33 results on '"Toloczko-Grabarek A"'
Search Results
2. Nuclear Pedigree Criteria for the Identification of Individuals Suspected to be at Risk of an Inherited Predisposition to Renal Cancer
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Tołoczko-Grabarek Aleksandra, Sikorski Andrzej, Brzosko Marek, and Lubiński Jan
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hereditary clear cell renal cancer ,diagnostic criteria ,nuclear families ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Abstract
Abstract Renal clear cell carcinomas represent about 3% of all visceral cancers and account for approximately 85% of renal cancers in adults. Environmental and genetic factors are involved in the development of renal cancer. Although to date there are 19 hereditary syndromes described in which renal cell cancer may occur, only four syndromes with an unequivocal genetic predisposition to renal cell carcinoma have been identified: VHL syndrome (mutations in the VHL gene), hereditary clear cell carcinoma (translocations t(3:8), t(2:3)), hereditary papillary carcinoma (mutations in the MET protooncogene) and tuberous sclerosis (mutations in the TSC1 and TSC2 genes). Little is known genetically about the other forms of familial renal cell cancer. Since there is a growing awareness about the necessity of early intervention, clinical criteria have been developed that aid in the identification of hereditary forms of renal cancer. The aim of the current study was to identify minimal inclusion criteria so that nuclear pedigree families can be ascertained for risk assessment and/or kidney tumour screening. The results reveal that inclusion features described herein, such as (a) renal clear cell cancer diagnosed before 55 years of age, and (b) renal clear cell cancer and gastric cancer or lung cancer among first degree relatives, are useful in identifying suspected hereditary clear cell renal cancer patients.
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- 2005
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3. Iron and breast cancer risk
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Sukiennicki Grzegorz, Muszyńska Magdalena, Huzarski Tomasz, Gronwald Jacek, Cybulski Cezary, Dębniak Tadeusz, Tołoczko-Grabarek Aleksandra, Oszurek Oleg, Jakubowska Anna, Morawski Antoni, and Lubiński Jan
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Published
- 2012
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4. Serum concentration of selected macro- and microelements and their correlation with the risk of breast and ovarian cancer among BRCA1 mutation carriers
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Muszyńska Magdalena, Sukiennicki Grzegorz, Huzarski Tomasz, Gronwald Jacek, Cybulski Cezary, Dębniak Tadeusz, Tołoczko-Grabarek Aleksandra, Ashuryk Oleg, Jakubowska Anna, Morawski Antoni, and Lubiński Jan
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Published
- 2012
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5. Serum concentration of iron as predictor of cancer risk among BRCA1 mutation carriers
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Sukiennicki Grzegorz, Muszyńska Magdalena, Huzarski Tomasz, Gronwald Jacek, Cybulski Cezary, Dębniak Tadeusz, Tołoczko-Grabarek Aleksandra, Ashuryk Oleg, Jakubowska Anna, Morawski Antoni, and Lubiński Jan
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Published
- 2012
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6. Population Screening for Cancer Family Syndromes in the West Pomeranian Region of Poland
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Gronwald Jacek, Raczyński Andrzej, Tarhoni Mariusz, Blachowski Mirosław, Huzarski Tomasz, Byrski Tomasz, Tołoczko-Grabarek Aleksandra, Dębniak Tadeusz, Cybulski Cezary, Huzarska Jowita, Oszurek Oleg, and Lubiński Jan
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population screening ,cancer family syndromes ,familial doctors ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Published
- 2006
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7. Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women.
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Rebbeck, Timothy R, Friebel, Tara M, Mitra, Nandita, Wan, Fei, Chen, Stephanie, Andrulis, Irene L, Apostolou, Paraskevi, Arnold, Norbert, Arun, Banu K, Barrowdale, Daniel, Benitez, Javier, Berger, Raanan, Berthet, Pascaline, Borg, Ake, Buys, Saundra S, Caldes, Trinidad, Carter, Jonathan, Chiquette, Jocelyne, Claes, Kathleen BM, Couch, Fergus J, Cybulski, Cezary, Daly, Mary B, de la Hoya, Miguel, Diez, Orland, Domchek, Susan M, Nathanson, Katherine L, Durda, Katarzyna, Ellis, Steve, EMBRACE, Evans, D Gareth, Foretova, Lenka, Friedman, Eitan, Frost, Debra, Ganz, Patricia A, Garber, Judy, Glendon, Gord, Godwin, Andrew K, Greene, Mark H, Gronwald, Jacek, Hahnen, Eric, Hallberg, Emily, Hamann, Ute, Hansen, Thomas VO, HEBON, Imyanitov, Evgeny N, Isaacs, Claudine, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, John, Esther M, Karlan, Beth Y, Kaufman, Bella, Investigators, KConFab, Kwong, Ava, Laitman, Yael, Lasset, Christine, Lazaro, Conxi, Lester, Jenny, Loman, Niklas, Lubinski, Jan, Manoukian, Siranoush, Mitchell, Gillian, Montagna, Marco, Neuhausen, Susan L, Nevanlinna, Heli, Niederacher, Dieter, Nussbaum, Robert L, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I, Park, Sue Kyung, Piedmonte, Marion, Radice, Paolo, Rappaport-Fuerhauser, Christine, Rookus, Matti A, Seynaeve, Caroline, Simard, Jacques, Singer, Christian F, Soucy, Penny, Southey, Melissa, Stoppa-Lyonnet, Dominique, Sukiennicki, Grzegorz, Szabo, Csilla I, Tancredi, Mariella, Teixeira, Manuel R, Teo, Soo-Hwang, Terry, Mary Beth, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda Ewart, Toloczko-Grabarek, Aleksandra, Tung, Nadine, van Rensburg, Elizabeth J, Villano, Danylo, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weitzel, Jeffrey N, Zidan, Jamal, and Zorn, Kristin K
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EMBRACE ,HEBON ,Humans ,Breast Neoplasms ,Population Surveillance ,Heterozygote ,Phenotype ,Loss of Heterozygosity ,Germ-Line Mutation ,Alleles ,Genes ,BRCA1 ,Genes ,BRCA2 ,Exons ,Female ,Promoter Regions ,Genetic ,BRCA1 ,BRCA2 ,Hereditary breast and ovarian cancer ,Transheterozygosity ,Genes ,Promoter Regions ,Genetic ,Clinical Research ,Breast Cancer ,Cancer ,2.1 Biological and endogenous factors ,Oncology & Carcinogenesis ,Oncology and Carcinogenesis - Abstract
BackgroundMost BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood.MethodsFrom 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2.ResultsThe majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p
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- 2016
8. A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases
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Meagher, Nicola S., Wang, Linyuan, Rambau, Peter F., Intermaggio, Maria P., Huntsman, David G., Wilkens, Lynne R., El-Bahrawy, Mona A., Ness, Roberta B., Odunsi, Kunle, Steed, Helen, Herpel, Esther, Anglesio, Michael S., Zhang, Bonnie, Lambie, Neil, Swerdlow, Anthony J., Lubiński, Jan, Vierkant, Robert A., Goode, Ellen L., Menon, Usha, Toloczko-Grabarek, Aleksandra, Oszurek, Oleg, Bilic, Sanela, Talhouk, Aline, García-Closas, Montserrat, Wang, Qin, Tan, Adeline, Farrell, Rhonda, Kennedy, Catherine J., Jimenez-Linan, Mercedes, Sundfeldt, Karin, Etter, John L., Menkiszak, Janusz, Goodman, Marc T., Klonowski, Paul, Leung, Yee, Winham, Stacey J., Moysich, Kirsten B., Behrens, Sabine, Kluz, Tomasz, Edwards, Robert P., Gronwald, Jacek, Modugno, Francesmary, Hernandez, Brenda Y, Chow, Christine, Kelemen, Linda E., Keeney, Gary L., Carney, Michael E., Natanzon, Yanina, Robertson, Gregory, Sharma, Raghwa, Gayther, Simon A., Alsop, Jennifer, Luk, Hugh, Karpinskyj, Chloe, Campbell, Ian, Sinn, Peter, Gentry-Maharaj, Aleksandra, Coulson, Penny, Chang-Claude, Jenny, Shah, Mitul, Widschwendter, Martin, Tang, Katrina, Schoemaker, Minouk J., Koziak, Jennifer M., Cook, Linda S., Brenton, James D., Daley, Frances, Kristjansdottir, Björg, Mateoiu, Constantina, Larson, Melissa C., Harnett, Paul R., Jung, Audrey, deFazio, Anna, Gorringe, Kylie L., Pharoah, Paul D.P., Minoo, Parham, Stewart, Colin, Bathe, Oliver F., Gui, Xianyong, Cohen, Paul, Ramus, Susan J., and Köbel, Martin
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- 2019
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9. Validated biomarker assays confirm that ARID1A loss is confounded with MMR deficiency, CD8(+) TIL infiltration, and provides no independent prognostic value in endometriosis-associated ovarian carcinomas
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Heinze, K, Nazeran, TM, Lee, S, Kramer, P, Cairns, ES, Chiu, DS, Leung, SCY, Kang, EY, Meagher, NS, Kennedy, CJ, Boros, J, Kommoss, F, Vollert, H-W, Heitze, F, du Bois, A, Harter, P, Grube, M, Kraemer, B, Staebler, A, Kommoss, FKF, Heublein, S, Sinn, H-P, Singh, N, Laslavic, A, Elishaev, E, Olawaiye, A, Moysich, K, Modugno, F, Sharma, R, Brand, AH, Harnett, PR, DeFazio, A, Fortner, RT, Lubinski, J, Lener, M, Toloczko-Grabarek, A, Cybulski, C, Gronwald, H, Gronwald, J, Coulson, P, El-Bahrawy, MA, Jones, ME, Schoemaker, MJ, Swerdlow, AJ, Gorringe, KL, Campbell, I, Cook, L, Gayther, SA, Carney, ME, Shvetsov, YB, Hernandez, BY, Wilkens, LR, Goodman, MT, Mateoiu, C, Linder, A, Sundfeldt, K, Kelemen, LE, Gentry-Maharaj, A, Widschwendter, M, Menon, U, Bolton, KL, Alsop, J, Shah, M, Jimenez-Linan, M, Pharoah, PDP, Brenton, JD, Cushing-Haugen, KL, Harris, HR, Doherty, JA, Gilks, B, Ghatage, P, Huntsman, DG, Nelson, GS, Tinker, A, Lee, C-H, Goode, EL, Nelson, BH, Ramus, SJ, Kommoss, S, Talhouk, A, Kobel, M, Anglesio, MS, Heinze, K, Nazeran, TM, Lee, S, Kramer, P, Cairns, ES, Chiu, DS, Leung, SCY, Kang, EY, Meagher, NS, Kennedy, CJ, Boros, J, Kommoss, F, Vollert, H-W, Heitze, F, du Bois, A, Harter, P, Grube, M, Kraemer, B, Staebler, A, Kommoss, FKF, Heublein, S, Sinn, H-P, Singh, N, Laslavic, A, Elishaev, E, Olawaiye, A, Moysich, K, Modugno, F, Sharma, R, Brand, AH, Harnett, PR, DeFazio, A, Fortner, RT, Lubinski, J, Lener, M, Toloczko-Grabarek, A, Cybulski, C, Gronwald, H, Gronwald, J, Coulson, P, El-Bahrawy, MA, Jones, ME, Schoemaker, MJ, Swerdlow, AJ, Gorringe, KL, Campbell, I, Cook, L, Gayther, SA, Carney, ME, Shvetsov, YB, Hernandez, BY, Wilkens, LR, Goodman, MT, Mateoiu, C, Linder, A, Sundfeldt, K, Kelemen, LE, Gentry-Maharaj, A, Widschwendter, M, Menon, U, Bolton, KL, Alsop, J, Shah, M, Jimenez-Linan, M, Pharoah, PDP, Brenton, JD, Cushing-Haugen, KL, Harris, HR, Doherty, JA, Gilks, B, Ghatage, P, Huntsman, DG, Nelson, GS, Tinker, A, Lee, C-H, Goode, EL, Nelson, BH, Ramus, SJ, Kommoss, S, Talhouk, A, Kobel, M, and Anglesio, MS
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- 2022
10. Plasma micronutrients, trace elements, and breast cancer in BRCA1 mutation carriers: an exploratory study
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Kotsopoulos, Joanne, Sukiennicki, Grzegorz, Muszyńska, Magdalena, Gackowski, Daniel, Kąklewski, Krzysztof, Durda, Katarzyna, Jaworska, Katarzyna, Huzarski, Tomasz, Gronwald, Jacek, Byrski, Tomasz, Ashuryk, Oleg, Dębniak, Tadeusz, Tołoczko-Grabarek, Aleksandra, Stawicka, Małgorzata, Godlewski, Dariusz, Oliński, Ryszard, Jakubowska, Anna, Narod, Steven A., and Lubinski, Jan
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- 2012
11. CHAPTER 22. Selenium and Cancer
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Jaworska-Bieniek, Katarzyna, primary, Lener, Marcin, additional, Muszynska, Magdalena, additional, Serrano-Fernández, Pablo, additional, Sukiennicki, Grzegorz, additional, Durda, Katarzyna, additional, Gromowski, Tomasz, additional, Gupta, Satish, additional, Kladny, Józef, additional, Wiechowska-Kozlowska, Anna, additional, Grodzki, Tomasz, additional, Jaworowska, Ewa, additional, Lubinski, Jakub, additional, Górecka-Szyld, Barbara, additional, Wilk, Grazyna, additional, Huzarski, Tomasz, additional, Byrski, Tomasz, additional, Cybulski, Cezary, additional, Gronwald, Jacek, additional, Debniak, Tadeusz, additional, Ashuryk, Olgierd, additional, Toloczko-Grabarek, Aleksandra, additional, Morawski, Antoni, additional, Scott, Rodney J., additional, Jakubowska, Anna, additional, and Lubinski, Jan, additional
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- 2015
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12. Prognostic and Immunological Significance of ARID1A Status in Endometriosis-Associated Ovarian Carcinoma
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Heinze, Karolin, primary, Nazeran, Tayyebeh M, additional, Lee, Sandra, additional, Kraemer, Pauline, additional, Cairns, Evan S, additional, Chiu, Derek S, additional, Leung, Samuel CY, additional, Kang, Eun-Young, additional, Meagher, Nicola S, additional, Kennedy, Catherine J, additional, Boros, Jessica, additional, Kommoss, Friedrich, additional, Vollert, Hans-Walter, additional, Heitze, Florian, additional, du Bois, Andreas, additional, Harter, Philipp, additional, Grube, Marcel, additional, Kraemer, Bernhard, additional, Staebler, Annette, additional, Kommoss, Felix K.F, additional, Heublein, Sabine, additional, Sinn, Peter, additional, Singh, Naveena, additional, Laslavic, Angela, additional, Elishaev, Esther, additional, Olawaiye, Alex, additional, Moysich, Kirsten, additional, Modugno, Francesmary, additional, Sharma, Raghwa, additional, Brand, Alison H, additional, Harnett, Paul R, additional, deFazio, Anna, additional, Fortner, Renee T, additional, Lubinski, Jan, additional, Lener, Marcin, additional, Toloczko-Grabarek, Aleksandra, additional, Cybulski, Cezary, additional, Gronwald, Helena, additional, Gronwald, Jacek, additional, Coulson, Penny, additional, El-Bahrawy, Mona A, additional, Jones, Michael E, additional, Schoemaker, Minouk J, additional, Swerdlow, Anthony J, additional, Gorringe, Kylie L, additional, Campbell, Ian, additional, Cook, Linda, additional, Gayther, Simon A, additional, Carney, Michael E, additional, Shvetsov, Yurii B, additional, Hernandez, Brenda B, additional, Wilkens, Lynne R, additional, Goodman, Marc T, additional, Mateoiu, Constantina, additional, Linder, Anna, additional, Sundfeldt, Karin, additional, Kelemen, Linda E, additional, Gentry-Maharaj, Aleksandra, additional, Widschwendter, Martin, additional, Menon, Usha, additional, Bolton, Kelly L, additional, Alsop, Jennifer, additional, Shah, Mitul, additional, Jimenez-Linan, Mercedes, additional, Pharoah, Paul DP, additional, Brenton, James D, additional, Cushing-Haugen, Kara L, additional, Harris, Holly R, additional, Doherty, Jennifer A, additional, Gilks, Blake, additional, Ghatage, Prafull, additional, Huntsman, David G, additional, Nelson, Gregg S, additional, Tinker, Anna V, additional, Lee, Cheng-Han, additional, Goode, Ellen L, additional, Nelson, Brad H, additional, Ramus, Susan J, additional, Kommoss, Stefan, additional, Talhouk, Aline, additional, Koebel, Martin, additional, and Anglesio, Michael S, additional
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- 2021
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13. Association of Type and Location of BRCA1 and BRCA2 Mutations With Risk of Breast and Ovarian Cancer
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Rebbeck, Timothy R., Mitra, Nandita, Wan, Fei, Sinilnikova, Olga M., Healey, Sue, McGuffog, Lesley, Mazoyer, Sylvie, Chenevix-Trench, Georgia, Easton, Douglas F., Antoniou, Antonis C., Nathanson, Katherine L., Laitman, Yael, Kushnir, Anya, Paluch-Shimon, Shani, Berger, Raanan, Zidan, Jamal, Friedman, Eitan, Ehrencrona, Hans, Stenmark-Askmalm, Marie, Einbeigi, Zakaria, Loman, Niklas, Harbst, Katja, Rantala, Johanna, Melin, Beatrice, Huo, Dezheng, Olopade, Olufunmilayo I., Seldon, Joyce, Ganz, Patricia A., Nussbaum, Robert L., Chan, Salina B., Odunsi, Kunle, Gayther, Simon A., Domchek, Susan M., Arun, Banu K., Lu, Karen H., Mitchell, Gillian, Karlan, Beth Y., Walsh, Christine, Lester, Jenny, Godwin, Andrew K., Pathak, Harsh, Ross, Eric, Daly, Mary B., Whittemore, Alice S., John, Esther M., Miron, Alexander, Terry, Mary Beth, Chung, Wendy K., Goldgar, David E., Buys, Saundra S., Janavičius, Ramūnas, Tihomirova, Laima, Tung, Nadine, Dorfling, Cecilia M., van Rensburg, Elizabeth J., Steele, Linda, Neuhausen, Susan L., Ding, Yuan Chun, Ejlertsen, Bent, Gerdes, Anne-Marie, Hansen, Thomas v. O., Ramón y Cajal, Teresa, Osorio, Ana, Benitez, Javier, Godino, Javier, Tejada, Maria-Isabel, Duran, Mercedes, Weitzel, Jeffrey N., Bobolis, Kristie A, Sand, Sharon R., Fontaine, Annette, Savarese, Antonella, Pasini, Barbara, Peissel, Bernard, Bonanni, Bernardo, Zaffaroni, Daniela, Vignolo-Lutati, Francesca, Scuvera, Giulietta, Giannini, Giuseppe, Bernard, Loris, Genuardi, Maurizio, Radice, Paolo, Dolcetti, Riccardo, Manoukian, Siranoush, Pensotti, Valeria, Gismondi, Viviana, Yannoukakos, Drakoulis, Fostira, Florentia, Garber, Judy, Torres, Diana, Rashid, Muhammad Usman, Hamann, Ute, Peock, Susan, Frost, Debra, Platte, Radka, Evans, D. Gareth, Eeles, Rosalind, Davidson, Rosemarie, Eccles, Diana, Cole, Trevor, Cook, Jackie, Brewer, Carole, Hodgson, Shirley, Morrison, Patrick J., Walker, Lisa, Porteous, Mary E., Kennedy, M. John, Izatt, Louise, Adlard, Julian, Donaldson, Alan, Ellis, Steve, Sharma, Priyanka, Schmutzler, Rita Katharina, Wappenschmidt, Barbara, Becker, Alexandra, Rhiem, Kerstin, Hahnen, Eric, Engel, Christoph, Meindl, Alfons, Engert, Stefanie, Ditsch, Nina, Arnold, Norbert, Plendl, Hans Jörg, Mundhenke, Christoph, Niederacher, Dieter, Fleisch, Markus, Sutter, Christian, Bartram, C. R., Dikow, Nicola, Wang-Gohrke, Shan, Gadzicki, Dorothea, Steinemann, Doris, Kast, Karin, Beer, Marit, Varon-Mateeva, Raymonda, Gehrig, Andrea, Weber, Bernhard H., Stoppa-Lyonnet, Dominique, Sinilnikova, Olga M., Mazoyer, Sylvie, Houdayer, Claude, Belotti, Muriel, Gauthier-Villars, Marion, Damiola, Francesca, Boutry-Kryza, Nadia, Lasset, Christine, Sobol, Hagay, Peyrat, Jean-Philippe, Muller, Danièle, Fricker, Jean-Pierre, Collonge-Rame, Marie-Agnès, Mortemousque, Isabelle, Nogues, Catherine, Rouleau, Etienne, Isaacs, Claudine, De Paepe, Anne, Poppe, Bruce, Claes, Kathleen, De Leeneer, Kim, Piedmonte, Marion, Rodriguez, Gustavo, Wakely, Katie, Boggess, John, Blank, Stephanie V., Basil, Jack, Azodi, Masoud, Phillips, Kelly-Anne, Caldes, Trinidad, de la Hoya, Miguel, Romero, Atocha, Nevanlinna, Heli, Aittomäki, Kristiina, van der Hout, Annemarie H., Hogervorst, Frans B. L., Verhoef, Senno, Collée, J. Margriet, Seynaeve, Caroline, Oosterwijk, Jan C., Gille, Johannes J. P., Wijnen, Juul T., Garcia, Encarna B. Gómez, Kets, Carolien M., Ausems, Margreet G. E. M., Aalfs, Cora M., Devilee, Peter, Mensenkamp, Arjen R., Kwong, Ava, Olah, Edith, Papp, Janos, Diez, Orland, Lazaro, Conxi, Darder, Esther, Blanco, Ignacio, Salinas, Mónica, Jakubowska, Anna, Lubinski, Jan, Gronwald, Jacek, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Sukiennicki, Grzegorz, Huzarski, Tomasz, Byrski, Tomasz, Cybulski, Cezary, Toloczko-Grabarek, Aleksandra, Złowocka-Perłowska, Elżbieta, Menkiszak, Janusz, Arason, Adalgeir, Barkardottir, Rosa B., Simard, Jacques, Laframboise, Rachel, Montagna, Marco, Agata, Simona, Alducci, Elisa, Peixoto, Ana, Teixeira, Manuel R., Spurdle, Amanda B., Lee, Min Hyuk, Park, Sue K., Kim, Sung-Won, Friebel, Tara M., Couch, Fergus J., Lindor, Noralane M., Pankratz, Vernon S., Guidugli, Lucia, Wang, Xianshu, Tischkowitz, Marc, Foretova, Lenka, Vijai, Joseph, Offit, Kenneth, Robson, Mark, Rau-Murthy, Rohini, Kauff, Noah, Fink-Retter, Anneliese, Singer, Christian F., Rappaport, Christine, Gschwantler-Kaulich, Daphne, Pfeiler, Georg, Tea, Muy-Kheng, Berger, Andreas, Greene, Mark H., Mai, Phuong L., Imyanitov, Evgeny N., Toland, Amanda Ewart, Senter, Leigha, Bojesen, Anders, Pedersen, Inge Sokilde, Skytte, Anne-Bine, Sunde, Lone, Thomassen, Mads, Moeller, Sanne Traasdahl, Kruse, Torben A., Jensen, Uffe Birk, Caligo, Maria Adelaide, Aretini, Paolo, Teo, Soo-Hwang, Selkirk, Christina G., Hulick, Peter J., and Andrulis, Irene
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- 2015
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14. Additional file 1: Table S1. of Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women
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Rebbeck, Timothy, Friebel, Tara, Mitra, Nandita, Wan, Fei, Chen, Stephanie, Andrulis, Irene, Apostolou, Paraskevi, Arnold, Norbert, Arun, Banu, Barrowdale, Daniel, Benitez, Javier, Berger, Raanan, Berthet, Pascaline, Borg, Ake, Buys, Saundra, Caldes, Trinidad, Carter, Jonathan, Chiquette, Jocelyne, Claes, Kathleen, Couch, Fergus, Cybulski, Cezary, Daly, Mary, Hoya, Miguel De La, Diez, Orland, Domchek, Susan, Nathanson, Katherine, Durda, Katarzyna, Ellis, Steve, D. Evans, Foretova, Lenka, Friedman, Eitan, Frost, Debra, Ganz, Patricia, Garber, Judy, Gord Glendon, Godwin, Andrew, Greene, Mark, Gronwald, Jacek, Hahnen, Eric, Hallberg, Emily, Hamann, Ute, Hansen, Thomas, Imyanitov, Evgeny, Isaacs, Claudine, Jakubowska, Anna, Ramunas Janavicius, Jaworska-Bieniek, Katarzyna, John, Esther, Karlan, Beth, Kaufman, Bella, KConFab Investigators, Kwong, Ava, Laitman, Yael, Lasset, Christine, Conxi Lazaro, Lester, Jenny, Loman, Niklas, Lubinski, Jan, Manoukian, Siranoush, Mitchell, Gillian, Montagna, Marco, Neuhausen, Susan, Nevanlinna, Heli, Niederacher, Dieter, Nussbaum, Robert, Offit, Kenneth, Olah, Edith, Olufunmilayo Olopade, Park, Sue, Piedmonte, Marion, Radice, Paolo, Rappaport-Fuerhauser, Christine, Rookus, Matti, Seynaeve, Caroline, Simard, Jacques, Singer, Christian, Soucy, Penny, Southey, Melissa, Stoppa-Lyonnet, Dominique, Sukiennicki, Grzegorz, Szabo, Csilla, Tancredi, Mariella, Teixeira, Manuel, Soo-Hwang Teo, Terry, Mary, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda, Toloczko-Grabarek, Aleksandra, Tung, Nadine, Rensburg, Elizabeth Van, Villano, Danylo, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weitzel, Jeffrey, Zidan, Jamal, Zorn, Kristin, McGuffog, Lesley, Easton, Douglas, Chenevix-Trench, Georgia, Antoniou, Antonis, and Ramus, Susan
- Abstract
Ethics committees that granted approval for the access and use of the data for this study. Table S2. Participant counts by center and mutation. Table S3. Primers used for PCR and Sanger sequencing. Table S4. Primers used in micro-satellite analysis for loss of heterozygosity. Table S5. Micro-satellite loss of heterozygosity and sequencing analysis results. (DOC 177 kb)
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- 2016
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15. Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women
- Author
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University of Helsinki, Department of Obstetrics and Gynecology, Rebbeck, Timothy R., Friebel, Tara M., Mitra, Nandita, Wan, Fei, Chen, Stephanie, Andrulis, Irene L., Apostolou, Paraskevi, Arnold, Norbert, Arun, Banu K., Barrowdale, Daniel, Benitez, Javier, Berger, Raanan, Berthet, Pascaline, Borg, Ake, Buys, Saundra S., Caldes, Trinidad, Carter, Jonathan, Chiquette, Jocelyne, Claes, Kathleen B. M., Couch, Fergus J., Cybulski, Cezary, Daly, Mary B., de la Hoya, Miguel, Diez, Orland, Domchek, Susan M., Nathanson, Katherine L., Durda, Katarzyna, Ellis, Steve, Evans, D. Gareth, Foretova, Lenka, Friedman, Eitan, Frost, Debra, Ganz, Patricia A., Garber, Judy, Glendon, Gord, Godwin, Andrew K., Greene, Mark H., Gronwald, Jacek, Hahnen, Eric, Hallberg, Emily, Hamann, Ute, Hansen, Thomas V. O., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, John, Esther M., Karlan, Beth Y., Kaufman, Bella, Kwong, Ava, Laitman, Yael, Lasset, Christine, Lazaro, Conxi, Lester, Jenny, Loman, Niklas, Lubinski, Jan, Manoukian, Siranoush, Mitchell, Gillian, Montagna, Marco, Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Park, Sue Kyung, Piedmonte, Marion, Radice, Paolo, Rappaport-Fuerhauser, Christine, Rookus, Matti A., Seynaeve, Caroline, Simard, Jacques, Singer, Christian F., Soucy, Penny, Southey, Melissa, Stoppa-Lyonnet, Dominique, Sukiennicki, Grzegorz, Szabo, Csilla I., Tancredi, Mariella, Teixeira, Manuel R., Teo, Soo-Hwang, Terry, Mary Beth, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda Ewart, Toloczko-Grabarek, Aleksandra, Tung, Nadine, van Rensburg, Elizabeth J., Villano, Danylo, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weitzel, Jeffrey N., Zidan, Jamal, Zorn, Kristin K., McGuffog, Lesley, Easton, Douglas, Chenevix-Trench, Georgia, Antoniou, Antonis C., Ramus, Susan J., EMBRACE, HEBON, KConFab Investigators, University of Helsinki, Department of Obstetrics and Gynecology, Rebbeck, Timothy R., Friebel, Tara M., Mitra, Nandita, Wan, Fei, Chen, Stephanie, Andrulis, Irene L., Apostolou, Paraskevi, Arnold, Norbert, Arun, Banu K., Barrowdale, Daniel, Benitez, Javier, Berger, Raanan, Berthet, Pascaline, Borg, Ake, Buys, Saundra S., Caldes, Trinidad, Carter, Jonathan, Chiquette, Jocelyne, Claes, Kathleen B. M., Couch, Fergus J., Cybulski, Cezary, Daly, Mary B., de la Hoya, Miguel, Diez, Orland, Domchek, Susan M., Nathanson, Katherine L., Durda, Katarzyna, Ellis, Steve, Evans, D. Gareth, Foretova, Lenka, Friedman, Eitan, Frost, Debra, Ganz, Patricia A., Garber, Judy, Glendon, Gord, Godwin, Andrew K., Greene, Mark H., Gronwald, Jacek, Hahnen, Eric, Hallberg, Emily, Hamann, Ute, Hansen, Thomas V. O., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, John, Esther M., Karlan, Beth Y., Kaufman, Bella, Kwong, Ava, Laitman, Yael, Lasset, Christine, Lazaro, Conxi, Lester, Jenny, Loman, Niklas, Lubinski, Jan, Manoukian, Siranoush, Mitchell, Gillian, Montagna, Marco, Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Park, Sue Kyung, Piedmonte, Marion, Radice, Paolo, Rappaport-Fuerhauser, Christine, Rookus, Matti A., Seynaeve, Caroline, Simard, Jacques, Singer, Christian F., Soucy, Penny, Southey, Melissa, Stoppa-Lyonnet, Dominique, Sukiennicki, Grzegorz, Szabo, Csilla I., Tancredi, Mariella, Teixeira, Manuel R., Teo, Soo-Hwang, Terry, Mary Beth, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda Ewart, Toloczko-Grabarek, Aleksandra, Tung, Nadine, van Rensburg, Elizabeth J., Villano, Danylo, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weitzel, Jeffrey N., Zidan, Jamal, Zorn, Kristin K., McGuffog, Lesley, Easton, Douglas, Chenevix-Trench, Georgia, Antoniou, Antonis C., Ramus, Susan J., EMBRACE, HEBON, and KConFab Investigators
- Abstract
Background: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p <0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p <0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2.
- Published
- 2016
16. Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women
- Author
-
Rebbeck, R. (Timothy), Friebel, M.O.W. (Mark ), Mitra, N. (Nandita), Wan, F. (Fei), Chen, S. (Stephanie), Andrulis, I.L. (Irene), Apostolou, P. (Paraskevi), Arnold, N. (Norbert), Arun, B.K. (Banu), Barrowdale, D. (Daniel), Benítez, J. (Javier), Berger, R. (Raanan), Berthet, P. (Pascaline), Borg, Å. (Åke), Buys, S.S. (Saundra S.), Caldes, T. (Trinidad), Carter, J. (Jonathan), Chiquette, J. (Jocelyne), Claes, K.B.M. (Kathleen B.M.), Couch, F.J. (Fergus J.), Cybulski, C. (Cezary), Daly, M.B. (Mary), Hoya, M. (Miguel) de La, Díez, O. (Orland), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Durda, K. (Katarzyna), Ellis, S.D. (Steve), Evans, D.G. (D.Gareth), Foretova, L. (Lenka), Friedman, E. (Eitan), Frost, D. (Debra), Ganz, P.A. (Patricia), Garber, J. (Judy), Glendon, G. (Gord), Godwin, A.K. (Andrew), Greene, M.H. (Mark), Gronwald, J. (Jacek), Hahnen, E. (Eric), Hallberg, E. (Emily), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Jakubowska, A. (Anna), Janavicius, R. (Ramunas), Jaworska-Bieniek, K. (Katarzyna), John, E.M. (Esther), Karlan, B.Y. (Beth), Kaufman, B. (Bella), Kwong, A. (Ava), Laitman, Y. (Yael), Lasset, C. (Christine), Lázaro, C. (Conxi), Lester, K.J. (Kathryn), Loman, N. (Niklas), Lubinski, J. (Jan), Manoukian, S. (Siranoush), Mitchell, G. (Gillian), Montagna, M. (Marco), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Niederacher, D. (Dieter), Nussbaum, R. (Robert), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olofunmilayo), Park, S.K. (Sue K.), Piedmonte, M. (Marion), Radice, P. (Paolo), Rappaport-Fuerhauser, C. (Christine), Rookus, M.A. (Matti), Seynaeve, C.M. (Caroline), Simard, J. (Jacques), Singer, C.F. (Christian), Soucy, P. (Penny), Southey, M.C. (Melissa), Stoppa-Lyonnet, D. (Dominique), Sukiennicki, G. (Grzegorz), Szabo, C. (Csilla), Tancredi, M. (Mariella), Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, M.B. (Mary Beth), Thomassen, M. (Mads), Tihomirova, L. (Laima), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Toloczko-Grabarek, A. (Aleksandra), Tung, N. (Nadine), Rensburg, E.J. (Elizabeth) van, Villano, D. (Danylo), Wang-Gohrke, S. (Shan), Wapenschmidt, B. (Barbara), Weitzel, J.N. (Jeffrey), Zidan, J. (Jamal), Zorn, K.K. (Kristin K.), McGuffog, L. (Lesley), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Ramus, S.J. (Susan), Rebbeck, R. (Timothy), Friebel, M.O.W. (Mark ), Mitra, N. (Nandita), Wan, F. (Fei), Chen, S. (Stephanie), Andrulis, I.L. (Irene), Apostolou, P. (Paraskevi), Arnold, N. (Norbert), Arun, B.K. (Banu), Barrowdale, D. (Daniel), Benítez, J. (Javier), Berger, R. (Raanan), Berthet, P. (Pascaline), Borg, Å. (Åke), Buys, S.S. (Saundra S.), Caldes, T. (Trinidad), Carter, J. (Jonathan), Chiquette, J. (Jocelyne), Claes, K.B.M. (Kathleen B.M.), Couch, F.J. (Fergus J.), Cybulski, C. (Cezary), Daly, M.B. (Mary), Hoya, M. (Miguel) de La, Díez, O. (Orland), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Durda, K. (Katarzyna), Ellis, S.D. (Steve), Evans, D.G. (D.Gareth), Foretova, L. (Lenka), Friedman, E. (Eitan), Frost, D. (Debra), Ganz, P.A. (Patricia), Garber, J. (Judy), Glendon, G. (Gord), Godwin, A.K. (Andrew), Greene, M.H. (Mark), Gronwald, J. (Jacek), Hahnen, E. (Eric), Hallberg, E. (Emily), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Jakubowska, A. (Anna), Janavicius, R. (Ramunas), Jaworska-Bieniek, K. (Katarzyna), John, E.M. (Esther), Karlan, B.Y. (Beth), Kaufman, B. (Bella), Kwong, A. (Ava), Laitman, Y. (Yael), Lasset, C. (Christine), Lázaro, C. (Conxi), Lester, K.J. (Kathryn), Loman, N. (Niklas), Lubinski, J. (Jan), Manoukian, S. (Siranoush), Mitchell, G. (Gillian), Montagna, M. (Marco), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Niederacher, D. (Dieter), Nussbaum, R. (Robert), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olofunmilayo), Park, S.K. (Sue K.), Piedmonte, M. (Marion), Radice, P. (Paolo), Rappaport-Fuerhauser, C. (Christine), Rookus, M.A. (Matti), Seynaeve, C.M. (Caroline), Simard, J. (Jacques), Singer, C.F. (Christian), Soucy, P. (Penny), Southey, M.C. (Melissa), Stoppa-Lyonnet, D. (Dominique), Sukiennicki, G. (Grzegorz), Szabo, C. (Csilla), Tancredi, M. (Mariella), Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, M.B. (Mary Beth), Thomassen, M. (Mads), Tihomirova, L. (Laima), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Toloczko-Grabarek, A. (Aleksandra), Tung, N. (Nadine), Rensburg, E.J. (Elizabeth) van, Villano, D. (Danylo), Wang-Gohrke, S. (Shan), Wapenschmidt, B. (Barbara), Weitzel, J.N. (Jeffrey), Zidan, J. (Jamal), Zorn, K.K. (Kristin K.), McGuffog, L. (Lesley), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), and Ramus, S.J. (Susan)
- Abstract
Background: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2.
- Published
- 2016
- Full Text
- View/download PDF
17. Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women
- Author
-
Rebbeck, Timothy R., Friebel, Tara M., Mitra, Nandita, Wan, Fei, Chen, Stephanie, Andrulis, Irene L., Apostolou, Paraskevi, Arnold, Norbert, Arun, Banu K., Barrowdale, Daniel, Benitez, Javier, Berger, Raanan, Berthet, Pascaline, Borg, Ake, Buys, Saundra S., Caldes, Trinidad, Carter, Jonathan, Chiquette, Jocelyne, Claes, Kathleen B. M., Couch, Fergus J., Cybulski, Cezary, Daly, Mary B., de la Hoya, Miguel, Diez, Orland, Domchek, Susan M., Nathanson, Katherine L., Durda, Katarzyna, Ellis, Steve, Evans, D. Gareth, Foretova, Lenka, Friedman, Eitan, Frost, Debra, Ganz, Patricia A., Garber, Judy, Glendon, Gord, Godwin, Andrew K., Greene, Mark H., Gronwald, Jacek, Hahnen, Eric, Hallberg, Emily, Hamann, Ute, Hansen, Thomas V. O., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, John, Esther M., Karlan, Beth Y., Kaufman, Bella, Kwong, Ava, Laitman, Yael, Lasset, Christine, Lazaro, Conxi, Lester, Jenny, Loman, Niklas, Lubinski, Jan, Manoukian, Siranoush, Mitchell, Gillian, Montagna, Marco, Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Park, Sue Kyung, Piedmonte, Marion, Radice, Paolo, Rappaport-Fuerhauser, Christine, Rookus, Matti A., Seynaeve, Caroline, Simard, Jacques, Singer, Christian F., Soucy, Penny, Southey, Melissa, Stoppa-Lyonnet, Dominique, Sukiennicki, Grzegorz, Szabo, Csilla I., Tancredi, Mariella, Teixeira, Manuel R., Teo, Soo-Hwang, Terry, Mary Beth, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda Ewart, Toloczko-Grabarek, Aleksandra, Tung, Nadine, van Rensburg, Elizabeth J., Villano, Danylo, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weitzel, Jeffrey N., Zidan, Jamal, Zorn, Kristin K., McGuffog, Lesley, Easton, Douglas, Chenevix-Trench, Georgia, Antoniou, Antonis C., Ramus, Susan J., Rebbeck, Timothy R., Friebel, Tara M., Mitra, Nandita, Wan, Fei, Chen, Stephanie, Andrulis, Irene L., Apostolou, Paraskevi, Arnold, Norbert, Arun, Banu K., Barrowdale, Daniel, Benitez, Javier, Berger, Raanan, Berthet, Pascaline, Borg, Ake, Buys, Saundra S., Caldes, Trinidad, Carter, Jonathan, Chiquette, Jocelyne, Claes, Kathleen B. M., Couch, Fergus J., Cybulski, Cezary, Daly, Mary B., de la Hoya, Miguel, Diez, Orland, Domchek, Susan M., Nathanson, Katherine L., Durda, Katarzyna, Ellis, Steve, Evans, D. Gareth, Foretova, Lenka, Friedman, Eitan, Frost, Debra, Ganz, Patricia A., Garber, Judy, Glendon, Gord, Godwin, Andrew K., Greene, Mark H., Gronwald, Jacek, Hahnen, Eric, Hallberg, Emily, Hamann, Ute, Hansen, Thomas V. O., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, John, Esther M., Karlan, Beth Y., Kaufman, Bella, Kwong, Ava, Laitman, Yael, Lasset, Christine, Lazaro, Conxi, Lester, Jenny, Loman, Niklas, Lubinski, Jan, Manoukian, Siranoush, Mitchell, Gillian, Montagna, Marco, Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Park, Sue Kyung, Piedmonte, Marion, Radice, Paolo, Rappaport-Fuerhauser, Christine, Rookus, Matti A., Seynaeve, Caroline, Simard, Jacques, Singer, Christian F., Soucy, Penny, Southey, Melissa, Stoppa-Lyonnet, Dominique, Sukiennicki, Grzegorz, Szabo, Csilla I., Tancredi, Mariella, Teixeira, Manuel R., Teo, Soo-Hwang, Terry, Mary Beth, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda Ewart, Toloczko-Grabarek, Aleksandra, Tung, Nadine, van Rensburg, Elizabeth J., Villano, Danylo, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weitzel, Jeffrey N., Zidan, Jamal, Zorn, Kristin K., McGuffog, Lesley, Easton, Douglas, Chenevix-Trench, Georgia, Antoniou, Antonis C., and Ramus, Susan J.
- Abstract
Background: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). Cases were defined as TH, and controls were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 controls carried a BRCA1 mutation found in the TH case. Matched SH2 controls carried a BRCA2 mutation found in the TH case. After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2.
- Published
- 2016
18. Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women
- Author
-
Rebbeck, TR, Friebel, TM, Mitra, N, Wan, F, Chen, S, Andrulis, IL, Apostolou, P, Arnold, N, Arun, BK, Barrowdale, D, Benitez, J, Berger, R, Berthet, P, Borg, A, Buys, SS, Caldes, T, Carter, J, Chiquette, J, Claes, KBM, Couch, FJ, Cybulski, C, Daly, MB, de la Hoya, M, Diez, O, Domchek, SM, Nathanson, KL, Durda, K, Ellis, S, Evans, DG, Foretova, L, Friedman, E, Frost, D, Ganz, PA, Garber, J, Glendon, G, Godwin, AK, Greene, MH, Gronwald, J, Hahnen, E, Hallberg, E, Hamann, U, Hansen, TVO, Imyanitov, EN, Isaacs, C, Jakubowska, A, Janavicius, R, Jaworska-Bieniek, K, John, EM, Karlan, BY, Kaufman, B, Kwong, A, Laitman, Y, Lasset, C, Lazaro, C, Lester, J, Loman, N, Lubinski, J, Manoukian, S, Mitchell, G, Montagna, M, Neuhausen, SL, Nevanlinna, H, Niederacher, D, Nussbaum, RL, Offit, K, Olah, E, Olopade, OI, Park, SK, Piedmonte, M, Radice, P, Rappaport-Fuerhauser, C, Rookus, MA, Seynaeve, C, Simard, J, Singer, CF, Soucy, P, Southey, M, Stoppa-Lyonnet, D, Sukiennicki, G, Szabo, CI, Tancredi, M, Teixeira, MR, Teo, S-H, Terry, MB, Thomassen, M, Tihomirova, L, Tischkowitz, M, Toland, AE, Toloczko-Grabarek, A, Tung, N, van Rensburg, EJ, Villano, D, Wang-Gohrke, S, Wappenschmidt, B, Weitzel, JN, Zidan, J, Zorn, KK, McGuffog, L, Easton, D, Chenevix-Trench, G, Antoniou, AC, Ramus, SJ, Rebbeck, TR, Friebel, TM, Mitra, N, Wan, F, Chen, S, Andrulis, IL, Apostolou, P, Arnold, N, Arun, BK, Barrowdale, D, Benitez, J, Berger, R, Berthet, P, Borg, A, Buys, SS, Caldes, T, Carter, J, Chiquette, J, Claes, KBM, Couch, FJ, Cybulski, C, Daly, MB, de la Hoya, M, Diez, O, Domchek, SM, Nathanson, KL, Durda, K, Ellis, S, Evans, DG, Foretova, L, Friedman, E, Frost, D, Ganz, PA, Garber, J, Glendon, G, Godwin, AK, Greene, MH, Gronwald, J, Hahnen, E, Hallberg, E, Hamann, U, Hansen, TVO, Imyanitov, EN, Isaacs, C, Jakubowska, A, Janavicius, R, Jaworska-Bieniek, K, John, EM, Karlan, BY, Kaufman, B, Kwong, A, Laitman, Y, Lasset, C, Lazaro, C, Lester, J, Loman, N, Lubinski, J, Manoukian, S, Mitchell, G, Montagna, M, Neuhausen, SL, Nevanlinna, H, Niederacher, D, Nussbaum, RL, Offit, K, Olah, E, Olopade, OI, Park, SK, Piedmonte, M, Radice, P, Rappaport-Fuerhauser, C, Rookus, MA, Seynaeve, C, Simard, J, Singer, CF, Soucy, P, Southey, M, Stoppa-Lyonnet, D, Sukiennicki, G, Szabo, CI, Tancredi, M, Teixeira, MR, Teo, S-H, Terry, MB, Thomassen, M, Tihomirova, L, Tischkowitz, M, Toland, AE, Toloczko-Grabarek, A, Tung, N, van Rensburg, EJ, Villano, D, Wang-Gohrke, S, Wappenschmidt, B, Weitzel, JN, Zidan, J, Zorn, KK, McGuffog, L, Easton, D, Chenevix-Trench, G, Antoniou, AC, and Ramus, SJ
- Abstract
BACKGROUND: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. METHODS: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. RESULTS: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. CONCLUSIONS: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2.
- Published
- 2016
19. Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer
- Author
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Rebbeck, R. (Timothy), Mitra, N. (Nandita), Wan, F. (Fei), Sinilnikova, O. (Olga), Healey, S. (Sue), McGuffog, L. (Lesley), Chenevix-Trench, G. (Georgia), Easton, D.F. (Douglas), Antoniou, A.C. (Antonis), Nathanson, K.L. (Katherine), Laitman, Y. (Yael), Kushnir, A. (Anya), Paluch-Shimon, S. (Shani), Berger, R. (Raanan), Zidan, J. (Jamal), Friedman, E. (Eitan), Ehrencrona, H. (Hans), Stenmark-Askmalm, M. (Marie), Einbeigi, Z. (Zakaria), Loman, N. (Niklas), Harbst, K. (Katja), Rantala, J. (Johanna), Melin, B. (Beatrice), Huo, D. (Dezheng), Olopade, O.I. (Olofunmilayo), Seldon, J.L. (Joyce), Ganz, P.A. (Patricia), Nussbaum, R.L. (Robert L.), Chan, S. (Salina), Odunsi, K. (Kunle), Gayther, S.A. (Simon), Domchek, S.M. (Susan), Arun, B.K. (Banu), Lu, K.H. (Karen), Mitchell, G. (Gillian), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Godwin, A.K. (Andrew), Pathak, S.S., Ross, E.B. (Eric), Daly, M.J. (Mark), Whittemore, A.S. (Alice), John, E.M. (Esther), Miron, A. (Alexander), Terry, M.B. (Mary Beth), Chung, W.K. (Wendy K.), Goldgar, D. (David), Buys, S.S. (Saundra), Janavicius, R. (Ramunas), Tihomirova, L. (Laima), Tung, N. (Nadine), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Steele, L. (Linda), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Ejlertsen, B. (Bent), Gerdes, A-M. (Anne-Marie), Hansen, T.V.O. (Thomas), Ramon Y Cajal, T., Osorio, A. (Ana), Benítez, J. (Javier), Godino, J. (Javier), Tejada, M.I., Duran, M. (Mercedes), Weitzel, J.N. (Jeffrey), Bobolis, K.A. (Kristie A.), Sand, S.R. (Sharon), Fontaine, A. (Annette), Savarese, A. (Antonella), Pasini, B. (Barbara), Peissel, B. (Bernard), Bonnani, B. (Bernardo), Zaffaroni, D. (Daniela), Vignolo-Lutati, F. (Francesca), Scuvera, G. (Giulietta), Giannini, G. (Giuseppe), Bernard, L. (Loris), Genuardi, M. (Maurizio), Radice, P. (Paolo), Dolcetti, R. (Riccardo), Manoukian, S. (Siranoush), Pensotti, V. (Valeria), Gismondi, V. (Viviana), Yannoukakos, D. (Drakoulis), Fostira, F. (Florentia), Garber, J. (Judy), Torres, D. (Diana), Rashid, M.U. (Muhammad), Hamann, U. (Ute), Peock, S. (Susan), Frost, D. (Debra), Platte, R. (Radka), Evans, D.G. (Gareth), Eeles, R. (Rosalind), Davidson, R. (Rosemarie), Eccles, D. (Diana), Cole, T. (Trevor), Cook, J. (Jackie), Brewer, C. (Carole), Hodgson, S. (Shirley), Morrison, P.J. (Patrick), Walker, L.J. (Lisa), Porteous, M.E. (Mary), Kennedy, M.J. (John), Izatt, L. (Louise), Adlard, L., Donaldson, A. (Alan), Ellis, S.D. (Steve), Sharma, P. (Priyanka), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Becker, A. (Alexandra), Rhiem, K. (Kerstin), Hahnen, E. (Eric), Engel, C. (Christoph), Meindl, A. (Alfons), Engert, S. (Stefanie), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Mundhenke, C. (Christoph), Niederacher, D. (Dieter), Fleisch, M.C. (Markus), Sutter, C. (Christian), Bartram, C.R. (Claus), Dikow, N. (Nicola), Wang-Gohrke, S. (Shan), Gadzicki, D. (Dorothea), Steinemann, D. (Doris), Kast, K. (Karin), Beer, M. (Marit), Varon-Mateeva, R. (Raymonda), Gehrig, P.A. (Paola A.), Weber, B.H.F. (Bernhard), Stoppa-Lyonnet, D. (Dominique), Belotti, M. (Muriel), Gauthier-Villars, M. (Marion), Damiola, F. (Francesca), Boutry-Kryza, N. (N.), Lasset, C. (Christine), Sobol, H. (Hagay), Peyrat, J.-P., Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Collonge-Rame, M.-A., Mortemousque, I. (Isabelle), Nogues, C. (Catherine), Rouleau, E. (Etienne), Isaacs, C. (Claudine), Paepe, A. (Anne) de, Poppe, B. (Bruce), Claes, K. (Kathleen), De Leeneer, K. (Kim), Piedmonte, M. (Marion), Rodriguez, G. (Gustavo), Wakely, K. (Katie), Boggess, J.F. (John), Blank, S.V. (Stephanie), Basil, J. (Jack), Azodi, M. (Masoud), Phillips, K.-A. (Kelly-Anne), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Romero, A. (Atocha), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Hout, A.H. (Annemarie) van der, Hogervorst, F.B.L. (Frans), Verhoef, S., Collée, J.M. (Margriet), Seynaeve, C.M. (Caroline), Oosterwijk, J.C. (Jan), Gille, J.J. (Johan), Wijnen, J.T. (Juul), Gómez García, E.B. (Encarna), Kets, C.M. (Marleen), Ausems, M.G.E.M. (Margreet), Aalfs, C.M. (Cora), Devilee, P. (Peter), Mensenkamp, A.R. (Arjen), Kwong, A. (Ava), Olah, E., Papp, J. (Janos), Díez, O. (Orland), Lázaro, C. (Conxi), Darder, E. (Esther), Blanco, I. (Ignacio), Salinas, M., Jakubowska, A. (Anna), Lubinski, J. (Jan), Gronwald, J. (Jacek), Jaworska-Bieniek, K. (Katarzyna), Durda, K. (Katarzyna), Sukiennicki, G. (Grzegorz), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Cybulski, C. (Cezary), Toloczko-Grabarek, A. (Aleksandra), Złowocka-Perłowska, E. (Elzbieta), Menkiszak, J. (Janusz), Arason, A. (Adalgeir), Barkardottir, R.B. (Rosa), Simard, J. (Jacques), Laframboise, R. (Rachel), Montagna, M. (Marco), Agata, S. (Simona), Alducci, E. (Elisa), Peixoto, A. (Ana), Teixeira, P.J., Spurdle, A.B. (Amanda), Lee, M.H. (Min Hyuk), Park, S.K. (Sue), Kim, S.-W. (Sung-Won), Friebel, M.O.W. (Mark ), Couch, F.J. (Fergus), Lindor, N.M. (Noralane), Pankratz, V.S. (Shane), Guidugli, L. (Lucia), Wang, X. (Xianshu), Tischkowitz, M. (Marc), Foretova, L. (Lenka), Vijai, J. (Joseph), Offit, K. (Kenneth), Robson, M. (Mark), Rau-Murthy, R. (Rohini), Kauff, N. (Noah), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Gschwantler-Kaulich, D. (Daphne), Pfeiler, G. (Georg), Tea, M.-K., Berger, A. (Andreas), Greene, M.H. (Mark), Mai, P.L. (Phuong), Imyanitov, E.N. (Evgeny), Toland, A.E. (Amanda), Senter, L. (Leigha), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Skytte, A.-B. (Anne-Bine), Sunde, L. (Lone), Thomassen, M. (Mads), Moeller, S.T. (Sanne Traasdahl), Kruse, T.A. (Torben), Jensen, U.B., Caligo, M.A. (Maria), Aretini, P. (Paolo), Teo, S.-H. (Soo-Hwang), Selkirk, C.G. (Christina), Hulick, P.J. (Peter), Andrulis, I.L. (Irene), Rebbeck, R. (Timothy), Mitra, N. (Nandita), Wan, F. (Fei), Sinilnikova, O. (Olga), Healey, S. (Sue), McGuffog, L. (Lesley), Chenevix-Trench, G. (Georgia), Easton, D.F. (Douglas), Antoniou, A.C. (Antonis), Nathanson, K.L. (Katherine), Laitman, Y. (Yael), Kushnir, A. (Anya), Paluch-Shimon, S. (Shani), Berger, R. (Raanan), Zidan, J. (Jamal), Friedman, E. (Eitan), Ehrencrona, H. (Hans), Stenmark-Askmalm, M. (Marie), Einbeigi, Z. (Zakaria), Loman, N. (Niklas), Harbst, K. (Katja), Rantala, J. (Johanna), Melin, B. (Beatrice), Huo, D. (Dezheng), Olopade, O.I. (Olofunmilayo), Seldon, J.L. (Joyce), Ganz, P.A. (Patricia), Nussbaum, R.L. (Robert L.), Chan, S. (Salina), Odunsi, K. (Kunle), Gayther, S.A. (Simon), Domchek, S.M. (Susan), Arun, B.K. (Banu), Lu, K.H. (Karen), Mitchell, G. (Gillian), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Godwin, A.K. (Andrew), Pathak, S.S., Ross, E.B. (Eric), Daly, M.J. (Mark), Whittemore, A.S. (Alice), John, E.M. (Esther), Miron, A. (Alexander), Terry, M.B. (Mary Beth), Chung, W.K. (Wendy K.), Goldgar, D. (David), Buys, S.S. (Saundra), Janavicius, R. (Ramunas), Tihomirova, L. (Laima), Tung, N. (Nadine), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Steele, L. (Linda), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Ejlertsen, B. (Bent), Gerdes, A-M. (Anne-Marie), Hansen, T.V.O. (Thomas), Ramon Y Cajal, T., Osorio, A. (Ana), Benítez, J. (Javier), Godino, J. (Javier), Tejada, M.I., Duran, M. (Mercedes), Weitzel, J.N. (Jeffrey), Bobolis, K.A. (Kristie A.), Sand, S.R. (Sharon), Fontaine, A. (Annette), Savarese, A. (Antonella), Pasini, B. (Barbara), Peissel, B. (Bernard), Bonnani, B. (Bernardo), Zaffaroni, D. (Daniela), Vignolo-Lutati, F. (Francesca), Scuvera, G. (Giulietta), Giannini, G. (Giuseppe), Bernard, L. (Loris), Genuardi, M. (Maurizio), Radice, P. (Paolo), Dolcetti, R. (Riccardo), Manoukian, S. (Siranoush), Pensotti, V. (Valeria), Gismondi, V. (Viviana), Yannoukakos, D. (Drakoulis), Fostira, F. (Florentia), Garber, J. (Judy), Torres, D. (Diana), Rashid, M.U. (Muhammad), Hamann, U. (Ute), Peock, S. (Susan), Frost, D. (Debra), Platte, R. (Radka), Evans, D.G. (Gareth), Eeles, R. (Rosalind), Davidson, R. (Rosemarie), Eccles, D. (Diana), Cole, T. (Trevor), Cook, J. (Jackie), Brewer, C. (Carole), Hodgson, S. (Shirley), Morrison, P.J. (Patrick), Walker, L.J. (Lisa), Porteous, M.E. (Mary), Kennedy, M.J. (John), Izatt, L. (Louise), Adlard, L., Donaldson, A. (Alan), Ellis, S.D. (Steve), Sharma, P. (Priyanka), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Becker, A. (Alexandra), Rhiem, K. (Kerstin), Hahnen, E. (Eric), Engel, C. (Christoph), Meindl, A. (Alfons), Engert, S. (Stefanie), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Mundhenke, C. (Christoph), Niederacher, D. (Dieter), Fleisch, M.C. (Markus), Sutter, C. (Christian), Bartram, C.R. (Claus), Dikow, N. (Nicola), Wang-Gohrke, S. (Shan), Gadzicki, D. (Dorothea), Steinemann, D. (Doris), Kast, K. (Karin), Beer, M. (Marit), Varon-Mateeva, R. (Raymonda), Gehrig, P.A. (Paola A.), Weber, B.H.F. (Bernhard), Stoppa-Lyonnet, D. (Dominique), Belotti, M. (Muriel), Gauthier-Villars, M. (Marion), Damiola, F. (Francesca), Boutry-Kryza, N. (N.), Lasset, C. (Christine), Sobol, H. (Hagay), Peyrat, J.-P., Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Collonge-Rame, M.-A., Mortemousque, I. (Isabelle), Nogues, C. (Catherine), Rouleau, E. (Etienne), Isaacs, C. (Claudine), Paepe, A. (Anne) de, Poppe, B. (Bruce), Claes, K. (Kathleen), De Leeneer, K. (Kim), Piedmonte, M. (Marion), Rodriguez, G. (Gustavo), Wakely, K. (Katie), Boggess, J.F. (John), Blank, S.V. (Stephanie), Basil, J. (Jack), Azodi, M. (Masoud), Phillips, K.-A. (Kelly-Anne), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Romero, A. (Atocha), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Hout, A.H. (Annemarie) van der, Hogervorst, F.B.L. (Frans), Verhoef, S., Collée, J.M. (Margriet), Seynaeve, C.M. (Caroline), Oosterwijk, J.C. (Jan), Gille, J.J. (Johan), Wijnen, J.T. (Juul), Gómez García, E.B. (Encarna), Kets, C.M. (Marleen), Ausems, M.G.E.M. (Margreet), Aalfs, C.M. (Cora), Devilee, P. (Peter), Mensenkamp, A.R. (Arjen), Kwong, A. (Ava), Olah, E., Papp, J. (Janos), Díez, O. (Orland), Lázaro, C. (Conxi), Darder, E. (Esther), Blanco, I. (Ignacio), Salinas, M., Jakubowska, A. (Anna), Lubinski, J. (Jan), Gronwald, J. (Jacek), Jaworska-Bieniek, K. (Katarzyna), Durda, K. (Katarzyna), Sukiennicki, G. (Grzegorz), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Cybulski, C. (Cezary), Toloczko-Grabarek, A. (Aleksandra), Złowocka-Perłowska, E. (Elzbieta), Menkiszak, J. (Janusz), Arason, A. (Adalgeir), Barkardottir, R.B. (Rosa), Simard, J. (Jacques), Laframboise, R. (Rachel), Montagna, M. (Marco), Agata, S. (Simona), Alducci, E. (Elisa), Peixoto, A. (Ana), Teixeira, P.J., Spurdle, A.B. (Amanda), Lee, M.H. (Min Hyuk), Park, S.K. (Sue), Kim, S.-W. (Sung-Won), Friebel, M.O.W. (Mark ), Couch, F.J. (Fergus), Lindor, N.M. (Noralane), Pankratz, V.S. (Shane), Guidugli, L. (Lucia), Wang, X. (Xianshu), Tischkowitz, M. (Marc), Foretova, L. (Lenka), Vijai, J. (Joseph), Offit, K. (Kenneth), Robson, M. (Mark), Rau-Murthy, R. (Rohini), Kauff, N. (Noah), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Gschwantler-Kaulich, D. (Daphne), Pfeiler, G. (Georg), Tea, M.-K., Berger, A. (Andreas), Greene, M.H. (Mark), Mai, P.L. (Phuong), Imyanitov, E.N. (Evgeny), Toland, A.E. (Amanda), Senter, L. (Leigha), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Skytte, A.-B. (Anne-Bine), Sunde, L. (Lone), Thomassen, M. (Mads), Moeller, S.T. (Sanne Traasdahl), Kruse, T.A. (Torben), Jensen, U.B., Caligo, M.A. (Maria), Aretini, P. (Paolo), Teo, S.-H. (Soo-Hwang), Selkirk, C.G. (Christina), Hulick, P.J. (Peter), and Andrulis, I.L. (Irene)
- Abstract
Importance: Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. Objective: To identify mutation-specific cancer risks for carriers of BRCA1/2. Design, Setting, and Participants: Observational study ofwomen whowere ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19 581 carriers of BRCA1 mutations and 11 900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents.We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position.We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. Exposures: Mutations of BRCA1 or BRCA2. Main Outcomes and Measures: Breast and ovarian cancer risks. Results: Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95%CI, 1.22-1.74; P = 2 × 10-6), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95%CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95%CI, 1.22-1.55; P = 6 × 10-9).We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95%CI, 0.56-0.70; P = 9 × 10-17). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95%CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95%CI, 1.10-2.40; P = .01), and c.7394 to
- Published
- 2015
- Full Text
- View/download PDF
20. Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers
- Author
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Ramus, Susan J., Antoniou, Antonis C., Kuchenbaecker, Karoline B., Penny, Soucy, Jonathan, Beesley, Xiaoqing, Chen, Lesley, Mcguffog, Sinilnikova, Olga M., Sue, Healey, Daniel, Barrowdale, Andrew, Lee, Mads, Thomassen, Anne Marie Gerdes, Kruse, Torben A., Uffe Birk Jensen, Anne Bine Skytte, Caligo, Maria A., Annelie, Liljegren, Annika, Lindblom, Hakan, Olsson, Ulf, Kristoffersson, Marie Stenmark Askmalm, Swe Brca Melin, B., Swe, Brca, Domchek, Susan M., Domchek, Sm, Nathanson, Katherine L., Rebbeck, Timothy R., Anna, Jakubowska, Jan, Lubinski, Katarzyna, Jaworska, Katarzyna, Durda, Elzbieta, Złowocka, Jacek, Gronwald, Tomasz, Huzarski, Tomasz, Byrski, Cezary, Cybulski, Aleksandra Toloczko Grabarek, Ana, Osorio, Javier, Benitez, Mercedes, Duran, Maria Isabel Tejada, Ute, Hamann, Matti, Rookus, Van Leeuwen, Flora E., Aalfs, Cora M., Meijers Heijboer, Hanne E. J., Van Asperen, Christi J., Van Roozendaal, K. E. P., Nicoline, Hoogerbrugge, Collee, Margriet J., Margriet Collee, J., Mieke, Kriege, Hebon Van Der Luijt, R. B., Embrace, Embrace, Hebon, Susan, Peock, Debra, Frost, Ellis, Steve D., Radka, Platte, Elena, Fineberg, Gareth Evans, D., Fiona, Lalloo, Chris, Jacobs, Ros, Eeles, Julian, Adlard, Rosemarie, Davidson, Diana, Eccles, Trevor, Cole, Jackie, Cook, Joan, Paterson, Fiona, Douglas, Carole, Brewer, Shirley, Hodgson, Morrison, Patrick J., Lisa, Walker, Porteous, Mary E., John Kennedy, M., Harsh, Pathak, Godwin, Andrew K., Dominique Stoppa Lyonnet, Virginie Caux Moncoutier, Antoine Pauw, D. E., De Pauw, A., Marion Gauthier Villars, Sylvie, Mazoyer, Melanie, Leone, Alain, Calender, Christine, Lasset, Valerie, Bonadona, Agnes, Hardouin, Pascaline, Berthet, Yves Jean Bignon, Nancy, Uhrhammer, Laurence, Faivre, Catherine, Loustalot, Gemo, Saundra, Buys, Mary, Daly, Buys, Daly, S., Alex, Miron, Beth, Terry M., Mary Beth Terry, Terry, M. B., Chung, Wendy K., Esther, John M., John, Em, Melissa, Southey, David, Goldgar, Singer, Christian F., Muy Kheng Tea, Georg, Pfeiler, Anneliese Fink Retter, Hansen, Thomas V. O., Hansen, Tv, Bent, Ejlertsen, Oskar Th Johannsson, Kenneth, Offit, Tomas, Kirchhoff, Gaudet, Mia M., Joseph, Vijai, Mark, Robson, Marion, Piedmonte, Kelly Anne Phillips, Linda Van Le, Hoffman, James S., Amanda Ewart Toland, Ewart Toland, A., Marco, Montagna, Silvia, Tognazzo, Evgeny, Imyanitov, Claudine, Isaacs, Issacs, C., Ramunas, Janavicius, Conxi, Lazaro, Ignacio, Blanco, Eva, Tornero, Matilde, Navarro, Moysich, Kirsten B., Karlan, Beth Y., Jenny, Gross, Edith, Olah, Tibor, Vaszko, Soo Hwang Teo, Ganz, Patricia A., Beattie, Mary S., Dorfling, Cecelia M., Van Rensburg, Elizabeth J., Orland, Diez, Ava, Kwong, Schmutzler, Rita K., Barbara, Wappenschmidt, Christoph, Engel, Alfons, Meindl, Nina, Ditsch, Norbert, Arnold, Simone, Heidemann, Dieter, Niederacher, Sabine Preisler Adams, Dorotehea, Gadzicki, Raymonda Varon Mateeva, Helmut, Deissler, Andrea, Gehrig, Christian, Sutter, Karin, Kast, Britta, Fiebig, Dieter, Schafer, Trinidad, Caldes, Miguel De La Hoya, Heli, Nevanlinna, Kristiina, Aittomaki, Marie, Plante, Kconfab Spurdle, A. B., Kconfab, Neuhausen, Susan L., Neuhausen, Sl, Yuan Chun Ding, Xianshu, Wang, Noralane, Lindor, Zachary, Fredericksen, Shane Pankratz, V., Paolo, Peterlongo, Siranoush, Manoukian, Bernard, Peissel, Daniela, Zaffaroni, Bernardo, Bonanni, Loris, Bernard, Riccardo, Dolcetti, Laura, Papi, Ottini, Laura, Paolo, Radice, Greene, Mark H., Mai, Phuong L., Andrulis, Irene L., Gord, Glendon, Ocgn Ozcelik, H., Ocgn, Pharoah, Paul D. P., Pharoah, Pd, Gayther, Simon A., Jacques, Simard, Easton, Douglas F., Couch, Fergus J., Georgia Chenevix Trench, Behalf Of The Consortium Of Investigators Of Modifiers Of Brca1/2, O. N., Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Human Genetics, CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, Universitat de Barcelona, Genetica & Celbiologie, MUMC+: DA KG Lab Centraal Lab (9), RS: CARIM School for Cardiovascular Diseases, RS: GROW - School for Oncology and Reproduction, and Clinical Genetics
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Oncology ,endocrine system diseases ,[SDV]Life Sciences [q-bio] ,Càncer d'ovari ,DCN PAC - Perception action and control ,Cohort Studies ,Breast cancer ,0302 clinical medicine ,brca1 ,brca2 ,Odds Ratio ,Genetics (clinical) ,ComputingMilieux_MISCELLANEOUS ,Ovarian Neoplasms ,Genetics ,0303 health sciences ,education.field_of_study ,BRCA1 Protein ,Hazard ratio ,Middle Aged ,3. Good health ,ovarian cancer ,030220 oncology & carcinogenesis ,Female ,Adult ,Heterozygote ,medicine.medical_specialty ,Hereditary cancer and cancer-related syndromes Genetics and epigenetic pathways of disease [ONCOL 1] ,Population ,Single-nucleotide polymorphism ,Biology ,Ovarian Neoplasms - genetics ,Polymorphism, Single Nucleotide ,Article ,Càncer de mama ,03 medical and health sciences ,Germline mutation ,SDG 3 - Good Health and Well-being ,Translational research [ONCOL 3] ,Ovarian cancer ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,ddc:610 ,Genetics and epigenetic pathways of disease Translational research [NCMLS 6] ,education ,Retrospective Studies ,030304 developmental biology ,BRCA2 Protein ,Hereditary cancer and cancer-related syndromes [ONCOL 1] ,association ,Retrospective cohort study ,snp ,Odds ratio ,BRCA1 Protein - genetics ,medicine.disease ,BRCA2 Protein - genetics ,Mutation - Abstract
Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 x 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 x 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 x 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer., link_to_OA_fulltext
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- 2012
21. Association of Type and Location ofBRCA1andBRCA2Mutations With Risk of Breast and Ovarian Cancer
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Rebbeck, Timothy R., primary, Mitra, Nandita, additional, Wan, Fei, additional, Sinilnikova, Olga M., additional, Healey, Sue, additional, McGuffog, Lesley, additional, Mazoyer, Sylvie, additional, Chenevix-Trench, Georgia, additional, Easton, Douglas F., additional, Antoniou, Antonis C., additional, Nathanson, Katherine L., additional, Laitman, Yael, additional, Kushnir, Anya, additional, Paluch-Shimon, Shani, additional, Berger, Raanan, additional, Zidan, Jamal, additional, Friedman, Eitan, additional, Ehrencrona, Hans, additional, Stenmark-Askmalm, Marie, additional, Einbeigi, Zakaria, additional, Loman, Niklas, additional, Harbst, Katja, additional, Rantala, Johanna, additional, Melin, Beatrice, additional, Huo, Dezheng, additional, Olopade, Olufunmilayo I., additional, Seldon, Joyce, additional, Ganz, Patricia A., additional, Nussbaum, Robert L., additional, Chan, Salina B., additional, Odunsi, Kunle, additional, Gayther, Simon A., additional, Domchek, Susan M., additional, Arun, Banu K., additional, Lu, Karen H., additional, Mitchell, Gillian, additional, Karlan, Beth Y., additional, Walsh, Christine, additional, Lester, Jenny, additional, Godwin, Andrew K., additional, Pathak, Harsh, additional, Ross, Eric, additional, Daly, Mary B., additional, Whittemore, Alice S., additional, John, Esther M., additional, Miron, Alexander, additional, Terry, Mary Beth, additional, Chung, Wendy K., additional, Goldgar, David E., additional, Buys, Saundra S., additional, Janavicius, Ramunas, additional, Tihomirova, Laima, additional, Tung, Nadine, additional, Dorfling, Cecilia M., additional, van Rensburg, Elizabeth J., additional, Steele, Linda, additional, Neuhausen, Susan L., additional, Ding, Yuan Chun, additional, Ejlertsen, Bent, additional, Gerdes, Anne-Marie, additional, Hansen, Thomas v. O., additional, Ramón y Cajal, Teresa, additional, Osorio, Ana, additional, Benitez, Javier, additional, Godino, Javier, additional, Tejada, Maria-Isabel, additional, Duran, Mercedes, additional, Weitzel, Jeffrey N., additional, Bobolis, Kristie A, additional, Sand, Sharon R., additional, Fontaine, Annette, additional, Savarese, Antonella, additional, Pasini, Barbara, additional, Peissel, Bernard, additional, Bonanni, Bernardo, additional, Zaffaroni, Daniela, additional, Vignolo-Lutati, Francesca, additional, Scuvera, Giulietta, additional, Giannini, Giuseppe, additional, Bernard, Loris, additional, Genuardi, Maurizio, additional, Radice, Paolo, additional, Dolcetti, Riccardo, additional, Manoukian, Siranoush, additional, Pensotti, Valeria, additional, Gismondi, Viviana, additional, Yannoukakos, Drakoulis, additional, Fostira, Florentia, additional, Garber, Judy, additional, Torres, Diana, additional, Rashid, Muhammad Usman, additional, Hamann, Ute, additional, Peock, Susan, additional, Frost, Debra, additional, Platte, Radka, additional, Evans, D. Gareth, additional, Eeles, Rosalind, additional, Davidson, Rosemarie, additional, Eccles, Diana, additional, Cole, Trevor, additional, Cook, Jackie, additional, Brewer, Carole, additional, Hodgson, Shirley, additional, Morrison, Patrick J., additional, Walker, Lisa, additional, Porteous, Mary E., additional, Kennedy, M. John, additional, Izatt, Louise, additional, Adlard, Julian, additional, Donaldson, Alan, additional, Ellis, Steve, additional, Sharma, Priyanka, additional, Schmutzler, Rita Katharina, additional, Wappenschmidt, Barbara, additional, Becker, Alexandra, additional, Rhiem, Kerstin, additional, Hahnen, Eric, additional, Engel, Christoph, additional, Meindl, Alfons, additional, Engert, Stefanie, additional, Ditsch, Nina, additional, Arnold, Norbert, additional, Plendl, Hans Jörg, additional, Mundhenke, Christoph, additional, Niederacher, Dieter, additional, Fleisch, Markus, additional, Sutter, Christian, additional, Bartram, C. R., additional, Dikow, Nicola, additional, Wang-Gohrke, Shan, additional, Gadzicki, Dorothea, additional, Steinemann, Doris, additional, Kast, Karin, additional, Beer, Marit, additional, Varon-Mateeva, Raymonda, additional, Gehrig, Andrea, additional, Weber, Bernhard H., additional, Stoppa-Lyonnet, Dominique, additional, Houdayer, Claude, additional, Belotti, Muriel, additional, Gauthier-Villars, Marion, additional, Damiola, Francesca, additional, Boutry-Kryza, Nadia, additional, Lasset, Christine, additional, Sobol, Hagay, additional, Peyrat, Jean-Philippe, additional, Muller, Danièle, additional, Fricker, Jean-Pierre, additional, Collonge-Rame, Marie-Agnès, additional, Mortemousque, Isabelle, additional, Nogues, Catherine, additional, Rouleau, Etienne, additional, Isaacs, Claudine, additional, De Paepe, Anne, additional, Poppe, Bruce, additional, Claes, Kathleen, additional, De Leeneer, Kim, additional, Piedmonte, Marion, additional, Rodriguez, Gustavo, additional, Wakely, Katie, additional, Boggess, John, additional, Blank, Stephanie V., additional, Basil, Jack, additional, Azodi, Masoud, additional, Phillips, Kelly-Anne, additional, Caldes, Trinidad, additional, de la Hoya, Miguel, additional, Romero, Atocha, additional, Nevanlinna, Heli, additional, Aittomäki, Kristiina, additional, van der Hout, Annemarie H., additional, Hogervorst, Frans B. L., additional, Verhoef, Senno, additional, Collée, J. Margriet, additional, Seynaeve, Caroline, additional, Oosterwijk, Jan C., additional, Gille, Johannes J. P., additional, Wijnen, Juul T., additional, Garcia, Encarna B. Gómez, additional, Kets, Carolien M., additional, Ausems, Margreet G. E. M., additional, Aalfs, Cora M., additional, Devilee, Peter, additional, Mensenkamp, Arjen R., additional, Kwong, Ava, additional, Olah, Edith, additional, Papp, Janos, additional, Diez, Orland, additional, Lazaro, Conxi, additional, Darder, Esther, additional, Blanco, Ignacio, additional, Salinas, Mónica, additional, Jakubowska, Anna, additional, Lubinski, Jan, additional, Gronwald, Jacek, additional, Jaworska-Bieniek, Katarzyna, additional, Durda, Katarzyna, additional, Sukiennicki, Grzegorz, additional, Huzarski, Tomasz, additional, Byrski, Tomasz, additional, Cybulski, Cezary, additional, Toloczko-Grabarek, Aleksandra, additional, Zlowocka-Perlowska, Elzbieta, additional, Menkiszak, Janusz, additional, Arason, Adalgeir, additional, Barkardottir, Rosa B., additional, Simard, Jacques, additional, Laframboise, Rachel, additional, Montagna, Marco, additional, Agata, Simona, additional, Alducci, Elisa, additional, Peixoto, Ana, additional, Teixeira, Manuel R., additional, Spurdle, Amanda B., additional, Lee, Min Hyuk, additional, Park, Sue K., additional, Kim, Sung-Won, additional, Friebel, Tara M., additional, Couch, Fergus J., additional, Lindor, Noralane M., additional, Pankratz, Vernon S., additional, Guidugli, Lucia, additional, Wang, Xianshu, additional, Tischkowitz, Marc, additional, Foretova, Lenka, additional, Vijai, Joseph, additional, Offit, Kenneth, additional, Robson, Mark, additional, Rau-Murthy, Rohini, additional, Kauff, Noah, additional, Fink-Retter, Anneliese, additional, Singer, Christian F., additional, Rappaport, Christine, additional, Gschwantler-Kaulich, Daphne, additional, Pfeiler, Georg, additional, Tea, Muy-Kheng, additional, Berger, Andreas, additional, Greene, Mark H., additional, Mai, Phuong L., additional, Imyanitov, Evgeny N., additional, Toland, Amanda Ewart, additional, Senter, Leigha, additional, Bojesen, Anders, additional, Pedersen, Inge Sokilde, additional, Skytte, Anne-Bine, additional, Sunde, Lone, additional, Thomassen, Mads, additional, Moeller, Sanne Traasdahl, additional, Kruse, Torben A., additional, Jensen, Uffe Birk, additional, Caligo, Maria Adelaide, additional, Aretini, Paolo, additional, Teo, Soo-Hwang, additional, Selkirk, Christina G., additional, Hulick, Peter J., additional, and Andrulis, Irene, additional
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- 2015
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22. Colour Doppler ultrasound in preoperative assessment of the neck vessels in patients with tumours of the oral cavity and the neck region
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Aleksander, Falkowski, Grazyna, Wilk, Stanisław, Mokrzyński, Przemysław, Dul, Aleksandra, Toloczko-Grabarek, Tomasz, Huzarski, and Robert, Kowalczyk
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Adult ,Aged, 80 and over ,Male ,Adolescent ,Middle Aged ,Prognosis ,Salivary Gland Neoplasms ,Young Adult ,Head and Neck Neoplasms ,Lymphatic Metastasis ,Preoperative Care ,Humans ,Carotid Stenosis ,Female ,Mouth Neoplasms ,Jugular Veins ,Ultrasonography, Doppler, Color ,Neck ,Aged - Abstract
The aim of the study was not only to establish the applicability of color Doppler ultrasound of the neck vessels in patients with tumors of the oral cavity and the neck region but also to check whether the coexistence of sclerotic changes in the carotid arteries is essential in determination of the sequence of surgical procedure.Color Doppler ultrasound was performed on 110 patients, aged 15 -71 years with tumors of the oral cavity and the neck. The localization, size, echogenicity, as well as the tumor relationship to the surrounding structures and big vessels of the neck region was analyzed.Compression of the veins was observed in 27 cases, and of the arteries only in 20 cases. Infiltration of the jugular vein was observed in 8 patients, whereas infiltration of the carotid artery were seen only in 6 patients. Severe internal carotid artery stenosis, due to arteriosclerosis, was observed in 10 patients. Three persons were suggested to be operated on, first due to carotid artery stenosis, later on, due to the oral cavity tumor.It was found that color Doppler ultrasound is useful in deciding upon the method of treatment, while the examination of the neck vessels is helpful in establishing the sequence of surgical procedures in patients with tumors and coexisting arteriosclerosis.
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- 2004
23. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer
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Bojesen, Stig E., Pooley, Karen A., Johnatty, Sharon E., Beesley, Jonathan, Michailidou, Kyriaki, Tyrer, Jonathan P., Edwards, Stacey L., Pickett, Hilda A., Shen, Howard C., Smart, Chanel E., Hillman, Kristine M., Mai, Phuong L., Lawrenson, Kate, Stutz, Michael D., Lu, Yi, Karevan, Rod, Woods, Nicholas, Johnstonw, Rebecca L., French, Juliet D., Chen, Xiaoqing, Weischer, Maren, Nielsen, Sune F., Maranian, Melanie J., Ghoussaini, Maya, Ahmed, Shahana, Baynes, Caroline, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, McGuffog, Lesley, Barrowdale, Daniel, Lee, Andrew, Healey, Sue, Lush, Michael, Tessier, Daniel C., Vincent, Daniel, Bacot, Francis, Vergote, Ignace, Lambrechts, Sandrina, Despierre, Evelyn, Risch, Harvey A., Gonzalez-Neira, Anna, Rossing, Mary Anne, Pita, Guillermo, Doherty, Jennifer A., Alvarez, Nuria, Larson, Melissa C., Fridley, Brooke L., Schoof, Nils, Chang-Claude, Jenny, Cicek, Mine S., Peto, Julian, Kalli, Kimberly R., Broeks, Annegien, Armasu, Sebastian M., Schmidt, Marjanka K., Braaf, Linde M., Winterhoff, Boris, Nevanlinna, Heli, Konecny, Gottfried E., Lambrechts, Diether, Rogmann, Lisa, Guenel, Pascal, Teoman, Attila, Milne, Roger L., Garcia, Joaquin J., Cox, Angela, Shridhar, Vijayalakshmi, Burwinkel, Barbara, Marme, Frederik, Hein, Rebecca, Sawyer, Elinor J., Haiman, Christopher A., Wang-Gohrke, Shan, Andrulis, Irene L., Moysich, Kirsten B., Hopper, John L., Odunsi, Kunle, Lindblom, Annika, Giles, Graham G., Brenner, Hermann, Simard, Jacques, Lurie, Galina, Fasching, Peter A., Carney, Michael E., Radice, Paolo, Wilkens, Lynne R., Swerdlow, Anthony, Goodman, Marc T., Brauch, Hiltrud, Garcia-Closas, Montserrat, Hillemanns, Peter, Winqvist, Robert, Durst, Matthias, Devilee, Peter, Runnebaum, Ingo, Jakubowska, Anna, Lubinski, Jan, Mannermaa, Arto, Butzow, Ralf, Bogdanova, Natalia V., Doerk, Thilo, Pelttari, Liisa M., Zheng, Wei, Leminen, Arto, Anton-Culver, Hoda, Bunker, Clareann H., Kristensen, Vessela, Ness, Roberta B., Muir, Kenneth, Edwards, Robert, Meindl, Alfons, Heitz, Florian, Matsuo, Keitaro, du Bois, Andreas, Wu, Anna H., Harter, Philipp, Teo, Soo-Hwang, Schwaab, Ira, Shu, Xiao-Ou, Blot, William, Hosono, Satoyo, Kang, Daehee, Nakanishi, Toru, Hartman, Mikael, Yatabe, Yasushi, Hamann, Ute, Karlan, Beth Y., Sangrajrang, Suleeporn, Kjaer, Susanne Kruger, Gaborieau, Valerie, Jensen, Allan, Eccles, Diana, Hogdall, Estrid, Shen, Chen-Yang, Brown, Judith, Woo, Yin Ling, Shah, Mitul, Azmi, Mat Adenan Noor, Luben, Robert, Omar, Siti Zawiah, Czene, Kamila, Vierkant, Robert A., Nordestgaard, Borge G., Flyger, Henrik, Vachon, Celine, Olson, Janet E., Wang, Xianshu, Levine, Douglas A., Rudolph, Anja, Weber, Rachel Palmieri, Flesch-Janys, Dieter, Iversen, Edwin, Nickels, Stefan, Schildkraut, Joellen M., Silva, Isabel Dos Santos, Cramer, Daniel W., Gibson, Lorna, Terry, Kathryn L., Fletcher, Olivia, Vitonis, Allison F., van der Schoot, C. Ellen, Poole, Elizabeth M., Hogervorst, Frans B. L., Tworoger, Shelley S., Liu, Jianjun, Bandera, Elisa V., Li, Jingmei, Olson, Sara H., Humphreys, Keith, Row, Irene, Blomqvist, Carl, Rodriguez-Rodriguez, Lorna, Aittomaki, Kristiina, Salvesen, Helga B., Muranen, Taru A., Wik, Elisabeth, Brouwers, Barbara, Krakstad, Camilla, Wauters, Els, Halle, Mari K., Wildiers, Hans, Kiemeney, Lambertus A., Mulot, Claire, Aben, Katja K., Laurent-Puig, Pierre, Altena, Anne Mvan, Truong, Therese, Massuger, Leon F. A. G., Benitez, Javier, Pejovic, Tanja, Arias Perez, Jose Ignacio, Hoatlin, Maureen, Zamora, M. Pilar, Cook, Linda S., Balasubramanian, Sabapathy P., Kelemen, Linda E., Schneeweiss, Andreas, Le, Nhu D., Sohn, Christof, Brooks-Wilson, Angela, Tomlinson, Ian, Kerin, Michael J., Miller, Nicola, Cybulski, Cezary, Henderson, Brian E., Menkiszak, Janusz, Schumacher, Fredrick, Wentzensen, Nicolas, Marchand, Loic Le, Yang, Hannah P., Mulligan, Anna Marie, Glendon, Gord, Engelholm, Svend Aage, Knight, Julia A., Hogdall, Claus K., Apicella, Carmel, Gore, Martin, Tsimiklis, Helen, Song, Honglin, Southey, Melissa C., Jager, Agnes, den Ouweland, Ans M. Wvan, Brown, Robert, Martens, John W. M., Flanagan, James M., Kriege, Mieke, Paul, James, Margolin, Sara, Siddiqui, Nadeem, Severi, Gianluca, Whittemore, Alice S., Baglietto, Laura, McGuire, Valerie, Stegmaier, Christa, Sieh, Weiva, Mueller, Heiko, Arndt, Volker, Labreche, France, Gao, Yu-Tang, Goldberg, Mark S., Yang, Gong, Dumont, Martine, McLaughlin, John R., Hartmann, Arndt, Ekici, Arif B., Beckmann, Matthias W., Phelan, Catherine M., Lux, Michael P., Permuth-Wey, Jenny, Peissel, Bernard, Sellers, Thomas A., Ficarazzi, Filomena, Barile, Monica, Ziogas, Argyrios, Ashworth, Alan, Gentry-Maharaj, Aleksandra, Jones, Michael, Ramus, Susan J., Orr, Nick, Menon, Usha, Pearce, Celeste L., Bruening, Thomas, Pike, Malcolm C., Ko, Yon-Dschun, Lissowska, Jolanta, Figueroa, Jonine, Kupryjanczyk, Jolanta, Chanock, Stephen J., Dansonka-Mieszkowska, Agnieszka, Jukkola-Vuorinen, Arja, Rzepecka, Iwona K., Pylkas, Katri, Bidzinski, Mariusz, Kauppila, Saila, Hollestelle, Antoinette, Seynaeve, Caroline, Tollenaar, Rob A. E. M., Durda, Katarzyna, Jaworska, Katarzyna, Hartikainen, Jaana M., Kosma, Veli-Matti, Kataja, Vesa, Antonenkova, Natalia N., Long, Jirong, Shrubsole, Martha, Deming-Halverson, Sandra, Lophatananon, Artitaya, Siriwanarangsan, Pornthep, Stewart-Brown, Sarah, Ditsch, Nina, Lichtner, Peter, Schmutzler, Rita K., Ito, Hidemi, Iwata, Hiroji, Tajima, Kazuo, Tseng, Chiu-Chen, Stram, Daniel O., van den Berg, David, Yip, Cheng Har, Ikrarn, M. Kamran, Teh, Yew-Ching, Cai, Hui, Lu, Wei, Signorello, Lisa B., Cai, Qiuyin, Noh, Dong-Young, Yoo, Keun-Young, Miao, Hui, Iau, Philip Tsau-Choong, Teo, Yik Ying, McKay, James, Shapiro, Charles, Ademuyiwa, Foluso, Fountzilas, George, Hsiung, Chia-Ni, Yu, Jyh-Cherng, Hou, Ming-Feng, Healey, Catherine S., Luccarini, Craig, Peock, Susan, Stoppa-Lyonnet, Dominique, Peterlongo, Paolo, Rebbeck, Timothy R., Piedmonte, Marion, Singer, Christian F., Friedman, Eitan, Thomassen, Mads, Offit, Kenneth, Hansen, Thomas V. O., Neuhausen, Susan L., Szabo, Csilla I., Blanco, Ignacio, Garber, Judy, Narod, Steven A., Weitzel, Jeffrey N., Montagna, Marco, Olah, Edith, Godwin, Andrew K., Yannoukakos, Drakoulis, Goldgar, David E., Caldes, Trinidad, Imyanitov, Evgeny N., Tihomirova, Laima, Arun, Banu K., Campbell, Ian, Mensenkamp, Arjen R., van Asperen, Christi J., van Roozendaa, Kees E. P., Meijers-Heijboer, Hanne, Collee, J. Margriet, Oosterwijk, Jan C., Hooning, Maartje J., Rookus, Matti A., van der Luijt, Rob B., Os, Theo A. Mvan, Evans, D. Gareth, Frost, Debra, Fineberg, Elena, Barwell, Julian, Walker, Lisa, Kennedy, M. John, Platte, Radka, Davidson, Rosemarie, Ellis, Steve D., Cole, Trevor, Bressac-de Paillerets, Brigitte, Buecher, Bruno, Damiola, Francesca, Faivre, Laurence, Frenay, Marc, Sinilnikova, Olga M., Caron, Olivier, Giraud, Sophie, Mazoyer, Sylvie, Bonadona, Valerie, Caux-Moncoutier, Virginie, Toloczko-Grabarek, Aleksandra, Gronwald, Jacek, Byrski, Tomasz, Spurdle, Amanda B., Bonanni, Bernardo, Zaffaroni, Daniela, Giannini, Giuseppe, Bernard, Loris, Dolcetti, Riccardo, Manoukian, Siranoush, Arnold, Norbert, Engel, Christoph, Deissler, Helmut, Rhiem, Kerstin, Niederacher, Dieter, Pendl, Hansjoerg, Sutter, Christian, Wappenschmidt, Barbara, Borg, Ake, Mein, Beatrice, Rantala, Johanna, Soller, Maria, Nathanson, Katherine L., Domchek, Susan M., Rodriguez, Gustavo C., Salani, Ritu, Kaulich, Daphne Gschwantler, Tea, Muy-Kheng, Paluch, Shani Shimon, Laitman, Yael, Skytte, Anne-Bine, Kruse, Torben A., Jensen, Uffe Birk, Robson, Mark, Gerdes, Anne-Marie, Ejlertsen, Bent, Foretova, Lenka, Savage, Sharon A., Lesterm, Jenny, Soucy, Penny, Kuchenbaecker, Karoline B., Olswold, Curtis, Cunningham, Julie M., Slager, Susan, Pankratz, Vernon S., Dicks, Ed, Lakhani, Sunil R., Couch, Fergus J., Hall, Per, Monteiro, Alvaro N. A., Gayther, Simon A., Pharoah, Paul D. P., Reddel, Roger R., Goode, Ellen L., Greene, Mark H., Easton, Douglas F., Berchuck, Andrew, Antoniou, Antonis C., Chenevix-Trench, Georgia, Dunning, Alison M., Bojesen, Stig E., Pooley, Karen A., Johnatty, Sharon E., Beesley, Jonathan, Michailidou, Kyriaki, Tyrer, Jonathan P., Edwards, Stacey L., Pickett, Hilda A., Shen, Howard C., Smart, Chanel E., Hillman, Kristine M., Mai, Phuong L., Lawrenson, Kate, Stutz, Michael D., Lu, Yi, Karevan, Rod, Woods, Nicholas, Johnstonw, Rebecca L., French, Juliet D., Chen, Xiaoqing, Weischer, Maren, Nielsen, Sune F., Maranian, Melanie J., Ghoussaini, Maya, Ahmed, Shahana, Baynes, Caroline, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, McGuffog, Lesley, Barrowdale, Daniel, Lee, Andrew, Healey, Sue, Lush, Michael, Tessier, Daniel C., Vincent, Daniel, Bacot, Francis, Vergote, Ignace, Lambrechts, Sandrina, Despierre, Evelyn, Risch, Harvey A., Gonzalez-Neira, Anna, Rossing, Mary Anne, Pita, Guillermo, Doherty, Jennifer A., Alvarez, Nuria, Larson, Melissa C., Fridley, Brooke L., Schoof, Nils, Chang-Claude, Jenny, Cicek, Mine S., Peto, Julian, Kalli, Kimberly R., Broeks, Annegien, Armasu, Sebastian M., Schmidt, Marjanka K., Braaf, Linde M., Winterhoff, Boris, Nevanlinna, Heli, Konecny, Gottfried E., Lambrechts, Diether, Rogmann, Lisa, Guenel, Pascal, Teoman, Attila, Milne, Roger L., Garcia, Joaquin J., Cox, Angela, Shridhar, Vijayalakshmi, Burwinkel, Barbara, Marme, Frederik, Hein, Rebecca, Sawyer, Elinor J., Haiman, Christopher A., Wang-Gohrke, Shan, Andrulis, Irene L., Moysich, Kirsten B., Hopper, John L., Odunsi, Kunle, Lindblom, Annika, Giles, Graham G., Brenner, Hermann, Simard, Jacques, Lurie, Galina, Fasching, Peter A., Carney, Michael E., Radice, Paolo, Wilkens, Lynne R., Swerdlow, Anthony, Goodman, Marc T., Brauch, Hiltrud, Garcia-Closas, Montserrat, Hillemanns, Peter, Winqvist, Robert, Durst, Matthias, Devilee, Peter, Runnebaum, Ingo, Jakubowska, Anna, Lubinski, Jan, Mannermaa, Arto, Butzow, Ralf, Bogdanova, Natalia V., Doerk, Thilo, Pelttari, Liisa M., Zheng, Wei, Leminen, Arto, Anton-Culver, Hoda, Bunker, Clareann H., Kristensen, Vessela, Ness, Roberta B., Muir, Kenneth, Edwards, Robert, Meindl, Alfons, Heitz, Florian, Matsuo, Keitaro, du Bois, Andreas, Wu, Anna H., Harter, Philipp, Teo, Soo-Hwang, Schwaab, Ira, Shu, Xiao-Ou, Blot, William, Hosono, Satoyo, Kang, Daehee, Nakanishi, Toru, Hartman, Mikael, Yatabe, Yasushi, Hamann, Ute, Karlan, Beth Y., Sangrajrang, Suleeporn, Kjaer, Susanne Kruger, Gaborieau, Valerie, Jensen, Allan, Eccles, Diana, Hogdall, Estrid, Shen, Chen-Yang, Brown, Judith, Woo, Yin Ling, Shah, Mitul, Azmi, Mat Adenan Noor, Luben, Robert, Omar, Siti Zawiah, Czene, Kamila, Vierkant, Robert A., Nordestgaard, Borge G., Flyger, Henrik, Vachon, Celine, Olson, Janet E., Wang, Xianshu, Levine, Douglas A., Rudolph, Anja, Weber, Rachel Palmieri, Flesch-Janys, Dieter, Iversen, Edwin, Nickels, Stefan, Schildkraut, Joellen M., Silva, Isabel Dos Santos, Cramer, Daniel W., Gibson, Lorna, Terry, Kathryn L., Fletcher, Olivia, Vitonis, Allison F., van der Schoot, C. Ellen, Poole, Elizabeth M., Hogervorst, Frans B. L., Tworoger, Shelley S., Liu, Jianjun, Bandera, Elisa V., Li, Jingmei, Olson, Sara H., Humphreys, Keith, Row, Irene, Blomqvist, Carl, Rodriguez-Rodriguez, Lorna, Aittomaki, Kristiina, Salvesen, Helga B., Muranen, Taru A., Wik, Elisabeth, Brouwers, Barbara, Krakstad, Camilla, Wauters, Els, Halle, Mari K., Wildiers, Hans, Kiemeney, Lambertus A., Mulot, Claire, Aben, Katja K., Laurent-Puig, Pierre, Altena, Anne Mvan, Truong, Therese, Massuger, Leon F. A. G., Benitez, Javier, Pejovic, Tanja, Arias Perez, Jose Ignacio, Hoatlin, Maureen, Zamora, M. Pilar, Cook, Linda S., Balasubramanian, Sabapathy P., Kelemen, Linda E., Schneeweiss, Andreas, Le, Nhu D., Sohn, Christof, Brooks-Wilson, Angela, Tomlinson, Ian, Kerin, Michael J., Miller, Nicola, Cybulski, Cezary, Henderson, Brian E., Menkiszak, Janusz, Schumacher, Fredrick, Wentzensen, Nicolas, Marchand, Loic Le, Yang, Hannah P., Mulligan, Anna Marie, Glendon, Gord, Engelholm, Svend Aage, Knight, Julia A., Hogdall, Claus K., Apicella, Carmel, Gore, Martin, Tsimiklis, Helen, Song, Honglin, Southey, Melissa C., Jager, Agnes, den Ouweland, Ans M. Wvan, Brown, Robert, Martens, John W. M., Flanagan, James M., Kriege, Mieke, Paul, James, Margolin, Sara, Siddiqui, Nadeem, Severi, Gianluca, Whittemore, Alice S., Baglietto, Laura, McGuire, Valerie, Stegmaier, Christa, Sieh, Weiva, Mueller, Heiko, Arndt, Volker, Labreche, France, Gao, Yu-Tang, Goldberg, Mark S., Yang, Gong, Dumont, Martine, McLaughlin, John R., Hartmann, Arndt, Ekici, Arif B., Beckmann, Matthias W., Phelan, Catherine M., Lux, Michael P., Permuth-Wey, Jenny, Peissel, Bernard, Sellers, Thomas A., Ficarazzi, Filomena, Barile, Monica, Ziogas, Argyrios, Ashworth, Alan, Gentry-Maharaj, Aleksandra, Jones, Michael, Ramus, Susan J., Orr, Nick, Menon, Usha, Pearce, Celeste L., Bruening, Thomas, Pike, Malcolm C., Ko, Yon-Dschun, Lissowska, Jolanta, Figueroa, Jonine, Kupryjanczyk, Jolanta, Chanock, Stephen J., Dansonka-Mieszkowska, Agnieszka, Jukkola-Vuorinen, Arja, Rzepecka, Iwona K., Pylkas, Katri, Bidzinski, Mariusz, Kauppila, Saila, Hollestelle, Antoinette, Seynaeve, Caroline, Tollenaar, Rob A. E. M., Durda, Katarzyna, Jaworska, Katarzyna, Hartikainen, Jaana M., Kosma, Veli-Matti, Kataja, Vesa, Antonenkova, Natalia N., Long, Jirong, Shrubsole, Martha, Deming-Halverson, Sandra, Lophatananon, Artitaya, Siriwanarangsan, Pornthep, Stewart-Brown, Sarah, Ditsch, Nina, Lichtner, Peter, Schmutzler, Rita K., Ito, Hidemi, Iwata, Hiroji, Tajima, Kazuo, Tseng, Chiu-Chen, Stram, Daniel O., van den Berg, David, Yip, Cheng Har, Ikrarn, M. Kamran, Teh, Yew-Ching, Cai, Hui, Lu, Wei, Signorello, Lisa B., Cai, Qiuyin, Noh, Dong-Young, Yoo, Keun-Young, Miao, Hui, Iau, Philip Tsau-Choong, Teo, Yik Ying, McKay, James, Shapiro, Charles, Ademuyiwa, Foluso, Fountzilas, George, Hsiung, Chia-Ni, Yu, Jyh-Cherng, Hou, Ming-Feng, Healey, Catherine S., Luccarini, Craig, Peock, Susan, Stoppa-Lyonnet, Dominique, Peterlongo, Paolo, Rebbeck, Timothy R., Piedmonte, Marion, Singer, Christian F., Friedman, Eitan, Thomassen, Mads, Offit, Kenneth, Hansen, Thomas V. O., Neuhausen, Susan L., Szabo, Csilla I., Blanco, Ignacio, Garber, Judy, Narod, Steven A., Weitzel, Jeffrey N., Montagna, Marco, Olah, Edith, Godwin, Andrew K., Yannoukakos, Drakoulis, Goldgar, David E., Caldes, Trinidad, Imyanitov, Evgeny N., Tihomirova, Laima, Arun, Banu K., Campbell, Ian, Mensenkamp, Arjen R., van Asperen, Christi J., van Roozendaa, Kees E. P., Meijers-Heijboer, Hanne, Collee, J. Margriet, Oosterwijk, Jan C., Hooning, Maartje J., Rookus, Matti A., van der Luijt, Rob B., Os, Theo A. Mvan, Evans, D. Gareth, Frost, Debra, Fineberg, Elena, Barwell, Julian, Walker, Lisa, Kennedy, M. John, Platte, Radka, Davidson, Rosemarie, Ellis, Steve D., Cole, Trevor, Bressac-de Paillerets, Brigitte, Buecher, Bruno, Damiola, Francesca, Faivre, Laurence, Frenay, Marc, Sinilnikova, Olga M., Caron, Olivier, Giraud, Sophie, Mazoyer, Sylvie, Bonadona, Valerie, Caux-Moncoutier, Virginie, Toloczko-Grabarek, Aleksandra, Gronwald, Jacek, Byrski, Tomasz, Spurdle, Amanda B., Bonanni, Bernardo, Zaffaroni, Daniela, Giannini, Giuseppe, Bernard, Loris, Dolcetti, Riccardo, Manoukian, Siranoush, Arnold, Norbert, Engel, Christoph, Deissler, Helmut, Rhiem, Kerstin, Niederacher, Dieter, Pendl, Hansjoerg, Sutter, Christian, Wappenschmidt, Barbara, Borg, Ake, Mein, Beatrice, Rantala, Johanna, Soller, Maria, Nathanson, Katherine L., Domchek, Susan M., Rodriguez, Gustavo C., Salani, Ritu, Kaulich, Daphne Gschwantler, Tea, Muy-Kheng, Paluch, Shani Shimon, Laitman, Yael, Skytte, Anne-Bine, Kruse, Torben A., Jensen, Uffe Birk, Robson, Mark, Gerdes, Anne-Marie, Ejlertsen, Bent, Foretova, Lenka, Savage, Sharon A., Lesterm, Jenny, Soucy, Penny, Kuchenbaecker, Karoline B., Olswold, Curtis, Cunningham, Julie M., Slager, Susan, Pankratz, Vernon S., Dicks, Ed, Lakhani, Sunil R., Couch, Fergus J., Hall, Per, Monteiro, Alvaro N. A., Gayther, Simon A., Pharoah, Paul D. P., Reddel, Roger R., Goode, Ellen L., Greene, Mark H., Easton, Douglas F., Berchuck, Andrew, Antoniou, Antonis C., Chenevix-Trench, Georgia, and Dunning, Alison M.
- Abstract
TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOG, we analyzed similar to 480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 x 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 x 10(-8)) and BRCA1 mutation carrier (P = 1.1 x 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 x 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 x 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 x 10(-12)) and BRCA1 mutation carrier (P = 1.6 x 10-14) breast and invasive ovarian (P = 1.3 x 10(-11)) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.
- Published
- 2013
- Full Text
- View/download PDF
24. Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.
- Author
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Ramus, Susan J, Antoniou, Antonis C, Kuchenbaecker, Karoline B, Soucy, Penny, Beesley, Jonathan, Chen, Xiaoqing, McGuffog, Lesley, Sinilnikova, Olga M, Healey, Sue, Barrowdale, Daniel, Lee, Andrew, Thomassen, Mads, Gerdes, Anne-Marie, Kruse, Torben A, Jensen, Uffe Birk, Skytte, Anne-Bine, Caligo, Maria A, Liljegren, Annelie, Lindblom, Annika, Olsson, Håkan, Kristoffersson, Ulf, Stenmark-Askmalm, Marie, Melin, Beatrice, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Jakubowska, Anna, Lubinski, Jan, Jaworska, Katarzyna, Durda, Katarzyna, Złowocka, Elżbieta, Gronwald, Jacek, Huzarski, Tomasz, Byrski, Tomasz, Cybulski, Cezary, Toloczko-Grabarek, Aleksandra, Osorio, Ana, Benitez, Javier, Duran, Mercedes, Tejada, Maria-Isabel, Hamann, Ute, Rookus, Matti, van Leeuwen, Flora E, Aalfs, Cora M, Meijers-Heijboer, Hanne E J, van Asperen, Christi J, van Roozendaal, K E P, Hoogerbrugge, Nicoline, Collée, J Margriet, Kriege, Mieke, van der Luijt, Rob B, Peock, Susan, Frost, Debra, Ellis, Steve D, Platte, Radka, Fineberg, Elena, Evans, D Gareth, Lalloo, Fiona, Jacobs, Chris, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Eccles, Diana, Cole, Trevor, Cook, Jackie, Paterson, Joan, Douglas, Fiona, Brewer, Carole, Hodgson, Shirley, Morrison, Patrick J, Walker, Lisa, Porteous, Mary E, Kennedy, M John, Pathak, Harsh, Godwin, Andrew K, Stoppa-Lyonnet, Dominique, Caux-Moncoutier, Virginie, de Pauw, Antoine, Gauthier-Villars, Marion, Mazoyer, Sylvie, Léoné, Mélanie, Calender, Alain, Lasset, Christine, Bonadona, Valérie, Hardouin, Agnès, Berthet, Pascaline, Bignon, Yves-Jean, Uhrhammer, Nancy, Faivre, Laurence, Loustalot, Catherine, Buys, Saundra, Daly, Mary, Miron, Alex, Terry, Mary Beth, Chung, Wendy K, John, Esther M, Southey, Melissa, Goldgar, David, Singer, Christian F, Tea, Muy-Kheng, Pfeiler, Georg, Fink-Retter, Anneliese, Hansen, Thomas v O, Ejlertsen, Bent, Johannsson, Oskar Th, Offit, Kenneth, Kirchhoff, Tomas, Gaudet, Mia M, Vijai, Joseph, Robson, Mark, Piedmonte, Marion, Phillips, Kelly-Anne, Van Le, Linda, Hoffman, James S, Ewart Toland, Amanda, Montagna, Marco, Tognazzo, Silvia, Imyanitov, Evgeny, Issacs, Claudine, Janavicius, Ramunas, Lazaro, Conxi, Blanco, Iganacio, Tornero, Eva, Navarro, Matilde, Moysich, Kirsten B, Karlan, Beth Y, Gross, Jenny, Olah, Edith, Vaszko, Tibor, Teo, Soo-Hwang, Ganz, Patricia A, Beattie, Mary S, Dorfling, Cecelia M, van Rensburg, Elizabeth J, Diez, Orland, Kwong, Ava, Schmutzler, Rita K, Wappenschmidt, Barbara, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Heidemann, Simone, Niederacher, Dieter, Preisler-Adams, Sabine, Gadzicki, Dorotehea, Varon-Mateeva, Raymonda, Deissler, Helmut, Gehrig, Andrea, Sutter, Christian, Kast, Karin, Fiebig, Britta, Schäfer, Dieter, Caldes, Trinidad, de la Hoya, Miguel, Nevanlinna, Heli, Aittomäki, Kristiina, Plante, Marie, Spurdle, Amanda B, Neuhausen, Susan L, Ding, Yuan Chun, Wang, Xianshu, Lindor, Noralane, Fredericksen, Zachary, Pankratz, V Shane, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Bonanni, Bernardo, Bernard, Loris, Dolcetti, Riccardo, Papi, Laura, Ottini, Laura, Radice, Paolo, Greene, Mark H, Mai, Phuong L, Andrulis, Irene L, Glendon, Gord, Ozcelik, Hilmi, Pharoah, Paul D P, Gayther, Simon A, Simard, Jacques, Easton, Douglas F, Couch, Fergus J, Chenevix-Trench, Georgia, Ramus, Susan J, Antoniou, Antonis C, Kuchenbaecker, Karoline B, Soucy, Penny, Beesley, Jonathan, Chen, Xiaoqing, McGuffog, Lesley, Sinilnikova, Olga M, Healey, Sue, Barrowdale, Daniel, Lee, Andrew, Thomassen, Mads, Gerdes, Anne-Marie, Kruse, Torben A, Jensen, Uffe Birk, Skytte, Anne-Bine, Caligo, Maria A, Liljegren, Annelie, Lindblom, Annika, Olsson, Håkan, Kristoffersson, Ulf, Stenmark-Askmalm, Marie, Melin, Beatrice, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Jakubowska, Anna, Lubinski, Jan, Jaworska, Katarzyna, Durda, Katarzyna, Złowocka, Elżbieta, Gronwald, Jacek, Huzarski, Tomasz, Byrski, Tomasz, Cybulski, Cezary, Toloczko-Grabarek, Aleksandra, Osorio, Ana, Benitez, Javier, Duran, Mercedes, Tejada, Maria-Isabel, Hamann, Ute, Rookus, Matti, van Leeuwen, Flora E, Aalfs, Cora M, Meijers-Heijboer, Hanne E J, van Asperen, Christi J, van Roozendaal, K E P, Hoogerbrugge, Nicoline, Collée, J Margriet, Kriege, Mieke, van der Luijt, Rob B, Peock, Susan, Frost, Debra, Ellis, Steve D, Platte, Radka, Fineberg, Elena, Evans, D Gareth, Lalloo, Fiona, Jacobs, Chris, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Eccles, Diana, Cole, Trevor, Cook, Jackie, Paterson, Joan, Douglas, Fiona, Brewer, Carole, Hodgson, Shirley, Morrison, Patrick J, Walker, Lisa, Porteous, Mary E, Kennedy, M John, Pathak, Harsh, Godwin, Andrew K, Stoppa-Lyonnet, Dominique, Caux-Moncoutier, Virginie, de Pauw, Antoine, Gauthier-Villars, Marion, Mazoyer, Sylvie, Léoné, Mélanie, Calender, Alain, Lasset, Christine, Bonadona, Valérie, Hardouin, Agnès, Berthet, Pascaline, Bignon, Yves-Jean, Uhrhammer, Nancy, Faivre, Laurence, Loustalot, Catherine, Buys, Saundra, Daly, Mary, Miron, Alex, Terry, Mary Beth, Chung, Wendy K, John, Esther M, Southey, Melissa, Goldgar, David, Singer, Christian F, Tea, Muy-Kheng, Pfeiler, Georg, Fink-Retter, Anneliese, Hansen, Thomas v O, Ejlertsen, Bent, Johannsson, Oskar Th, Offit, Kenneth, Kirchhoff, Tomas, Gaudet, Mia M, Vijai, Joseph, Robson, Mark, Piedmonte, Marion, Phillips, Kelly-Anne, Van Le, Linda, Hoffman, James S, Ewart Toland, Amanda, Montagna, Marco, Tognazzo, Silvia, Imyanitov, Evgeny, Issacs, Claudine, Janavicius, Ramunas, Lazaro, Conxi, Blanco, Iganacio, Tornero, Eva, Navarro, Matilde, Moysich, Kirsten B, Karlan, Beth Y, Gross, Jenny, Olah, Edith, Vaszko, Tibor, Teo, Soo-Hwang, Ganz, Patricia A, Beattie, Mary S, Dorfling, Cecelia M, van Rensburg, Elizabeth J, Diez, Orland, Kwong, Ava, Schmutzler, Rita K, Wappenschmidt, Barbara, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Heidemann, Simone, Niederacher, Dieter, Preisler-Adams, Sabine, Gadzicki, Dorotehea, Varon-Mateeva, Raymonda, Deissler, Helmut, Gehrig, Andrea, Sutter, Christian, Kast, Karin, Fiebig, Britta, Schäfer, Dieter, Caldes, Trinidad, de la Hoya, Miguel, Nevanlinna, Heli, Aittomäki, Kristiina, Plante, Marie, Spurdle, Amanda B, Neuhausen, Susan L, Ding, Yuan Chun, Wang, Xianshu, Lindor, Noralane, Fredericksen, Zachary, Pankratz, V Shane, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Bonanni, Bernardo, Bernard, Loris, Dolcetti, Riccardo, Papi, Laura, Ottini, Laura, Radice, Paolo, Greene, Mark H, Mai, Phuong L, Andrulis, Irene L, Glendon, Gord, Ozcelik, Hilmi, Pharoah, Paul D P, Gayther, Simon A, Simard, Jacques, Easton, Douglas F, Couch, Fergus J, and Chenevix-Trench, Georgia
- Abstract
Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 × 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 × 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 × 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer.
- Published
- 2012
- Full Text
- View/download PDF
25. Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers
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Ramus, S.J., Antoniou, A.C., Kuchenbaecker, K.B., Soucy, P., Beesley, J., Chen, X., McGuffog, L., Sinilnikova, O.M., Healey, S., Barrowdale, D., Lee, A., Thomassen, M., Gerdes, A.M., Kruse, T.A., Jensen, U.B., Skytte, A.B., Caligo, M.A., Liljegren, A., Lindblom, A., Olsson, H., Kristoffersson, U., Stenmark-Askmalm, M., Melin, B., Swe, B., Domchek, S.M., Nathanson, K.L., Rebbeck, T.R., Jakubowska, A., Lubinski, J., Jaworska, K., Durda, K., Zlowocka, E., Gronwald, J., Huzarski, T., Byrski, T., Cybulski, C., Toloczko-Grabarek, A., Osorio, A., Benitez, J., Duran, M., Tejada, M.I., Hamann, U., Rookus, M., van Leeuwen, F.E., Aalfs, C.M., Meijers-Heijboer, H.E., Asperen, C.J. van, van Roozendaal, K.E., Hoogerbrugge-van der Linden, N., Collee, J.M., Kriege, M., van der Luijt, R.B., Hebon, ., Embrace, ., Peock, S., Frost, D., Ellis, S.D., Platte, R., Fineberg, E., Evans, D.G., Lalloo, F., Jacobs, C, Eeles, R., Adlard, J., Davidson, R., Eccles, D., Cole, T., Cook, J.L., Paterson, J., Douglas, F., Brewer, C., Hodgson, S., Morrison, P.J., Walker, L., Porteous, M.E., Kennedy, M.J., Pathak, H., Godwin, A.K., Stoppa-Lyonnet, D., Caux-Moncoutier, V., de Pauw, A., Gauthier-Villars, M., Mazoyer, S., Leone, M., Calender, A., Lasset, C., Bonadona, V., Hardouin, A., Berthet, P., Bignon, Y.J., Uhrhammer, N., Faivre, L., Loustalot, C., Gemo, ., Buys, S., Daly, M., Miron, A., Terry, M.B., Chung, W.K., John, E.M., Ligtenberg, M.J., et al., Ramus, S.J., Antoniou, A.C., Kuchenbaecker, K.B., Soucy, P., Beesley, J., Chen, X., McGuffog, L., Sinilnikova, O.M., Healey, S., Barrowdale, D., Lee, A., Thomassen, M., Gerdes, A.M., Kruse, T.A., Jensen, U.B., Skytte, A.B., Caligo, M.A., Liljegren, A., Lindblom, A., Olsson, H., Kristoffersson, U., Stenmark-Askmalm, M., Melin, B., Swe, B., Domchek, S.M., Nathanson, K.L., Rebbeck, T.R., Jakubowska, A., Lubinski, J., Jaworska, K., Durda, K., Zlowocka, E., Gronwald, J., Huzarski, T., Byrski, T., Cybulski, C., Toloczko-Grabarek, A., Osorio, A., Benitez, J., Duran, M., Tejada, M.I., Hamann, U., Rookus, M., van Leeuwen, F.E., Aalfs, C.M., Meijers-Heijboer, H.E., Asperen, C.J. van, van Roozendaal, K.E., Hoogerbrugge-van der Linden, N., Collee, J.M., Kriege, M., van der Luijt, R.B., Hebon, ., Embrace, ., Peock, S., Frost, D., Ellis, S.D., Platte, R., Fineberg, E., Evans, D.G., Lalloo, F., Jacobs, C, Eeles, R., Adlard, J., Davidson, R., Eccles, D., Cole, T., Cook, J.L., Paterson, J., Douglas, F., Brewer, C., Hodgson, S., Morrison, P.J., Walker, L., Porteous, M.E., Kennedy, M.J., Pathak, H., Godwin, A.K., Stoppa-Lyonnet, D., Caux-Moncoutier, V., de Pauw, A., Gauthier-Villars, M., Mazoyer, S., Leone, M., Calender, A., Lasset, C., Bonadona, V., Hardouin, A., Berthet, P., Bignon, Y.J., Uhrhammer, N., Faivre, L., Loustalot, C., Gemo, ., Buys, S., Daly, M., Miron, A., Terry, M.B., Chung, W.K., John, E.M., Ligtenberg, M.J., and et al.
- Abstract
Item does not contain fulltext, Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 x 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 x 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 x 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer.
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- 2012
26. An evaluation of the polymorphisms Ins16bp and Arg72Pro in p53 as breast cancer risk modifiers in BRCA1 and BRCA2 mutation carriers.
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Osorio, A., Pollán, M., Pita, G., Schmutzler, R. K., Versmold, B., Engel, C., Meindl, A., Arnold, N., Preisler-Adams, S., Niederacher, D., Hofmann, W., Gadzicki, D., Jakubowska, A., Hamann, U., Lubinski, J., Toloczko-Grabarek, A., Cybulski, C., Debniak, T., Llort, G., and Yannoukakos, D.
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BREAST cancer ,PROLINE ,GENETIC polymorphisms ,P53 antioncogene ,GENES ,BREAST tumors ,COMPARATIVE studies ,DISEASE susceptibility ,RESEARCH methodology ,MEDICAL cooperation ,GENETIC mutation ,OVARIAN tumors ,PROTEINS ,RESEARCH ,RESEARCH funding ,EVALUATION research ,GENETIC carriers ,HAPLOTYPES ,GENOTYPES - Abstract
The close functional relationship between p53 and the breast cancer susceptibility genes BRCA1 and BRCA2 has promoted the investigation of various polymorphisms in the p53 gene as possible risk modifiers in BRCA1/2 mutation carriers. Specifically, two polymorphisms in p53, c.97-147ins16bp and p.Arg72Pro have been analysed as putative breast cancer susceptibility variants, and it has been recently reported that a p53 haplotype combining the absence of the 16-bp insertion and the presence of proline at codon 72 (No Ins-72Pro) was associated with an earlier age at the onset of the first primary tumour in BRCA2 mutation carriers in the Spanish population. In this study, we have evaluated this association in a series of 2932 BRCA1/2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. [ABSTRACT FROM AUTHOR]
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- 2008
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27. Breast cancer predisposing alleles in Poland.
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B. Grski, C. Cybulski, T. Huzarski, T. Byrski, J. Gronwald, A. Jakubowska, M. Stawicka, S. Gozdecka-Grodecka, M. Szwiec, K. Urbanski, J. Mitus, E. Marczyk, J. Dziuba, P. Wandzel, D. Surdyka, O. Haus, H. Janiszewska, T. Debniak, A. Toloczko-Grabarek, and K. Medrek
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BREAST cancer ,WOMEN'S health ,GENES ,BIOCHEMICAL genetics - Abstract
Summary Mutant alleles of several genes in the DNA repair pathway have been found to predispose women to breast cancer. From a public health perspective, the importance of a given allele in a population is determined by the frequency of the allele and by the relative risk of breast cancer that it confers. In Poland founder alleles of the BRCA1, CHEK2 and NBS1 genes have been associated with an increased risk of breast cancer, but the relative contribution of each of these alleles to the overall breast cancer burden has not yet been determined. We screened 2012 unselected cases of breast cancer and 4000 population controls for 7 different mutations in these genes. Overall, a mutation was found in 12% of the cases and in 6% of the controls. Mutations in BRCA1 and CHEK2 contributed in approximately equal measure to the burden of breast cancer in Poland. A BRCA1 mutation was present in 3% of the cases. The missense BRCA1 mutation C61G was associated with a higher odds ratio for breast cancer (OR=15) than were either of the truncating BRCA1 mutations 4153delA (OR=2.0) and 5382insC (OR=6.2). In contrast, a higher odds ratio was seen for truncating CHEK2 mutations (OR=2.1) than for the missense mutation I157T (OR=1.4). This study suggests that cancer risks may be specific for particular alleles of a susceptibility gene and that these different risks should be taken into account by genetic counselors. [ABSTRACT FROM AUTHOR]
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- 2005
28. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer
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Bojesen, Stig E, Pooley, Karen A, Johnatty, Sharon E, Beesley, Jonathan, Michailidou, Kyriaki, Tyrer, Jonathan P, Edwards, Stacey L, Pickett, Hilda A, Shen, Howard C, Smart, Chanel E, Hillman, Kristine M, Mai, Phuong L, Lawrenson, Kate, Stutz, Michael D, Lu, Yi, Karevan, Rod, Woods, Nicholas, Johnston, Rebecca L, French, Juliet D, Chen, Xiaoqing, Weischer, Maren, Nielsen, Sune F, Maranian, Melanie J, Ghoussaini, Maya, Ahmed, Shahana, Baynes, Caroline, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, McGuffog, Lesley, Barrowdale, Daniel, Lee, Andrew, Healey, Sue, Lush, Michael, Tessier, Daniel C, Vincent, Daniel, Bacot, Françis, Vergote, Ignace, Lambrechts, Sandrina, Despierre, Evelyn, Risch, Harvey A, González-Neira, Anna, Rossing, Mary Anne, Pita, Guillermo, Doherty, Jennifer A, Álvarez, Nuria, Larson, Melissa C, Fridley, Brooke L, Schoof, Nils, Chang-Claude, Jenny, Cicek, Mine S, Peto, Julian, Kalli, Kimberly R, Broeks, Annegien, Armasu, Sebastian M, Schmidt, Marjanka K, Braaf, Linde M, Winterhoff, Boris, Nevanlinna, Heli, Konecny, Gottfried E, Lambrechts, Diether, Rogmann, Lisa, Guénel, Pascal, Teoman, Attila, Milne, Roger L, Garcia, Joaquin J, Cox, Angela, Shridhar, Vijayalakshmi, Burwinkel, Barbara, Marme, Frederik, Hein, Rebecca, Sawyer, Elinor J, Haiman, Christopher A, Wang-Gohrke, Shan, Andrulis, Irene L, Moysich, Kirsten B, Hopper, John L, Odunsi, Kunle, Lindblom, Annika, Giles, Graham G, Brenner, Hermann, Simard, Jacques, Lurie, Galina, Fasching, Peter A, Carney, Michael E, Radice, Paolo, Wilkens, Lynne R, Swerdlow, Anthony, Goodman, Marc T, Brauch, Hiltrud, Garcia-Closas, Montserrat, Hillemanns, Peter, Winqvist, Robert, Dürst, Matthias, Devilee, Peter, Runnebaum, Ingo, Jakubowska, Anna, Lubinski, Jan, Mannermaa, Arto, Butzow, Ralf, Bogdanova, Natalia V, Dörk, Thilo, Pelttari, Liisa M, Zheng, Wei, Leminen, Arto, Anton-Culver, Hoda, Bunker, Clareann H, Kristensen, Vessela, Ness, Roberta B, Muir, Kenneth, Edwards, Robert, Meindl, Alfons, Heitz, Florian, Matsuo, Keitaro, du Bois, Andreas, Wu, Anna H, Harter, Philipp, Teo, Soo-Hwang, Schwaab, Ira, Shu, Xiao-Ou, Blot, William, Hosono, Satoyo, Kang, Daehee, Nakanishi, Toru, Hartman, Mikael, Yatabe, Yasushi, Hamann, Ute, Karlan, Beth Y, Sangrajrang, Suleeporn, Kjaer, Susanne Krüger, Gaborieau, Valerie, Jensen, Allan, Eccles, Diana, Høgdall, Estrid, Shen, Chen-Yang, Brown, Judith, Woo, Yin Ling, Shah, Mitul, Azmi, Mat Adenan Noor, Luben, Robert, Omar, Siti Zawiah, Czene, Kamila, Vierkant, Robert A, Nordestgaard, Børge G, Flyger, Henrik, Vachon, Celine, Olson, Janet E, Wang, Xianshu, Levine, Douglas A, Rudolph, Anja, Weber, Rachel Palmieri, Flesch-Janys, Dieter, Iversen, Edwin, Nickels, Stefan, Schildkraut, Joellen M, Silva, Isabel Dos Santos, Cramer, Daniel William, Gibson, Lorna, Terry, Kathryn Lynne, Fletcher, Olivia, Vitonis, Allison F, van der Schoot, C Ellen, Poole, Elizabeth M., Hogervorst, Frans B L, Tworoger, Shelley Slate, Liu, Jianjun, Bandera, Elisa V, Li, Jingmei, Olson, Sara H, Humphreys, Keith, Orlow, Irene, Blomqvist, Carl, Rodriguez-Rodriguez, Lorna, Aittomäki, Kristiina, Salvesen, Helga B, Muranen, Taru A, Wik, Elisabeth, Brouwers, Barbara, Krakstad, Camilla, Wauters, Els, Halle, Mari K, Wildiers, Hans, Kiemeney, Lambertus A, Mulot, Claire, Aben, Katja K, Laurent-Puig, Pierre, Altena, Anne Mvan, Truong, Thérèse, Massuger, Leon F A G, Benitez, Javier, Pejovic, Tanja, Perez, Jose Ignacio Arias, Hoatlin, Maureen, Zamora, M Pilar, Cook, Linda S, Balasubramanian, Sabapathy P, Kelemen, Linda E, Schneeweiss, Andreas, Le, Nhu D, Sohn, Christof, Brooks-Wilson, Angela, Tomlinson, Ian, Kerin, Michael J, Miller, Nicola, Cybulski, Cezary, Henderson, Brian E, Menkiszak, Janusz, Schumacher, Fredrick, Wentzensen, Nicolas, Le Marchand, Loic, Yang, Hannah P, Mulligan, Anna Marie, Glendon, Gord, Engelholm, Svend Aage, Knight, Julia A, Høgdall, Claus K, Apicella, Carmel, Gore, Martin, Tsimiklis, Helen, Song, Honglin, Southey, Melissa C, Jager, Agnes, den Ouweland, Ans M Wvan, Brown, Robert, Martens, John W M, Flanagan, James M, Kriege, Mieke, Paul, James, Margolin, Sara, Siddiqui, Nadeem, Severi, Gianluca, Whittemore, Alice S, Baglietto, Laura, McGuire, Valerie, Stegmaier, Christa, Sieh, Weiva, Müller, Heiko, Arndt, Volker, Labrèche, France, Gao, Yu-Tang, Goldberg, Mark S, Yang, Gong, Dumont, Martine, McLaughlin, John R, Hartmann, Arndt, Ekici, Arif B, Beckmann, Matthias W, Phelan, Catherine M, Lux, Michael P, Permuth-Wey, Jenny, Peissel, Bernard, Sellers, Thomas A, Ficarazzi, Filomena, Barile, Monica, Ziogas, Argyrios, Ashworth, Alan, Gentry-Maharaj, Aleksandra, Jones, Michael, Ramus, Susan J, Orr, Nick, Menon, Usha, Pearce, Celeste L, Brüning, Thomas, Pike, Malcolm C, Ko, Yon-Dschun, Lissowska, Jolanta, Figueroa, Jonine, Kupryjanczyk, Jolanta, Chanock, Stephen J, Dansonka-Mieszkowska, Agnieszka, Jukkola-Vuorinen, Arja, Rzepecka, Iwona K, Pylkäs, Katri, Bidzinski, Mariusz, Kauppila, Saila, Hollestelle, Antoinette, Seynaeve, Caroline, Tollenaar, Rob A E M, Durda, Katarzyna, Jaworska, Katarzyna, Hartikainen, Jaana M, Kosma, Veli-Matti, Kataja, Vesa, Antonenkova, Natalia N, Long, Jirong, Shrubsole, Martha, Deming-Halverson, Sandra, Lophatananon, Artitaya, Siriwanarangsan, Pornthep, Stewart-Brown, Sarah, Ditsch, Nina, Lichtner, Peter, Schmutzler, Rita K, Ito, Hidemi, Iwata, Hiroji, Tajima, Kazuo, Tseng, Chiu-Chen, Stram, Daniel O, van den Berg, David, Yip, Cheng Har, Ikram, M Kamran, Teh, Yew-Ching, Cai, Hui, Lu, Wei, Signorello, Lisa B, Cai, Qiuyin, Noh, Dong-Young, Yoo, Keun-Young, Miao, Hui, Iau, Philip Tsau-Choong, Teo, Yik Ying, McKay, James, Shapiro, Charles, Ademuyiwa, Foluso, Fountzilas, George, Hsiung, Chia-Ni, Yu, Jyh-Cherng, Hou, Ming-Feng, Healey, Catherine S, Luccarini, Craig, Peock, Susan, Stoppa-Lyonnet, Dominique, Peterlongo, Paolo, Rebbeck, Timothy R, Piedmonte, Marion, Singer, Christian F, Friedman, Eitan, Thomassen, Mads, Offit, Kenneth, Hansen, Thomas V O, Neuhausen, Susan L, Szabo, Csilla I, Blanco, Ignacio, Garber, Judy Ellen, Narod, Steven A, Weitzel, Jeffrey N, Montagna, Marco, Olah, Edith, Godwin, Andrew K, Yannoukakos, Drakoulis, Goldgar, David E, Caldes, Trinidad, Imyanitov, Evgeny N, Tihomirova, Laima, Arun, Banu K, Campbell, Ian, Mensenkamp, Arjen R, van Asperen, Christi J, van Roozendaal, Kees E P, Meijers-Heijboer, Hanne, Collée, J Margriet, Oosterwijk, Jan C, Hooning, Maartje J, Rookus, Matti A, van der Luijt, Rob B, Os, Theo A Mvan, Evans, D Gareth, Frost, Debra, Fineberg, Elena, Barwell, Julian, Walker, Lisa, Kennedy, M John, Platte, Radka, Davidson, Rosemarie, Ellis, Steve D, Cole, Trevor, Bressac-de Paillerets, Brigitte, Buecher, Bruno, Damiola, Francesca, Faivre, Laurence, Frenay, Marc, Sinilnikova, Olga M, Caron, Olivier, Giraud, Sophie, Mazoyer, Sylvie, Bonadona, Valérie, Caux-Moncoutier, Virginie, Toloczko-Grabarek, Aleksandra, Gronwald, Jacek, Byrski, Tomasz, Spurdle, Amanda B, Bonanni, Bernardo, Zaffaroni, Daniela, Giannini, Giuseppe, Bernard, Loris, Dolcetti, Riccardo, Manoukian, Siranoush, Arnold, Norbert, Engel, Christoph, Deissler, Helmut, Rhiem, Kerstin, Niederacher, Dieter, Plendl, Hansjoerg, Sutter, Christian, Wappenschmidt, Barbara, Borg, Åke, Melin, Beatrice, Rantala, Johanna, Soller, Maria, Nathanson, Katherine L, Domchek, Susan M, Rodriguez, Gustavo C, Salani, Ritu, Kaulich, Daphne Gschwantler, Tea, Muy-Kheng, Paluch, Shani Shimon, Laitman, Yael, Skytte, Anne-Bine, Kruse, Torben A, Jensen, Uffe Birk, Robson, Mark, Gerdes, Anne-Marie, Ejlertsen, Bent, Foretova, Lenka, Savage, Sharon A, Lester, Jenny, Soucy, Penny, Kuchenbaecker, Karoline B, Olswold, Curtis, Cunningham, Julie M, Slager, Susan, Pankratz, Vernon S, Dicks, Ed, Lakhani, Sunil R, Couch, Fergus J, Hall, Per, Monteiro, Alvaro N A, Gayther, Simon A, Pharoah, Paul D P, Reddel, Roger R, Goode, Ellen L, Greene, Mark H, Easton, Douglas F, Berchuck, Andrew, Antoniou, Antonis C, Chenevix-Trench, Georgia, and Dunning, Alison M
- Abstract
TERT-locus single nucleotide polymorphisms (SNPs) and leucocyte telomere measures are reportedly associated with risks of multiple cancers. Using the iCOGs chip, we analysed ~480 TERT-locus SNPs in breast (n=103,991), ovarian (n=39,774) and BRCA1 mutation carrier (11,705) cancer cases and controls. 53,724 participants have leucocyte telomere measures. Most associations cluster into three independent peaks. Peak 1 SNP rs2736108 minor allele associates with longer telomeres (P=5.8×10−7), reduced estrogen receptor negative (ER-negative) (P=1.0×10−8) and BRCA1 mutation carrier (P=1.1×10−5) breast cancer risks, and altered promoter-assay signal. Peak 2 SNP rs7705526 minor allele associates with longer telomeres (P=2.3×10−14), increased low malignant potential ovarian cancer risk (P=1.3×10−15) and increased promoter activity. Peak 3 SNPs rs10069690 and rs2242652 minor alleles increase ER-negative (P=1.2×10−12) and BRCA1 mutation carrier (P=1.6×10−14) breast and invasive ovarian (P=1.3×10−11) cancer risks, but not via altered telomere length. The cancer-risk alleles of rs2242652 and rs10069690 respectively increase silencing and generate a truncated TERT splice-variant.
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- 2013
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29. Population screening for cancer family syndromes in West-Pomeranian Region of Poland with 1.7 min inhabitants
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Lubinski, J, Raczynski, A, Tarhoni, M, Blachowski, M, Gronwald, J, Huzarski, T, Byrski, T, Toloczko-Grabarek, A, Debniak, T, and Cybulski, C
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- 2004
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30. Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women
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Rebbeck, TR, Friebel, TM, Mitra, N, Wan, F, Chen, S, Andrulis, IL, Apostolou, P, Arnold, N, Arun, BK, Barrowdale, D, Benitez, J, Berger, R, Berthet, P, Borg, A, Buys, SS, Caldes, T, Carter, J, Chiquette, J, Claes, KBM, Couch, FJ, Cybulski, C, Daly, MB, De La Hoya, M, Diez, O, Domchek, SM, Nathanson, KL, Durda, K, Ellis, S, EMBRACE, Evans, DG, Foretova, L, Friedman, E, Frost, D, Ganz, PA, Garber, J, Glendon, G, Godwin, AK, Greene, MH, Gronwald, J, Hahnen, E, Hallberg, E, Hamann, U, Hansen, TVO, HEBON, Imyanitov, EN, Isaacs, C, Jakubowska, A, Janavicius, R, Jaworska-Bieniek, K, John, EM, Karlan, BY, Kaufman, B, Investigators, K, Kwong, A, Laitman, Y, Lasset, C, Lazaro, C, Lester, J, Loman, N, Lubinski, J, Manoukian, S, Mitchell, G, Montagna, M, Neuhausen, SL, Nevanlinna, H, Niederacher, D, Nussbaum, RL, Offit, K, Olah, E, Olopade, OI, Park, SK, Piedmonte, M, Radice, P, Rappaport-Fuerhauser, C, Rookus, MA, Seynaeve, C, Simard, J, Singer, CF, Soucy, P, Southey, M, Stoppa-Lyonnet, D, Sukiennicki, G, Szabo, CI, Tancredi, M, Teixeira, MR, Teo, S-H, Terry, MB, Thomassen, M, Tihomirova, L, Tischkowitz, M, Toland, AE, Toloczko-Grabarek, A, Tung, N, Van Rensburg, EJ, Villano, D, Wang-Gohrke, S, Wappenschmidt, B, Weitzel, JN, Zidan, J, Zorn, KK, McGuffog, L, Easton, D, Chenevix-Trench, G, Antoniou, AC, and Ramus, SJ
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skin and connective tissue diseases ,BRCA1 ,hereditary breast and ovarian cancer ,BRCA2 ,transheterozygosity ,3. Good health - Abstract
Background: Most $\textit{BRCA1}$ or $\textit{BRCA2}$ mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both $\textit{BRCA1}$ and $\textit{BRCA2}$ are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female $\textit{BRCA1/2}$ mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at $\textit{BRCA1}$ (SH1) or $\textit{BRCA2}$ (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; $p$ = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 ($p$ = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 ($p$ = 0.231), but was on average 4.5 years younger in TH than in SH2 ($p$ < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive ($p$ = 0.010) or progesterone receptor (PR) positive ($p$ = 0.013) than in SH1, but less likely to be ER positive ($p$ < 0.001) or PR positive ($p$ = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for $\textit{BRCA1}$ or $\textit{BRCA2}$ in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2.
31. Colour Doppler ultrasound in preoperative assessment of the neck vessels in patients with tumours of the oral cavity and the neck region
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Falkowski, Aleksander, Grażyna Wilk, Mokrzynski, Stanislaw, Dul, Przemyslaw, Toloczko-Grabarek, Aleksandra, Huzarski, Tomasz, and Kowalczyk, Robert
32. Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.
- Author
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Ramus SJ, Antoniou AC, Kuchenbaecker KB, Soucy P, Beesley J, Chen X, McGuffog L, Sinilnikova OM, Healey S, Barrowdale D, Lee A, Thomassen M, Gerdes AM, Kruse TA, Jensen UB, Skytte AB, Caligo MA, Liljegren A, Lindblom A, Olsson H, Kristoffersson U, Stenmark-Askmalm M, Melin B, Domchek SM, Nathanson KL, Rebbeck TR, Jakubowska A, Lubinski J, Jaworska K, Durda K, Złowocka E, Gronwald J, Huzarski T, Byrski T, Cybulski C, Toloczko-Grabarek A, Osorio A, Benitez J, Duran M, Tejada MI, Hamann U, Rookus M, van Leeuwen FE, Aalfs CM, Meijers-Heijboer HE, van Asperen CJ, van Roozendaal KE, Hoogerbrugge N, Collée JM, Kriege M, van der Luijt RB, Peock S, Frost D, Ellis SD, Platte R, Fineberg E, Evans DG, Lalloo F, Jacobs C, Eeles R, Adlard J, Davidson R, Eccles D, Cole T, Cook J, Paterson J, Douglas F, Brewer C, Hodgson S, Morrison PJ, Walker L, Porteous ME, Kennedy MJ, Pathak H, Godwin AK, Stoppa-Lyonnet D, Caux-Moncoutier V, de Pauw A, Gauthier-Villars M, Mazoyer S, Léoné M, Calender A, Lasset C, Bonadona V, Hardouin A, Berthet P, Bignon YJ, Uhrhammer N, Faivre L, Loustalot C, Buys S, Daly M, Miron A, Terry MB, Chung WK, John EM, Southey M, Goldgar D, Singer CF, Tea MK, Pfeiler G, Fink-Retter A, Hansen Tv, Ejlertsen B, Johannsson OT, Offit K, Kirchhoff T, Gaudet MM, Vijai J, Robson M, Piedmonte M, Phillips KA, Van Le L, Hoffman JS, Ewart Toland A, Montagna M, Tognazzo S, Imyanitov E, Issacs C, Janavicius R, Lazaro C, Blanco I, Tornero E, Navarro M, Moysich KB, Karlan BY, Gross J, Olah E, Vaszko T, Teo SH, Ganz PA, Beattie MS, Dorfling CM, van Rensburg EJ, Diez O, Kwong A, Schmutzler RK, Wappenschmidt B, Engel C, Meindl A, Ditsch N, Arnold N, Heidemann S, Niederacher D, Preisler-Adams S, Gadzicki D, Varon-Mateeva R, Deissler H, Gehrig A, Sutter C, Kast K, Fiebig B, Schäfer D, Caldes T, de la Hoya M, Nevanlinna H, Aittomäki K, Plante M, Spurdle AB, Neuhausen SL, Ding YC, Wang X, Lindor N, Fredericksen Z, Pankratz VS, Peterlongo P, Manoukian S, Peissel B, Zaffaroni D, Bonanni B, Bernard L, Dolcetti R, Papi L, Ottini L, Radice P, Greene MH, Mai PL, Andrulis IL, Glendon G, Ozcelik H, Pharoah PD, Gayther SA, Simard J, Easton DF, Couch FJ, and Chenevix-Trench G
- Subjects
- Adult, Cohort Studies, Female, Genetic Predisposition to Disease, Heterozygote, Humans, Middle Aged, Odds Ratio, Retrospective Studies, BRCA1 Protein genetics, BRCA2 Protein genetics, Mutation, Ovarian Neoplasms genetics, Polymorphism, Single Nucleotide
- Abstract
Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 × 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 × 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 × 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer., (© 2012 Wiley Periodicals, Inc.)
- Published
- 2012
- Full Text
- View/download PDF
33. Colour Doppler ultrasound in preoperative assessment of the neck vessels in patients with tumours of the oral cavity and the neck region.
- Author
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Falkowski A, Wilk G, Mokrzyński S, Dul P, Toloczko-Grabarek A, Huzarski T, and Kowalczyk R
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Carotid Stenosis complications, Carotid Stenosis diagnostic imaging, Female, Head and Neck Neoplasms complications, Head and Neck Neoplasms surgery, Humans, Jugular Veins diagnostic imaging, Lymphatic Metastasis diagnostic imaging, Male, Middle Aged, Mouth Neoplasms complications, Mouth Neoplasms surgery, Neck blood supply, Neck diagnostic imaging, Preoperative Care, Prognosis, Salivary Gland Neoplasms blood supply, Salivary Gland Neoplasms complications, Salivary Gland Neoplasms diagnostic imaging, Salivary Gland Neoplasms surgery, Young Adult, Head and Neck Neoplasms blood supply, Head and Neck Neoplasms diagnostic imaging, Mouth Neoplasms blood supply, Mouth Neoplasms diagnostic imaging, Ultrasonography, Doppler, Color
- Abstract
Background: The aim of the study was not only to establish the applicability of color Doppler ultrasound of the neck vessels in patients with tumors of the oral cavity and the neck region but also to check whether the coexistence of sclerotic changes in the carotid arteries is essential in determination of the sequence of surgical procedure., Material/methods: Color Doppler ultrasound was performed on 110 patients, aged 15 -71 years with tumors of the oral cavity and the neck. The localization, size, echogenicity, as well as the tumor relationship to the surrounding structures and big vessels of the neck region was analyzed., Results: Compression of the veins was observed in 27 cases, and of the arteries only in 20 cases. Infiltration of the jugular vein was observed in 8 patients, whereas infiltration of the carotid artery were seen only in 6 patients. Severe internal carotid artery stenosis, due to arteriosclerosis, was observed in 10 patients. Three persons were suggested to be operated on, first due to carotid artery stenosis, later on, due to the oral cavity tumor., Conclusions: It was found that color Doppler ultrasound is useful in deciding upon the method of treatment, while the examination of the neck vessels is helpful in establishing the sequence of surgical procedures in patients with tumors and coexisting arteriosclerosis.
- Published
- 2004
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