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13 results on '"Dörk, Thilo"'

1. Germline copy number variants and endometrial cancer risk

Author

Stylianou, Cassie E., Wiggins, George A. R., Lau, Vanessa L., Dennis, Joe, Shelling, Andrew N., Wilson, Michelle, Sykes, Peter, Amant, Frederic, Annibali, Daniela, De Wispelaere, Wout, Easton, Douglas F., Fasching, Peter A., Glubb, Dylan M., Goode, Ellen L., Lambrechts, Diether, Pharoah, Paul D. P., Scott, Rodney J., Tham, Emma, Tomlinson, Ian, Bolla, Manjeet K., Couch, Fergus J., Czene, Kamila, Dörk, Thilo, Dunning, Alison M., Fletcher, Olivia, García-Closas, Montserrat, Hoppe, Reiner, Jernström, Helena, Kaaks, Rudolf, Michailidou, Kyriaki, Obi, Nadia, Southey, Melissa C., Stone, Jennifer, Wang, Qin, Spurdle, Amanda B., O’Mara, Tracy A., Pearson, John, and Walker, Logan C.

Published
2024
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2. Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

Author

Cuellar-Partida, Gabriel, Lu, Yi, Dixon, Suzanne C, Australian Ovarian Cancer Study, Fasching, Peter A, Hein, Alexander, Burghaus, Stefanie, Beckmann, Matthias W, Lambrechts, Diether, Van Nieuwenhuysen, Els, Vergote, Ignace, Vanderstichele, Adriaan, Doherty, Jennifer Anne, Rossing, Mary Anne, Chang-Claude, Jenny, Rudolph, Anja, Wang-Gohrke, Shan, Goodman, Marc T, Bogdanova, Natalia, Dörk, Thilo, Dürst, Matthias, Hillemanns, Peter, Runnebaum, Ingo B, Antonenkova, Natalia, Butzow, Ralf, Leminen, Arto, Nevanlinna, Heli, Pelttari, Liisa M, Edwards, Robert P, Kelley, Joseph L, Modugno, Francesmary, Moysich, Kirsten B, Ness, Roberta B, Cannioto, Rikki, Høgdall, Estrid, Høgdall, Claus, Jensen, Allan, Giles, Graham G, Bruinsma, Fiona, Kjaer, Susanne K, Hildebrandt, Michelle AT, Liang, Dong, Lu, Karen H, Wu, Xifeng, Bisogna, Maria, Dao, Fanny, Levine, Douglas A, Cramer, Daniel W, Terry, Kathryn L, Tworoger, Shelley S, Stampfer, Meir, Missmer, Stacey, Bjorge, Line, Salvesen, Helga B, Kopperud, Reidun K, Bischof, Katharina, Aben, Katja KH, Kiemeney, Lambertus A, Massuger, Leon FAG, Brooks-Wilson, Angela, Olson, Sara H, McGuire, Valerie, Rothstein, Joseph H, Sieh, Weiva, Whittemore, Alice S, Cook, Linda S, Le, Nhu D, Blake Gilks, C, Gronwald, Jacek, Jakubowska, Anna, Lubiński, Jan, Kluz, Tomasz, Song, Honglin, Tyrer, Jonathan P, Wentzensen, Nicolas, Brinton, Louise, Trabert, Britton, Lissowska, Jolanta, McLaughlin, John R, Narod, Steven A, Phelan, Catherine, Anton-Culver, Hoda, Ziogas, Argyrios, Eccles, Diana, Campbell, Ian, Gayther, Simon A, Gentry-Maharaj, Aleksandra, Menon, Usha, Ramus, Susan J, Wu, Anna H, Dansonka-Mieszkowska, Agnieszka, Kupryjanczyk, Jolanta, Timorek, Agnieszka, Szafron, Lukasz, Cunningham, Julie M, Fridley, Brooke L, Winham, Stacey J, Bandera, Elisa V, Poole, Elizabeth M, and Morgan, Terry K

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Obesity, Women's Health, Cancer Genomics, Ovarian Cancer, Cancer, Human Genome, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Carcinoma, Ovarian Epithelial, Female, Genotype, Humans, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Pathology, Molecular, Polymorphism, Single Nucleotide, Australian Ovarian Cancer Study, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity, Reproductive medicine
Abstract

Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ([Formula: see text] = 8.8 ± 1.1 %), endometrioid ([Formula: see text] = 3.2 ± 1.6 %), clear cell ([Formula: see text] = 6.7 ± 3.3 %) and all EOC ([Formula: see text] = 5.6 ± 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach.

Published
2016

3. Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium

Author

Lei, Jieping, Rudolph, Anja, Moysich, Kirsten B, Behrens, Sabine, Goode, Ellen L, Bolla, Manjeet K, Dennis, Joe, Dunning, Alison M, Easton, Douglas F, Wang, Qin, Benitez, Javier, Hopper, John L, Southey, Melissa C, Schmidt, Marjanka K, Broeks, Annegien, Fasching, Peter A, Haeberle, Lothar, Peto, Julian, dos-Santos-Silva, Isabel, Sawyer, Elinor J, Tomlinson, Ian, Burwinkel, Barbara, Marmé, Frederik, Guénel, Pascal, Truong, Thérèse, Bojesen, Stig E, Flyger, Henrik, Nielsen, Sune F, Nordestgaard, Børge G, González-Neira, Anna, Menéndez, Primitiva, Anton-Culver, Hoda, Neuhausen, Susan L, Brenner, Hermann, Arndt, Volker, Meindl, Alfons, Schmutzler, Rita K, Brauch, Hiltrud, Hamann, Ute, Nevanlinna, Heli, Fagerholm, Rainer, Dörk, Thilo, Bogdanova, Natalia V, Mannermaa, Arto, Hartikainen, Jaana M, Australian Ovarian Study Group, kConFab Investigators, Van Dijck, Laurien, Smeets, Ann, Flesch-Janys, Dieter, Eilber, Ursula, Radice, Paolo, Peterlongo, Paolo, Couch, Fergus J, Hallberg, Emily, Giles, Graham G, Milne, Roger L, Haiman, Christopher A, Schumacher, Fredrick, Simard, Jacques, Goldberg, Mark S, Kristensen, Vessela, Borresen-Dale, Anne-Lise, Zheng, Wei, Beeghly-Fadiel, Alicia, Winqvist, Robert, Grip, Mervi, Andrulis, Irene L, Glendon, Gord, García-Closas, Montserrat, Figueroa, Jonine, Czene, Kamila, Brand, Judith S, Darabi, Hatef, Eriksson, Mikael, Hall, Per, Li, Jingmei, Cox, Angela, Cross, Simon S, Pharoah, Paul DP, Shah, Mitul, Kabisch, Maria, Torres, Diana, Jakubowska, Anna, Lubinski, Jan, Ademuyiwa, Foluso, Ambrosone, Christine B, Swerdlow, Anthony, Jones, Michael, and Chang-Claude, Jenny

Subjects
Breast Cancer, Genetics, Human Genome, Cancer, 2.1 Biological and endogenous factors, Aetiology, Breast Neoplasms, Case-Control Studies, Female, Genetic Predisposition to Disease, Humans, Immune Tolerance, Polymorphism, Single Nucleotide, Australian Ovarian Study Group, kConFab Investigators, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity
Abstract

Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113 matched normal tissue samples. SNP rs1905339 (A>G) in the STAT3 region was associated with an increased breast cancer risk (per allele odds ratio 1.05, 95 % confidence interval 1.03-1.08; p value = 1.4 × 10(-6)). The association did not differ significantly by ER status. On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 × 10(-3) and 7.0 × 10(-3), respectively). Furthermore, STAT3 and IL5 but not GM-CSF were differentially expressed between breast tumor tissue and normal tissue (p value = 2.5 × 10(-3), 4.5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry.

Published
2016

4. Candidate locus analysis of the TERT–CLPTM1L cancer risk region on chromosome 5p15 identifies multiple independent variants associated with endometrial cancer risk

Author

Carvajal-Carmona, Luis G, O’Mara, Tracy A, Painter, Jodie N, Lose, Felicity A, Dennis, Joe, Michailidou, Kyriaki, Tyrer, Jonathan P, Ahmed, Shahana, Ferguson, Kaltin, Healey, Catherine S, Pooley, Karen, Beesley, Jonathan, Cheng, Timothy, Jones, Angela, Howarth, Kimberley, Martin, Lynn, Gorman, Maggie, Hodgson, Shirley, National Study of Endometrial Cancer Genetics Group (NSECG), The Australian National Endometrial Cancer Study Group (ANECS), Wentzensen, Nicholas, Fasching, Peter A, Hein, Alexander, Beckmann, Matthias W, Renner, Stefan P, Dörk, Thilo, Hillemanns, Peter, Dürst, Matthias, Runnebaum, Ingo, Lambrechts, Diether, Coenegrachts, Lieve, Schrauwen, Stefanie, Amant, Frederic, Winterhoff, Boris, Dowdy, Sean C, Goode, Ellen L, Teoman, Attila, Salvesen, Helga B, Trovik, Jone, Njolstad, Tormund S, Werner, Henrica MJ, Scott, Rodney J, Ashton, Katie, Proietto, Tony, Otton, Geoffrey, Wersäll, Ofra, Mints, Miriam, Tham, Emma, RENDOCAS, Hall, Per, Czene, Kamila, Liu, Jianjun, Li, Jingmei, Hopper, John L, Southey, Melissa C, Australian Ovarian Cancer Study (AOCS), Ekici, Arif B, Ruebner, Matthias, Johnson, Nichola, Peto, Julian, Burwinkel, Barbara, Marme, Frederik, Brenner, Hermann, Dieffenbach, Aida K, Meindl, Alfons, Brauch, Hiltrud, The GENICA Network, Lindblom, Annika, Depreeuw, Jeroen, Moisse, Matthieu, Chang-Claude, Jenny, Rudolph, Anja, Couch, Fergus J, Olson, Janet E, Giles, Graham G, Bruinsma, Fiona, Cunningham, Julie M, Fridley, Brooke L, Børresen-Dale, Anne-Lise, Kristensen, Vessela N, Cox, Angela, Swerdlow, Anthony J, Orr, Nicholas, Bolla, Manjeet K, Wang, Qin, Weber, Rachel Palmieri, Chen, Zhihua, Shah, Mitul, Pharoah, Paul DP, Dunning, Alison M, Tomlinson, Ian, Easton, Douglas F, Spurdle, Amanda B, and Thompson, Deborah J

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Genetic Testing, Human Genome, Prevention, Cancer, Uterine Cancer, 2.1 Biological and endogenous factors, Aetiology, Chromosomes, Human, Pair 5, Databases, Nucleic Acid, Female, Gene Expression Regulation, Neoplastic, Genetic Loci, Haplotypes, Humans, Membrane Proteins, Models, Genetic, Neoplasm Proteins, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Risk Factors, Telomerase, National Study of Endometrial Cancer Genetics Group, Australian National Endometrial Cancer Study Group, RENDOCAS, Australian Ovarian Cancer Study, GENICA Network, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity, Reproductive medicine
Abstract

Several studies have reported associations between multiple cancer types and single-nucleotide polymorphisms (SNPs) on chromosome 5p15, which harbours TERT and CLPTM1L, but no such association has been reported with endometrial cancer. To evaluate the role of genetic variants at the TERT-CLPTM1L region in endometrial cancer risk, we carried out comprehensive fine-mapping analyses of genotyped and imputed SNPs using a custom Illumina iSelect array which includes dense SNP coverage of this region. We examined 396 SNPs (113 genotyped, 283 imputed) in 4,401 endometrial cancer cases and 28,758 controls. Single-SNP and forward/backward logistic regression models suggested evidence for three variants independently associated with endometrial cancer risk (P = 4.9 × 10(-6) to P = 7.7 × 10(-5)). Only one falls into a haplotype previously associated with other cancer types (rs7705526, in TERT intron 1), and this SNP has been shown to alter TERT promoter activity. One of the novel associations (rs13174814) maps to a second region in the TERT promoter and the other (rs62329728) is in the promoter region of CLPTM1L; neither are correlated with previously reported cancer-associated SNPs. Using TCGA RNASeq data, we found significantly increased expression of both TERT and CLPTM1L in endometrial cancer tissue compared with normal tissue (TERT P = 1.5 × 10(-18), CLPTM1L P = 1.5 × 10(-19)). Our study thus reports a novel endometrial cancer risk locus and expands the spectrum of cancer types associated with genetic variation at 5p15, further highlighting the importance of this region for cancer susceptibility.

Published
2015

5. Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA

Author

Earp, Madalene A, Kelemen, Linda E, Magliocco, Anthony M, Swenerton, Kenneth D, Chenevix-Trench, Georgia, Australian Cancer Study, Australian Ovarian Cancer Study Group, Lu, Yi, Hein, Alexander, Ekici, Arif B, Beckmann, Matthias W, Fasching, Peter A, Lambrechts, Diether, Despierre, Evelyn, Vergote, Ignace, Lambrechts, Sandrina, Doherty, Jennifer A, Rossing, Mary Anne, Chang-Claude, Jenny, Rudolph, Anja, Friel, Grace, Moysich, Kirsten B, Odunsi, Kunle, Sucheston-Campbell, Lara, Lurie, Galina, Goodman, Marc T, Carney, Michael E, Thompson, Pamela J, Runnebaum, Ingo B, Dürst, Matthias, Hillemanns, Peter, Dörk, Thilo, Antonenkova, Natalia, Bogdanova, Natalia, Leminen, Arto, Nevanlinna, Heli, Pelttari, Liisa M, Butzow, Ralf, Bunker, Clareann H, Modugno, Francesmary, Edwards, Robert P, Ness, Roberta B, du Bois, Andreas, Heitz, Florian, Schwaab, Ira, Harter, Philipp, Karlan, Beth Y, Walsh, Christine, Lester, Jenny, Jensen, Allan, Kjær, Susanne K, Høgdall, Claus K, Høgdall, Estrid, Lundvall, Lene, Sellers, Thomas A, Fridley, Brooke L, Goode, Ellen L, Cunningham, Julie M, Vierkant, Robert A, Giles, Graham G, Baglietto, Laura, Severi, Gianluca, Southey, Melissa C, Liang, Dong, Wu, Xifeng, Lu, Karen, Hildebrandt, Michelle AT, Levine, Douglas A, Bisogna, Maria, Schildkraut, Joellen M, Iversen, Edwin S, Weber, Rachel Palmieri, Berchuck, Andrew, Cramer, Daniel W, Terry, Kathryn L, Poole, Elizabeth M, Tworoger, Shelley S, Bandera, Elisa V, Chandran, Urmila, Orlow, Irene, Olson, Sara H, Wik, Elisabeth, Salvesen, Helga B, Bjorge, Line, Halle, Mari K, van Altena, Anne M, Aben, Katja KH, Kiemeney, Lambertus A, Massuger, Leon FAG, Pejovic, Tanja, Bean, Yukie T, Cybulski, Cezary, Gronwald, Jacek, Lubinski, Jan, Wentzensen, Nicolas, Brinton, Louise A, Lissowska, Jolanta, Garcia-Closas, Montserrat, Dicks, Ed, and Dennis, Joe

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Rare Diseases, Prevention, Ovarian Cancer, Human Genome, Cancer, 2.1 Biological and endogenous factors, Aetiology, Alleles, Carcinoma, Ovarian Epithelial, DNA, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Quality Control, Australian Cancer Study, Australian Ovarian Cancer Study Group, Ovarian Cancer Association Consortium, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity, Reproductive medicine
Abstract

Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS [56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low-malignant potential (LMP) serous, and 24 for invasive serous EOC], selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95 % confidence intervals are reported. Nine variants tagging six loci were associated with subtype-specific EOC risk at P

Published
2014

13. Characterization of a novel 21-kb deletion, CFTRdele2,3(21 kb), in the CFTR gene: a cystic fibrosis mutation of Slavic origin common in Central and East Europe.

Author

Dörk, Thilo, Macek Jr., Milan, Mekus, Frauke, Tümmler, Burkhard, Tzountzouris, John, Casals, Teresa, Krebsová, Alice, Koudová, Monika, Sakmaryová, Iva, Macek Sr., Milan, Vávrová, Vecaron;ra, Zemková, Dana, Ginter, Evgeny, Petrova, Nica V., Ivaschenko, Tatiana, Baranov, Vladislav, Witt, Michal, Pogorzelski, Andrzej, Bal, Jerzy, and Zékanowsky, Cesary

Subjects
CYSTIC fibrosis, GENETIC disorders, MOLECULAR genetics, MEDICAL genetics, HUMAN genetics, HUMAN biology, GENETICS
Abstract

We report a large genomic deletion of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, viz., a deletion that is frequently observed in Central and Eastern Europe. The mutation, termed CFTRdele2,3(21 kb), deletes 21,080 bp spanning introns 1–3 of the CFTR gene. Transcript analyses have revealed that this deletion results in the loss of exons 2 and 3 in epithelial CFTR mRNA, thereby producing a premature termination signal within exon 4. In order to develop a simple polymerase chain reaction assay for this allele, we defined the end-points of the deletion at the DNA sequence level. We next screened for this mutation in a representative set of European and European-derived populations. Some 197 CF patients, including seven homozygotes, bearing this mutation have been identified during the course of our study. Clinical evaluation of CFTRdele2,3(21 kb) homozygotes and a comparison of compound heterozygotes for ΔF508/CFTRdele2,3(21 kb) with pairwise-matched ΔF508 homozygotes indicate that this deletion represents a severe mutation associated with pancreatic insufficiency and early age at diagnosis. Current data show that the mutation is particularly common in Czech (6.4% of all CF chromosomes), Russian (5.2%), Belorussian (3.3%), Austrian (2.6%), German (1.5%), Polish (1.5%), Slovenian (1.5%), Ukrainian (1.2%), and Slovak patients (1.1%). It has also been found in Lithuania, Latvia, Macedonia and Greece and has sporadically been observed in Canada, USA, France, Spain, Turkey, and UK, but not in CF patients from Bulgaria, Croatia, Romania or Serbia. Haplotype analysis has identified the same extragenic CF-haplotype XV-2c/KM.19 "A" and the same infrequent intragenic microsatellite haplotype 16–33–13 (IVS8CA-IVS17bTA-IVS17bCA) in all examined CFTRdele2,3(21 kb) chromosomes, suggesting a common origin for this deletion. We conclude that the 21-kb deletion is a frequent and severe CF mutation in populations of Eastern- and Western-Slavic descent. [ABSTRACT FROM AUTHOR]

Published
2000
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