists at around 20%, implicating the need of a safe and effective technique for repair [7, 23]. Today the need of meshes for augmentation of the abdominal wall is generally accepted because the hernia disease can be explained by a pathological scar formation [16]. The mostly recommended open sublay technique needs separation of the different layers of the abdominal wall, explaining the sometimes high rates of complications reported in the literature [11, 15, 22, 24]. Therefore the laparoscopic approach gains increasing acceptance. It has been generally demonstrated that the rate of wound complications is dramatically decreased after laparoscopic procedures [17, 22, 24, 25]. However, besides the possible complication of unrecognized enterotomy the recurrence rate is still under debate. Since the widespread application of the method the recurrence rates seem to be increasing sometimes exceeding 10% [1-6, 8-10, 13, 17, 22, 26]. The presentation should summarize our experience after more than 600 laparoscopic procedures done for incisional, umbilical, epigastric and parastomal hernias in terms of the reasons for recurrences as well as the treatment of this complication. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
26. Impact of CYP3A variation on estrone levels and breast cancer risk.
- Author
-
Ross, G. M., Johnson, N., Orr, N., Walker, K., Gibson, L., Folkerd, E., Haynes, B., Palles, C., Coupland, B., Shoemaker, M., Jones, M., Broderick, P., Sawyer, E., Kerin, M., Tomlinson, I., Zvelebil, M., Chilcott-Burns, S., Tomczyk, K., Simpson, G., and Willianson, J.
- Subjects
- *
STEROIDS , *BREAST cancer etiology , *PREGNANEDIOL , *BREAST cancer risk factors , *TAMOXIFEN - Abstract
Background: Epidemiological studies provide strong evidence fora role of endogenous sex steroids in the etiology of breast cancer. Our aim was to identify common variants in genes involved in sex steroid synthesis or metabolism that were associated with premenopausal hormone levels and breast cancer risk. Methods: We measured urinary estrone glucuronide (E1G) and pregnanediol glucuronide (PG) using a protocol specifically developed to account for cyclic variation in hormone levels during the menstrual cycle, plasma sex hormone-binding globulin (SHBG) and androgenic precursors in up to 763 healthy premenopausal women. We genotyped 642 single nucleotide polymorphisms (SNPs) in these women; a single SNP was further tested for association with breast cancer risk in data from 10,551 breast cancer case patients and 17,535 control subjects. All statistical tests were two-sided. Results: rs10273424 mapping approximately 50kb centromericto the cytochrome P450 3A (CYP3A) cluster (7q22.1) was associated with a 21.8% reduction in E1G levels (P = 2.7 x 10-9) and a modest reduction in breast cancer risk in cases diagnosed at or before age 50 (OR = 0.91; P = 0.03) but not older cases (odds ratio (OR) = 1.01; P = 0.82). A rare non-synonymous SHBG SNP was associated with reduced plasma SHBG levels. Conclusions: Genetic variation in non-coding sequences flanking the CYP3A locus contributes to variance in premenopausal E1G levels and breast cancer risk in younger cases. Since CYP3A4, the most predominantly expressed CYP3A gene, is responsible for metabolism of endogenous and exogenous hormones and hormonal agents such as tamoxifen, used in the treatment of breast cancer this association may have wider implications. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
27. Incorporation of Anions into Anodic Alumina-A New Track in Cr(VI) Anodizing Substitution?
- Author
-
Tomczyk K and Stępniowski WJ
- Abstract
Aluminum technical alloys are well known for their outstanding mechanical properties, especially after heat treatment. However, quenching and aging, which improve the mechanical properties, by the formation of Cu-rich zones and phases that are coherent with the matrix and block the dislocation motion, cause uneven distribution of the elements in the alloy and consequently make it prone to corrosion. One method providing satisfactory corrosion protection of aluminum alloys is anodizing. On an industrial scale, it is usually carried out in electrolytes containing chromates that were found to be cancerogenic and toxic. Therefore, much effort has been undertaken to find substitutions. Currently, there are many Cr(VI)-free substitutes like tartaric-sulfuric acid anodizing or citric-sulfuric acid anodizing. Despite using such approaches even on the industrial scale, Cr(VI)-based anodizing still seems to be superior; therefore, there is an urge to find more complex but more effective approaches in anodizing. The incorporation of anions into anodic alumina from the electrolytes is a commonly known effect. Researchers used this phenomenon to entrap various other anions and organic compounds into anodic alumina to change their properties. In this review paper, the impact of the incorporation of various corrosion inhibitors into anodic alumina on the corrosion performance of the alloys is discussed. It is shown that Mo compounds are promising, especially when combined with organic acids.
- Published
- 2024
- Full Text
- View/download PDF
28. Safety of Progestogen Hormonal Contraceptive Methods during Lactation: An Overview.
- Author
-
Chmaj-Wierzchowska K, Wszołek K, Tomczyk K, and Wilczak M
- Abstract
Background: Breastfeeding is a process for not only nourishing infants but also for building a unique emotional bond between mother and child. Therefore, the ideal contraception during lactation should not affect lactation (milk composition, milk volume) and offspring development., Objectives: This study aims to analyze the literature on the safety of progestogen hormonal contraceptive methods during lactation., Methods: We conducted a thorough search across various databases, including the National Library of Medicine (PubMed), and the Cochrane Database, Drugs and Lactation Database (LactMed). Our search utilized specific phrases such as: "lactation" and "breastfeeding" and "oral contraception" with "drospirenone" or "desogestrel", with "subcutaneous etonogestrel implant" or "etonogestrel implant", with "levonorgestrel-releasing intrauterine system", and "emergency contraception", with "levonorgestrel" or "ulipristal acetate"., Conclusions: Based on published scientific reports, progestogen hormonal contraceptives can be considered a relatively safe solution for women desiring to continue feeding their infant with their milk while using hormonal contraception. It is important to seek guidance on selecting the best contraception method based on the latest medical knowledge, tailored to the individual needs and clinical circumstances of each woman and place of residence. A woman should always be informed of the potential risks of such a treatment and then allowed to make her own decision based on the knowledge received from a specialist.
- Published
- 2024
- Full Text
- View/download PDF
29. Quality of Life of Women with Polycystic Ovary Syndrome.
- Author
-
Ligocka N, Chmaj-Wierzchowska K, Wszołek K, Wilczak M, and Tomczyk K
- Subjects
- Humans, Female, Quality of Life psychology, Polycystic Ovary Syndrome complications, Hyperandrogenism, Infertility, Female, Insulin Resistance
- Abstract
Background and Objectives : Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by multiple hormonal and metabolic abnormalities, including insulin resistance, hyperandrogenism, and disturbances in lipid and carbohydrate metabolism. The objective of this study is to assess the quality of life of women diagnosed with polycystic ovary syndrome (PCOS) and to identify any factors within the study group that may impact the scores related to quality of life. Materials and Methods : This research was carried out among women diagnosed with PCOS. An original questionnaire, developed through an online Google Forms survey, was utilized as the research instrument and distributed through social networks and support groups to women facing PCOS. This study encompassed a participant pool of 200 women with PCOS, aged 24 years or older. For the analytical component, Pearson's χ
2 test was employed-a nonparametric test designed to assess the relationship between two variables measured on a qualitative scale. The chosen level of statistical significance was set at p < 0.05. Results : The analysis revealed that the quality of life of the women under study was not linked to the duration of the disease or comorbidities. However, a significant association was observed with the inconvenience caused by PCOS symptoms. Women experiencing very bothersome symptoms of PCOS reported a lower quality of life compared to those with symptoms rated as not very bothersome. Despite the majority of women with PCOS rating their quality of life as good or very good, they often find the associated symptoms of PCOS bothersome. Women reporting lower quality of life tend to acknowledge the impact of PCOS on their lives, experience a sense of lack of control over the disease, struggle with depression, and do not accept their physical appearance. Conclusions : Hence, the support from specialists like endocrinologists, gynecologists, and nutritionists becomes crucial for many women dealing with PCOS. Adopting a healthy lifestyle, incorporating a balanced diet, and engaging in regular physical activity can assist in managing the troublesome symptoms of PCOS, thereby enhancing overall quality of life. In instances of emotional difficulties, seeking psychological support is equally important, and the significance of support and acceptance from loved ones should not be overlooked.- Published
- 2024
- Full Text
- View/download PDF
30. Factors Affecting Women's Assessment and Satisfaction with Their Childbirth.
- Author
-
Konieczka J, Tomczyk K, Wilczak M, and Chmaj-Wierzchowska K
- Subjects
- Humans, Female, Pregnancy, Meals, Medical Staff, Pain Management, Labor, Obstetric, Music
- Abstract
Background and Objective: Childbirth is one of the most significant experiences in a woman's life. The manner in which childbirth unfolds and is experienced can be influenced by various factors, including the birthing environment and the woman's attitude and preparation. Taking a holistic view of childbirth, it becomes apparent that addressing the basic physiological needs during childbirth can significantly influence the comfort and sense of security of laboring women. The aim of this research was to assess the level of satisfaction among women with their experience during childbirth and to identify its determinants. Materials and Methods: This study included 275 women who had given birth within the past 15 years and were up to 40 years of age. The research method employed was a diagnostic survey, involving a self-designed questionnaire. Results: discussing the birth plan with the midwife, the ability to ask questions during labor, consuming meals during labor, water immersion, listening to music during labor, assuming vertical positions during the second stage of labor, and skin-to-skin contact are associated with increased satisfaction with the childbirth experience. Conclusions: The study findings revealed that the highest levels of satisfaction were reported in connection with the interactions with medical staff during childbirth and the quality of facilities available during delivery. Conversely, the lowest levels of satisfaction were associated with the possibility of using pain relief methods during labor.
- Published
- 2024
- Full Text
- View/download PDF
31. A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry.
- Author
-
Middha P, Wang X, Behrens S, Bolla MK, Wang Q, Dennis J, Michailidou K, Ahearn TU, Andrulis IL, Anton-Culver H, Arndt V, Aronson KJ, Auer PL, Augustinsson A, Baert T, Freeman LEB, Becher H, Beckmann MW, Benitez J, Bojesen SE, Brauch H, Brenner H, Brooks-Wilson A, Campa D, Canzian F, Carracedo A, Castelao JE, Chanock SJ, Chenevix-Trench G, Cordina-Duverger E, Couch FJ, Cox A, Cross SS, Czene K, Dossus L, Dugué PA, Eliassen AH, Eriksson M, Evans DG, Fasching PA, Figueroa JD, Fletcher O, Flyger H, Gabrielson M, Gago-Dominguez M, Giles GG, González-Neira A, Grassmann F, Grundy A, Guénel P, Haiman CA, Håkansson N, Hall P, Hamann U, Hankinson SE, Harkness EF, Holleczek B, Hoppe R, Hopper JL, Houlston RS, Howell A, Hunter DJ, Ingvar C, Isaksson K, Jernström H, John EM, Jones ME, Kaaks R, Keeman R, Kitahara CM, Ko YD, Koutros S, Kurian AW, Lacey JV, Lambrechts D, Larson NL, Larsson S, Le Marchand L, Lejbkowicz F, Li S, Linet M, Lissowska J, Martinez ME, Maurer T, Mulligan AM, Mulot C, Murphy RA, Newman WG, Nielsen SF, Nordestgaard BG, Norman A, O'Brien KM, Olson JE, Patel AV, Prentice R, Rees-Punia E, Rennert G, Rhenius V, Ruddy KJ, Sandler DP, Scott CG, Shah M, Shu XO, Smeets A, Southey MC, Stone J, Tamimi RM, Taylor JA, Teras LR, Tomczyk K, Troester MA, Truong T, Vachon CM, Wang SS, Weinberg CR, Wildiers H, Willett W, Winham SJ, Wolk A, Yang XR, Zamora MP, Zheng W, Ziogas A, Dunning AM, Pharoah PDP, García-Closas M, Schmidt MK, Kraft P, Milne RL, Lindström S, Easton DF, and Chang-Claude J
- Subjects
- Adult, Female, Humans, Genetic Predisposition to Disease, Bayes Theorem, Genome-Wide Association Study, Risk Factors, Polymorphism, Single Nucleotide, Case-Control Studies, Gene-Environment Interaction, Breast Neoplasms etiology, Breast Neoplasms genetics
- Abstract
Background: Genome-wide studies of gene-environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer., Methods: Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs., Results: Assuming a 1 × 10
-5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94)., Conclusions: Overall, the contribution of G×E interactions to the heritability of breast cancer is very small. At the population level, multiplicative G×E interactions do not make an important contribution to risk prediction in breast cancer., (© 2023. BioMed Central Ltd., part of Springer Nature.)- Published
- 2023
- Full Text
- View/download PDF
32. Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival.
- Author
-
Morra A, Schreurs MAC, Andrulis IL, Anton-Culver H, Augustinsson A, Beckmann MW, Behrens S, Bojesen SE, Bolla MK, Brauch H, Broeks A, Buys SS, Camp NJ, Castelao JE, Cessna MH, Chang-Claude J, Chung WK, Colonna SV, Couch FJ, Cox A, Cross SS, Czene K, Daly MB, Dennis J, Devilee P, Dörk T, Dunning AM, Dwek M, Easton DF, Eccles DM, Eriksson M, Evans DG, Fasching PA, Fehm TN, Figueroa JD, Flyger H, Gabrielson M, Gago-Dominguez M, García-Closas M, García-Sáenz JA, Genkinger J, Grassmann F, Gündert M, Hahnen E, Haiman CA, Hamann U, Harrington PA, Hartikainen JM, Hoppe R, Hopper JL, Houlston RS, Howell A, Jakubowska A, Janni W, Jernström H, John EM, Johnson N, Jones ME, Kristensen VN, Kurian AW, Lambrechts D, Le Marchand L, Lindblom A, Lubiński J, Lux MP, Mannermaa A, Mavroudis D, Mulligan AM, Muranen TA, Nevanlinna H, Nevelsteen I, Neven P, Newman WG, Obi N, Offit K, Olshan AF, Park-Simon TW, Patel AV, Peterlongo P, Phillips KA, Plaseska-Karanfilska D, Polley EC, Presneau N, Pylkäs K, Rack B, Radice P, Rashid MU, Rhenius V, Robson M, Romero A, Saloustros E, Sawyer EJ, Schmutzler RK, Schuetze S, Scott C, Shah M, Smichkoska S, Southey MC, Tapper WJ, Teras LR, Tollenaar RAEM, Tomczyk K, Tomlinson I, Troester MA, Vachon CM, van Veen EM, Wang Q, Wendt C, Wildiers H, Winqvist R, Ziogas A, Hall P, Pharoah PDP, Adank MA, Hollestelle A, Schmidt MK, and Hooning MJ
- Subjects
- Female, Humans, Checkpoint Kinase 2 genetics, Genetic Predisposition to Disease, Germ-Line Mutation, Heterozygote, Proportional Hazards Models, Breast Neoplasms genetics, Breast Neoplasms radiotherapy
- Abstract
Background: Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers., Aim: To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS., Methods: Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death., Results: There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09-1.56)]., Conclusion: Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
33. New Possibilities for Hormonal Vaginal Treatment in Menopausal Women.
- Author
-
Tomczyk K, Chmaj-Wierzchowska K, Wszołek K, and Wilczak M
- Abstract
Hormonal vaginal therapy is an effective treatment option for women who experience vaginal symptoms related to hormonal changes. Estrogen and prasterone are widely used as vaginal treatments, particularly for urogenital atrophy. These symptoms may include vaginal dryness, itching, burning, and pain during sexual intercourse, all of which can significantly affect a woman's quality of life. Previous studies have indicated that such treatment improves tissue elasticity, moisturizes the vagina, and can have a substantial impact on urine incontinence and vaginal microflora and decreases dyspareunia. Hormonal therapy is also useful and commonly used before vaginal surgical treatment. Prasterone is quite a new option for vaginal therapy in Poland and is mainly recommended for dyspareunia in menopausal women. The study related to prasterone therapy emphasizes its effectiveness and safety, making it advantageous to explore its beneficial impact. This paperwork aims to summarize the mechanism of action as well as the effects of both drugs and their beneficial action during vaginal treatment.
- Published
- 2023
- Full Text
- View/download PDF
34. Procedure Proposal for Minimising the Dynamic Error of Second-Order Sensors.
- Author
-
Tomczyk K, Kowalczyk M, and Ostrowska K
- Subjects
- Monte Carlo Method, Records, Signal Processing, Computer-Assisted
- Abstract
This paper proposes the procedure for minimising the dynamic error in the time and frequency domains, based on the example of a second-order sensor. Our procedure includes three main steps: modelling of the sensors using the Monte Carlo (MC) method; determination of the maximum value of the dynamic error using the integral-square criterion (ISC); and optimisation of the parameters of the sensor model by minimising the ISC. The uncertainties associated with the modelling procedure and the MC method are also considered. The mathematical formulae necessary for implementation in a given programming language (MathCad, MATLAB, C, etc.) are presented in detail. The proposed procedure was implemented in the frequency domain, using MathCad 15, and applied to the example of the Althen 731-207 accelerometer. Validation of the proposed procedure was carried out using a digital signal processor of type TMS320C6713. The proposed procedure can increase the accuracy of the signal processing obtained at the output of sensors applied to a wide range of measurements.
- Published
- 2022
- Full Text
- View/download PDF
35. How does the Selection of Laboratory Mice Affect the Results of Physiological Distribution of Radiopharmaceuticals?
- Author
-
Karczmarczyk U, Ochniewicz P, Laszuk E, Tomczyk K, and Garnuszek P
- Subjects
- Animals, Mice, Mice, Inbred BALB C, Radioisotopes, Radiopharmaceuticals pharmacology
- Abstract
Background: The choice of mice strain can significantly influence the physiological distribution and may lead to an inadequate assessment of the radiopharmaceutical properties., Objective: This work aims to present how the legal requirements that apply to radiopharmaceuticals contained in the various guidelines determine the choice of the mouse strain for quality control and preclinical studies and affect the results of physiological distribution., Methods: Swiss and BALB/c mice were chosen as commonly used strains in experiments for research and quality control purposes. Radiopharmaceuticals, i.e., preparations containing one or more radioactive isotopes in their composition, are subject to the same legal regulations at every stage of the research, development and routine quality control as all other medicines. Therefore, in vivo experiments are to be carried out to confirm the pharmacological properties and safety. Moreover, if a radiopharmaceutical's chemical structure is unknown or complex and impossible to be determined by physicochemical methods, an analysis of physiological distribution in a rodent animal model needs to be performed., Results: In our studies, thirty-six mice (Swiss n=18, BALB/c n=18) were randomly divided into six groups and injected with the following radiopharmaceuticals: [
99m Tc]Tc-Colloid, [99m Tc]Tc-DTPA and [99m Tc]Tc-EHIDA. Measurement of physiological distribution was conducted following the requirements of European Pharmacopoeia (Ph. Eur.) monograph 0689, internal instructions and the United States Pharmacopeia (USP) monograph. Additionally, at preclinical studies, ten mice (Swiss n=5, BALB/c n=5) were injected with the new tracer [99m Tc]Tc-PSMA-T4, and its physiological distribution has been compared. The p-value <0.05 proved the statistical significance of the radiopharmaceutical physiological distribution., Conclusion: We claim that mice strain choice can significantly influence the physiological distribution and may lead to inaccurate quality control results and incomprehensible interpretation of the results from preclinical in vivo studies of a new radiopharmaceutical., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)- Published
- 2022
- Full Text
- View/download PDF
36. Women's Healthcare Services since the COVID-19 Pandemic Outbreak in Poland.
- Author
-
Wszołek K, Pruski D, Tomczyk K, Kampioni M, Chmaj-Wierzchowska K, Przybylski M, and Wilczak M
- Subjects
- Delivery of Health Care, Female, Humans, Pandemics, Poland epidemiology, Pregnancy, SARS-CoV-2, COVID-19, Maternal Health Services
- Abstract
The COVID-19 pandemic had a direct impact on the extent of guaranteed healthcare services. Many gynecologists', obstetricians', and midwives' offices were closed, laboratories suspended their activities, the collection of necessary tests was delayed, and women had to wait much longer for test results than they had to previously. General women's healthcare prophylactic programs were suspended or delayed. In 2020, screening financed by public funds covered less than one-seventh of the female population in Poland. As medical teams, professionals, clinicians, and scientists, we have been facing a challenge to help, protect, and care for one of the most vulnerable population groups, pregnant women. A significant part of that challenge has been in preventing the spread of severe COVID-19, along with other preventable diseases, among women who are pregnant, who are in labor, or who have recently given birth.
- Published
- 2021
- Full Text
- View/download PDF
37. Medical conferences in the era of environmental conscientiousness and a global health crisis: The carbon footprint of presenter flights to pre-COVID pediatric urology conferences and a consideration of future options.
- Author
-
Milford K, Rickard M, Chua M, Tomczyk K, Gatley-Dewing A, and Lorenzo AJ
- Subjects
- Carbon Footprint, Child, Global Health, Humans, Pandemics, Retrospective Studies, SARS-CoV-2, COVID-19, Urology
- Abstract
Introduction: Medical conferences are integral to academic medicine, with academic posters being a well-established medium for presenting research. However, conferences carry an ecological footprint due to greenhouse gas emissions. Furthermore, traditional conference formats have recently not been possible due to the COVID-19 pandemic. Herein we examine the carbon footprint associated with travel by presenting delegates to the Fall SPU conferences from 2013 to 2019, and the 2015 ESPU conference., Methods: Online programs for the targeted SPU Fall meetings and the 2015 ESPU Annual Meeting were retrospectively reviewed. Variables collected included meeting location and presenter home base. Distance traveled by the presenter, and likely CO
2 e of this return trip were estimated using online calculators. Analysis was performed using the Kruskal-Wallis-H test with pairwise comparisons to detect differences in round trip distances and CO2 e between meeting locations., Results: Six Fall SPU conferences and one ESPU conference were reviewed. The majority of presenters were from the region (North America and Europe, respectively), for both SPU and ESPU. The median round trip distance was 2596.34 miles (IQR 1420.96-4438.30), and the median CO2 e 0.61 metric tons (IQR 0.36-1.02). We found that the distances traveled to conferences in the Western USA and Europe were slightly further than those to conferences in Central Canada and the Southern US. The difference in CO2 e between these locations did not achieve statistical significance., Conclusion: Presenter travel to and from pediatric urological conferences generates an important carbon footprint and may not be possible in the medium-term future due to a global pandemic. We should explore strategies to allow meetings and knowledge exchange to continue whilst reducing the need for travel and the ecological burden of conferences., Level of Evidence: Level III: Most comparative level of evidence., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF
38. Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element.
- Author
-
Baxter JS, Johnson N, Tomczyk K, Gillespie A, Maguire S, Brough R, Fachal L, Michailidou K, Bolla MK, Wang Q, Dennis J, Ahearn TU, Andrulis IL, Anton-Culver H, Antonenkova NN, Arndt V, Aronson KJ, Augustinsson A, Becher H, Beckmann MW, Behrens S, Benitez J, Bermisheva M, Bogdanova NV, Bojesen SE, Brenner H, Brucker SY, Cai Q, Campa D, Canzian F, Castelao JE, Chan TL, Chang-Claude J, Chanock SJ, Chenevix-Trench G, Choi JY, Clarke CL, Colonna S, Conroy DM, Couch FJ, Cox A, Cross SS, Czene K, Daly MB, Devilee P, Dörk T, Dossus L, Dwek M, Eccles DM, Ekici AB, Eliassen AH, Engel C, Fasching PA, Figueroa J, Flyger H, Gago-Dominguez M, Gao C, García-Closas M, García-Sáenz JA, Ghoussaini M, Giles GG, Goldberg MS, González-Neira A, Guénel P, Gündert M, Haeberle L, Hahnen E, Haiman CA, Hall P, Hamann U, Hartman M, Hatse S, Hauke J, Hollestelle A, Hoppe R, Hopper JL, Hou MF, Ito H, Iwasaki M, Jager A, Jakubowska A, Janni W, John EM, Joseph V, Jung A, Kaaks R, Kang D, Keeman R, Khusnutdinova E, Kim SW, Kosma VM, Kraft P, Kristensen VN, Kubelka-Sabit K, Kurian AW, Kwong A, Lacey JV, Lambrechts D, Larson NL, Larsson SC, Le Marchand L, Lejbkowicz F, Li J, Long J, Lophatananon A, Lubiński J, Mannermaa A, Manoochehri M, Manoukian S, Margolin S, Matsuo K, Mavroudis D, Mayes R, Menon U, Milne RL, Mohd Taib NA, Muir K, Muranen TA, Murphy RA, Nevanlinna H, O'Brien KM, Offit K, Olson JE, Olsson H, Park SK, Park-Simon TW, Patel AV, Peterlongo P, Peto J, Plaseska-Karanfilska D, Presneau N, Pylkäs K, Rack B, Rennert G, Romero A, Ruebner M, Rüdiger T, Saloustros E, Sandler DP, Sawyer EJ, Schmidt MK, Schmutzler RK, Schneeweiss A, Schoemaker MJ, Shah M, Shen CY, Shu XO, Simard J, Southey MC, Stone J, Surowy H, Swerdlow AJ, Tamimi RM, Tapper WJ, Taylor JA, Teo SH, Teras LR, Terry MB, Toland AE, Tomlinson I, Truong T, Tseng CC, Untch M, Vachon CM, van den Ouweland AMW, Wang SS, Weinberg CR, Wendt C, Winham SJ, Winqvist R, Wolk A, Wu AH, Yamaji T, Zheng W, Ziogas A, Pharoah PDP, Dunning AM, Easton DF, Pettitt SJ, Lord CJ, Haider S, Orr N, and Fletcher O
- Subjects
- Breast Neoplasms genetics, CRISPR-Cas Systems, Cell Line, Chromosome Mapping, Chromosomes, Human, Pair 2, Female, Genetic Association Studies, Genetic Variation, Humans, Risk Factors, Sequence Deletion, Insulin-Like Growth Factor Binding Protein 5 genetics, Molecular Sequence Annotation, Promoter Regions, Genetic
- Abstract
A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10
-31 )., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF
39. Design and Evaluation of 223 Ra-Labeled and Anti-PSMA Targeted NaA Nanozeolites for Prostate Cancer Therapy-Part II. Toxicity, Pharmacokinetics and Biodistribution.
- Author
-
Lankoff A, Czerwińska M, Walczak R, Karczmarczyk U, Tomczyk K, Brzóska K, Fracasso G, Garnuszek P, Mikołajczak R, and Kruszewski M
- Subjects
- Animals, Antibodies, Monoclonal, Apoptosis drug effects, Caspase 3 metabolism, Caspase 7 metabolism, Cell Line, Tumor, Chemical Phenomena, Chemistry Techniques, Synthetic, Disease Models, Animal, Drug Design, Gene Expression Profiling, Humans, Immunoconjugates administration & dosage, Immunoconjugates adverse effects, Isotope Labeling, Male, Mice, Mice, Nude, Molecular Structure, Prostatic Neoplasms diagnosis, Radiopharmaceuticals administration & dosage, Radiopharmaceuticals adverse effects, Radiopharmaceuticals chemistry, Tissue Distribution, Xenograft Model Antitumor Assays, Immunoconjugates pharmacokinetics, Nanoparticles chemistry, Prostatic Neoplasms therapy, Radiopharmaceuticals pharmacokinetics, Radium chemistry, Theranostic Nanomedicine, Zeolites chemistry
- Abstract
Metastatic castration-resistant prostate cancer (mCRPC) is a progressive and incurable disease with poor prognosis for patients. Despite introduction of novel therapies, the mortality rate remains high. An attractive alternative for extension of the life of mCRPC patients is PSMA-based targeted radioimmunotherapy. In this paper, we extended our in vitro study of
223 Ra-labeled and PSMA-targeted NaA nanozeolites [223 RaA-silane-PEG-D2B] by undertaking comprehensive preclinical in vitro and in vivo research. The toxicity of the new compound was evaluated in LNCaP C4-2, DU-145, RWPE-1 and HPrEC prostate cells and in BALB/c mice. The tissue distribution of133 Ba- and223 Ra-labeled conjugates was studied at different time points after injection in BALB/c and LNCaP C4-2 tumor-bearing BALB/c Nude mice. No obvious symptoms of antibody-free and antibody-functionalized nanocarriers cytotoxicity and immunotoxicity was found, while exposure to223 Ra-labeled conjugates resulted in bone marrow fibrosis, decreased the number of WBC and platelets and elevated serum concentrations of ALT and AST enzymes. Biodistribution studies revealed high accumulation of223 Ra-labeled conjugates in the liver, lungs, spleen and bone tissue. Nontargeted and PSMA-targeted radioconjugates exhibited a similar, marginal uptake in tumour lesions. In conclusion, despite the fact that NaA nanozeolites are safe carriers, the intravenous administration of NaA nanozeolite-based radioconjugates is dubious due to its high accumulation in the lungs, liver, spleen and bones.- Published
- 2021
- Full Text
- View/download PDF
40. Common Susceptibility Loci for Male Breast Cancer.
- Author
-
Maguire S, Perraki E, Tomczyk K, Jones ME, Fletcher O, Pugh M, Winter T, Thompson K, Cooke R, Trainer A, James P, Bojesen S, Flyger H, Nevanlinna H, Mattson J, Friedman E, Laitman Y, Palli D, Masala G, Zanna I, Ottini L, Silvestri V, Hollestelle A, Hooning MJ, Novaković S, Krajc M, Gago-Dominguez M, Castelao JE, Olsson H, Hedenfalk I, Saloustros E, Georgoulias V, Easton DF, Pharoah P, Dunning AM, Bishop DT, Neuhausen SL, Steele L, Ashworth A, Garcia Closas M, Houlston R, Swerdlow A, and Orr N
- Subjects
- Breast Neoplasms, Male chemistry, Case-Control Studies, Confidence Intervals, Female, Genome-Wide Association Study, Humans, Linear Models, Linkage Disequilibrium, Male, Odds Ratio, Receptors, Estrogen, Breast Neoplasms, Male genetics, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Quantitative Trait Loci
- Abstract
Background: The etiology of male breast cancer (MBC) is poorly understood. In particular, the extent to which the genetic basis of MBC differs from female breast cancer (FBC) is unknown. A previous genome-wide association study of MBC identified 2 predisposition loci for the disease, both of which were also associated with risk of FBC., Methods: We performed genome-wide single nucleotide polymorphism genotyping of European ancestry MBC case subjects and controls in 3 stages. Associations between directly genotyped and imputed single nucleotide polymorphisms with MBC were assessed using fixed-effects meta-analysis of 1380 cases and 3620 controls. Replication genotyping of 810 cases and 1026 controls was used to validate variants with P values less than 1 × 10-06. Genetic correlation with FBC was evaluated using linkage disequilibrium score regression, by comprehensively examining the associations of published FBC risk loci with risk of MBC and by assessing associations between a FBC polygenic risk score and MBC. All statistical tests were 2-sided., Results: The genome-wide association study identified 3 novel MBC susceptibility loci that attained genome-wide statistical significance (P < 5 × 10-08). Genetic correlation analysis revealed a strong shared genetic basis with estrogen receptor-positive FBC. Men in the top quintile of genetic risk had a fourfold increased risk of breast cancer relative to those in the bottom quintile (odds ratio = 3.86, 95% confidence interval = 3.07 to 4.87, P = 2.08 × 10-30)., Conclusions: These findings advance our understanding of the genetic basis of MBC, providing support for an overlapping genetic etiology with FBC and identifying a fourfold high-risk group of susceptible men., (© The Author(s) 2020. Published by Oxford University Press.)
- Published
- 2021
- Full Text
- View/download PDF
41. CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers.
- Author
-
Johnson N, Maguire S, Morra A, Kapoor PM, Tomczyk K, Jones ME, Schoemaker MJ, Gilham C, Bolla MK, Wang Q, Dennis J, Ahearn TU, Andrulis IL, Anton-Culver H, Antonenkova NN, Arndt V, Aronson KJ, Augustinsson A, Baynes C, Freeman LEB, Beckmann MW, Benitez J, Bermisheva M, Blomqvist C, Boeckx B, Bogdanova NV, Bojesen SE, Brauch H, Brenner H, Burwinkel B, Campa D, Canzian F, Castelao JE, Chanock SJ, Chenevix-Trench G, Clarke CL, Conroy DM, Couch FJ, Cox A, Cross SS, Czene K, Dörk T, Eliassen AH, Engel C, Evans DG, Fasching PA, Figueroa J, Floris G, Flyger H, Gago-Dominguez M, Gapstur SM, García-Closas M, Gaudet MM, Giles GG, Goldberg MS, González-Neira A, Guénel P, Hahnen E, Haiman CA, Håkansson N, Hall P, Hamann U, Harrington PA, Hart SN, Hooning MJ, Hopper JL, Howell A, Hunter DJ, Jager A, Jakubowska A, John EM, Kaaks R, Keeman R, Khusnutdinova E, Kitahara CM, Kosma VM, Koutros S, Kraft P, Kristensen VN, Kurian AW, Lambrechts D, Le Marchand L, Linet M, Lubiński J, Mannermaa A, Manoukian S, Margolin S, Martens JWM, Mavroudis D, Mayes R, Meindl A, Milne RL, Neuhausen SL, Nevanlinna H, Newman WG, Nielsen SF, Nordestgaard BG, Obi N, Olshan AF, Olson JE, Olsson H, Orban E, Park-Simon TW, Peterlongo P, Plaseska-Karanfilska D, Pylkäs K, Rennert G, Rennert HS, Ruddy KJ, Saloustros E, Sandler DP, Sawyer EJ, Schmutzler RK, Scott C, Shu XO, Simard J, Smichkoska S, Sohn C, Southey MC, Spinelli JJ, Stone J, Tamimi RM, Taylor JA, Tollenaar RAEM, Tomlinson I, Troester MA, Truong T, Vachon CM, van Veen EM, Wang SS, Weinberg CR, Wendt C, Wildiers H, Winqvist R, Wolk A, Zheng W, Ziogas A, Dunning AM, Pharoah PDP, Easton DF, Howie AF, Peto J, Dos-Santos-Silva I, Swerdlow AJ, Chang-Claude J, Schmidt MK, Orr N, and Fletcher O
- Subjects
- Alleles, Breast Neoplasms enzymology, Breast Neoplasms urine, Case-Control Studies, Cytochrome P-450 CYP3A metabolism, Estrone genetics, Estrone urine, Female, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Pregnanediol genetics, Pregnanediol urine, Premenopause, Breast Neoplasms genetics, Cytochrome P-450 CYP3A genetics, Estrone analogs & derivatives, Pregnanediol analogs & derivatives, Progesterone urine, Receptors, Estrogen metabolism, Receptors, Progesterone metabolism
- Abstract
Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk., Methods: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry., Results: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 × 10
-18 ); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 × 10-8 )., Conclusions: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.- Published
- 2021
- Full Text
- View/download PDF
42. HEALTH RISK RELATED TO EXPOSURE TO TOXIC COMPOUNDS CONTAINED IN MINERAL AND SPRING WATERS.
- Author
-
Tomczyk K, Dziubanek G, Kowalska A, Szymala I, and Łabuz-Roszak B
- Subjects
- Humans, Minerals, Arsenic analysis, Arsenic toxicity, Drinking Water, Mercury, Mineral Waters
- Abstract
Objective: The aim: The study aimed to assess the content of selected toxic compounds in mineral and spring waters available on the Polish market regarding potential health risks to consumers., Patients and Methods: Materials and methods: Selected mineral and spring waters available on the Polish market were the study's objects. The content of such chemical compounds as arsenic, cadmium, lead, copper, and mercury in selected mineral and spring waters was analyzed. The content of metals in the samples was determined by inductively coupled plasma mass spectrometry (ICP-MS). Additionally, a literature review was performed to determine nitrates contamination of bottled waters available on the Polish market. Based on the collected data, an assessment of exposure and health risk to consumers was performed., Results: Results: Arsenic had the highest mean concentration in the analyzed water samples. Consumption of such contaminated waters may be a significant health risk factor for consumers. Literature data indicate a relatively low content of nitrates in bottled waters available on the Polish market. Consumption of such mineral waters is not a significant source of exposure and does not translate into a significant health risk for consumers., Conclusion: Conclusions: To ensure consumers' health safety, there is a need to monitor the content of potentially harmful compounds in mineral and spring waters available on the Polish market.
- Published
- 2021
43. KNOWLEDGE AND ATTITUDES OF YOUNG PEOPLE IN THE FIELD OF EATING DISORDERS.
- Author
-
Zdanek A, Łabuz-Roszak B, Szlacheta P, Tomczyk K, Wąsek K, Roszak M, and Korzonek-Szlacheta I
- Subjects
- Adolescent, Attitude, Body Weight, Female, Humans, Male, Students, Surveys and Questionnaires, Feeding and Eating Disorders
- Abstract
Objective: The aim: To examine the level of knowledge and attitudes of high school students in the field of eating disorders., Patients and Methods: Materials and methods: The study group consisted of students of a randomly selected village school (Jendrzejow) and the municipal school (Siemianowice Slaskie). The study was conducted using an original survey consisting of 10 questions regarding the knowledge and attitudes of respondents towards eating disorders., Results: Results: A total of 313 students (242 female and 71 male) participated in the study. 44.7% of respondents from the village school and 56.6% of respondents from the municipal school were dissatisfied with their appearance; 21.6% and 27.9%, respectively, were currently using the diet. 68% of students from Jędrzejow and 53.3% of students from Siemianowice Slaskie made an attempt to reduce body weight at least once in their lives. 55.1% of the village school respondents and 47.4% of the municipal school respondents noticed the influence of the media on the desire to achieve a slim figure. Girls showed better knowledge about eating disorders than boys (p = 0.008). Over 70% of students of both surveyed high schools believed that people with eating disorders are unable to cope with the disease on their own. Only 6.7% of students of the municipal school and 12.92% of students of the village school gave themselves a very good grade., Conclusion: Conclusions: There is a need to educate young people more broadly about eating disorders and the risk factors for their occurrence.
- Published
- 2021
44. Procedure for Determining the Uncertainties in the Modeling of Surface Roughness in the Turning of NiTi Alloys Using the Monte Carlo Method.
- Author
-
Kowalczyk M and Tomczyk K
- Abstract
The paper presents a procedure for the determination of uncertainties in the modeling of surface roughness in the turning of NiTi alloys. The presented procedure is applicable both to the analysis of the measurement values of the two main roughness factors, as well as to research related to the prediction and optimization of the machining process. Type A and B, total, and expanded uncertainties were considered herein, and the obtained uncertainty values were assessed. A procedure for optimizing machining by applying the Monte Carlo (MC) method is also presented. The solutions presented in this paper are important from the point of view of practical solutions related to the prediction and optimization of the machining process. The considered procedure for determining and assessing uncertainty can be useful for the optimal selection of both machining parameters and measuring tools., Competing Interests: The authors declare no conflict of interest.
- Published
- 2020
- Full Text
- View/download PDF
45. DNA methylation of the long intergenic noncoding RNA 299 gene in triple-negative breast cancer: results from a prospective study.
- Author
-
Manoochehri M, Jones M, Tomczyk K, Fletcher O, Schoemaker MJ, Swerdlow AJ, Borhani N, and Hamann U
- Subjects
- Adult, Age of Onset, Aged, Aged, 80 and over, Biomarkers, Tumor, Cell Line, Tumor, Female, Gene Expression Profiling, Genetic Heterogeneity, Humans, Middle Aged, Odds Ratio, Triple Negative Breast Neoplasms metabolism, Triple Negative Breast Neoplasms pathology, DNA Methylation, Gene Expression Regulation, Neoplastic, RNA, Long Noncoding genetics, Triple Negative Breast Neoplasms genetics
- Abstract
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with a high rate of recurrence and poor prognosis. Recently we identified a hypermethylation in the long noncoding RNA 299 (LINC00299) gene in blood-derived DNA from TNBC patients compared with healthy controls implying that LINC00299 hypermethylation may serve as a circulating biomarker for TNBC. In the present study, we investigated whether LINC00299 methylation is associated with TNBC in a prospective nested breast cancer case-control study within the Generations Study. Methylation at cg06588802 in LINC00299 was measured in 154 TNBC cases and 159 breast cancer-free matched controls using MethyLight droplet digital PCR. To assess the association between methylation level and TNBC risk, logistic regression was used to calculate odd ratios and 95% confidence intervals, adjusted for smoking status. We found no evidence for association between methylation levels and TNBC overall (P = 0.062). Subgroup analysis according to age at diagnosis and age at blood draw revealed increased methylation levels in TNBC cases compared with controls in the young age groups [age 26-52 (P = 0.0025) and age 22-46 (P = 0.001), respectively]. Our results suggest a potential association of LINC00299 hypermethylation with TNBC in young women.
- Published
- 2020
- Full Text
- View/download PDF
46. ASSESSMENT OF ADULT EATING HABITS IN THE NUTRITIONAL PREVENTION OF STROKE.
- Author
-
Sobalska A, Tomczyk K, Furman J, and Łabuz-Roszak B
- Subjects
- Adult, Aged, Aged, 80 and over, Diet, Female, Humans, Male, Middle Aged, Poland, Surveys and Questionnaires, Vegetables, Feeding Behavior, Stroke prevention & control
- Abstract
Objective: Introduction: Lifestyle modification, including changing eating habits, plays an essential role in the prevention of stroke. The aim: The study aimed to assess the nutritional prevention of cerebrovascular diseases in adult inhabitants of Poland., Patients and Methods: Material and Methods: The study was conducted using the author's questionnaire among 145 women and 76 men, aged 18 - 30 (53.9%) and 50 - 70 (46.1%) years., Results: Results: The following stroke risk factors were found in the examined group: overweight or obesity (46.6%), lack of regular physical activity (48%), smoking (33%), hypertension (22.1%), dyslipidemia (8.6%), diabetes (5.9%), and cardiac arrhythmias (6.3%). The younger subjects compared to older ones more often declared the daily consumption of whole-grain cereal products and vegetables, fish at least once a week, and they preferred vegetable oils. On the other hand, older subjects declared the consumption of sweets, sweet drinks, salt, and fast food less frequently than younger ones. Also, fruits were more often chosen by older people. Both groups declared similar moderate consumption of milk and dairy products with reduced fat content, lean meat, and alcohol. Only 38% of respondents considered their eating habits to be appropriate., Conclusion: Conclusions: The eating habits of examined adults only partially met the recommendations regarding the nutritional prevention of stroke. In some elements, younger people were more likely to follow appropriate dietary recommendations, while older people were more appropriate in others. The education regarding the principles of the nutritional prevention of cerebrovascular diseases is still necessary and should be age-appropriate.
- Published
- 2020
47. ASSOCIATION BETWEEN EATING HABITS AND PHYSICAL ACTIVITY IN PRIMARY SCHOOL STUDENTS.
- Author
-
Kiebuła P, Tomczyk K, Furman J, and Łabuz-Roszak B
- Subjects
- Child, Cross-Sectional Studies, Exercise, Female, Humans, Male, Poland, Schools, Surveys and Questionnaires, Feeding Behavior, Students
- Abstract
Objective: The aim: The study aimed to assess the association between the physical activity level and eating habits of primary school students., Patients and Methods: Material and methods: 139 children attending one of the Polish primary school or football school were included. The research tool was author's anonymous survey., Results: Results: The high physical activity level was observed in 34.1% of boys and in 8.8% of girls. As the level of physical activity increased, the consumption of vegetables and fruits also increased. Whole grain bread, coarse-grained groats, whole grain pasta and brown rice were more popular among students with a high physical activity level. The greater the physical activity, the greater the amount of water drank by students. The consumption of sweets, fast food, and ready-made meals, such as frozen pizza or Chinese soup, decreased with increased physical activity. The choice of healthier substitutes for unhealthy snacks was declared by students with moderate or high physical activity level. There was no correlation between BMI and age and the physical activity level. Girls were less active than boys., Conclusion: Conclusions: More active physically children had better eating habits and were more aware of healthy eating principles than less active people.
- Published
- 2020
48. Radial Basis Functions Intended to Determine the Upper Bound of Absolute Dynamic Error at the Output of Voltage-Mode Accelerometers.
- Author
-
Tomczyk K, Piekarczyk M, and Sokal G
- Abstract
In this paper, we propose using the radial basis functions ( RBF ) to determine the upper bound of absolute dynamic error ( UAE ) at the output of a voltage-mode accelerometer. Such functions can be obtained as a result of approximating the error values determined for the assumed-in-advance parameter variability associated with the mathematical model of an accelerometer. This approximation was carried out using the radial basis function neural network ( RBF-NN ) procedure for a given number of the radial neurons. The Monte Carlo (MC) method was also applied to determine the related error when considering the uncertainties associated with the parameters of an accelerometer mathematical model. The upper bound of absolute dynamic error can be a quality ratio for comparing the errors produced by different types of voltage-mode accelerometers that have the same operational frequency bandwidth. Determination of the RBFs was performed by applying the Python-related scientific packages, while the calculations related both to the UAE and the MC method were carried out using the MathCad program. Application of the RBFs represent a new approach for determining the UAE . These functions allow for the easy and quick determination of the value of such errors.
- Published
- 2019
- Full Text
- View/download PDF
49. Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk.
- Author
-
Johansson A, Palli D, Masala G, Grioni S, Agnoli C, Tumino R, Giurdanella MC, Fasanelli F, Sacerdote C, Panico S, Mattiello A, Polidoro S, Jones ME, Schoemaker MJ, Orr N, Tomczyk K, Johnson N, Fletcher O, Perduca V, Baglietto L, Dugué PA, Southey MC, Giles GG, English DR, Milne RL, Severi G, Ambatipudi S, Cuenin C, Chajès V, Romieu I, Herceg Z, Swerdlow AJ, Vineis P, and Flanagan JM
- Subjects
- Case-Control Studies, CpG Islands, Epigenesis, Genetic, Female, Genetic Predisposition to Disease, Humans, Italy, Middle Aged, Prospective Studies, Breast Neoplasms genetics, DNA Methylation drug effects, Estrogens adverse effects, Genome-Wide Association Study methods
- Abstract
Background: It is well established that estrogens and other hormonal factors influence breast cancer susceptibility. We hypothesized that a woman's total lifetime estrogen exposure accumulates changes in DNA methylation, detectable in the blood, which could be used in risk assessment for breast cancer., Methods: An estimated lifetime estrogen exposure (ELEE) model was defined using epidemiological data from EPIC-Italy (n = 31,864). An epigenome-wide association study (EWAS) of ELEE was performed using existing Illumina HumanMethylation450K Beadchip (HM450K) methylation data obtained from EPIC-Italy blood DNA samples (n = 216). A methylation index (MI) of ELEE based on 31 CpG sites was developed using HM450K data from EPIC-Italy and the Generations Study and evaluated for association with breast cancer risk in an independent dataset from the Generations Study (n = 440 incident breast cancer cases matched to 440 healthy controls) using targeted bisulfite sequencing. Lastly, a meta-analysis was conducted including three additional cohorts, consisting of 1187 case-control pairs., Results: We observed an estimated 5% increase in breast cancer risk per 1-year longer ELEE (OR = 1.05, 95% CI 1.04-1.07, P = 3 × 10
-12 ) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data (ORQ4_vs_Q1 = 1.77, 95% CI 1.07-2.93, P = 0.027) and in the meta-analysis (ORQ4_vs_Q1 = 1.43, 95% CI 1.05-2.00, P = 0.024); however, the correlation between the MI and ELEE was not validated across study cohorts., Conclusion: We have identified a blood DNA methylation signature associated with breast cancer risk in this study. Further investigation is required to confirm the interaction between estrogen exposure and DNA methylation in the blood.- Published
- 2019
- Full Text
- View/download PDF
50. [Nutrition in selected old age diseases].
- Author
-
Mituła M, Tomczyk K, and Łabuz-Roszak B
- Subjects
- Diet, Europe, Humans, Nutritional Status, Poland, Diabetes Mellitus, Type 2
- Abstract
In the population of Poland, as well as in other European countries, an aging process is taking place. It is expected that in Poland in 2050, up to 35% of the population may be seniors. With increasing age, there are numerous changes in the body that necessitate the modification of the current diet. Incorrect diet is a risk factor for many old age diseases, including neurodegenerative diseases, osteoporosis, atherosclerosis, stroke, type 2 diabetes and hypertension. The aim of this study is to review the nutrition recommendations in selected diseases of the elderly. The diet of seniors should provide the right amount of nutrients and be adapted to existing diseases. A proper diet can reduce the risk of complications from senile diseases.
- Published
- 2019
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.