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Genetic modifiers of CHEK2*1100delC-associated breast cancer risk.
Muranen, Taru A; Greco, Dario; Blomqvist, Carl; Aittomäki, Kristiina; Khan, Sofia; Hogervorst, Frans; Verhoef, Senno; Pharoah, Paul D P; Dunning, Alison M; Shah, Mitul; Luben, Robert; Bojesen, Stig E; Nordestgaard, Børge G; Schoemaker, Minouk; Swerdlow, Anthony; García-Closas, Montserrat; Figueroa, Jonine; Dörk, Thilo; Bogdanova, Natalia V; Hall, Per; Li, Jingmei; Khusnutdinova, Elza; Bermisheva, Marina; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Peto, Julian; Dos Santos Silva, Isabel; Couch, Fergus J; Olson, Janet E; Hillemans, Peter; Park-Simon, Tjoung-Won; Brauch, Hiltrud; Hamann, Ute; Burwinkel, Barbara; Marme, Frederik; Meindl, Alfons; Schmutzler, Rita K; Cox, Angela; Cross, Simon S; Sawyer, Elinor J; Tomlinson, Ian; Lambrechts, Diether; Moisse, Matthieu; Lindblom, Annika; Margolin, Sara; Hollestelle, Antoinette; Martens, John W M; Fasching, Peter A; Beckmann, Matthias W; Andrulis, Irene L.
Afiliação
  • Muranen TA; Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
  • Greco D; Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
  • Blomqvist C; Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
  • Aittomäki K; Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
  • Khan S; Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
  • Hogervorst F; Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands.
  • Verhoef S; Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands.
  • Pharoah PDP; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
  • Dunning AM; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Shah M; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
  • Luben R; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
  • Bojesen SE; Clinical Gerontology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Nordestgaard BG; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Schoemaker M; Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
  • Swerdlow A; Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
  • García-Closas M; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Figueroa J; Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
  • Dörk T; Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
  • Bogdanova NV; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
  • Hall P; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
  • Li J; Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.
  • Khusnutdinova E; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
  • Bermisheva M; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
  • Kristensen V; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
  • Borresen-Dale AL; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
  • Peto J; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Dos Santos Silva I; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Couch FJ; Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa, Russia.
  • Olson JE; Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa, Russia.
  • Hillemans P; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
  • Park-Simon TW; Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa, Russia.
  • Brauch H; Department of Genetics, Institute for Cancer Research, Radiumhospitalet, Oslo University Hospital, University of Oslo, Oslo, Norway.
  • Hamann U; Department of Clinical Molecular Biology, Oslo University Hospital, Oslo, Norway.
  • Burwinkel B; K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Marme F; Department of Genetics, Institute for Cancer Research, Radiumhospitalet, Oslo University Hospital, University of Oslo, Oslo, Norway.
  • Meindl A; K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Schmutzler RK; Department of Genetics, Institute for Cancer Research, Radiumhospitalet, Oslo University Hospital, University of Oslo, Oslo, Norway.
  • Cox A; Department of Clinical Molecular Biology, Oslo University Hospital, Oslo, Norway.
  • Cross SS; K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Sawyer EJ; Department of Oncology, Radiumhospitalet, Oslo University Hospital, University of Oslo, Oslo, Norway.
  • Tomlinson I; Department of Radiology, Radiumhospitalet, Oslo University Hospital, University of Oslo, Oslo, Norway.
  • Lambrechts D; National Resource Centre for Long-term Studies after Cancer, Cancer Clinic, Radiumhospitalet, Oslo University Hospital, University of Oslo, Oslo, Norway.
  • Moisse M; Department of Breast and Endocrine Surgery, Institute for Clinical Medicine, Ullevaal University Hospital, Oslo, Norway.
  • Lindblom A; Department of Clinical Molecular Biology, Institute of Clinical Medicine, Akershus University Hospital, Lørenskog, Norway.
  • Margolin S; Department of Oncology, Ullevaal University Hospital, University of Oslo, Oslo, Norway.
  • Hollestelle A; Department of Pathology, Akershus University Hospital, Lørenskog, Norway.
  • Martens JWM; Department of Surgery, Akershus University Hospital, Lørenskog, Norway.
  • Fasching PA; Department of Oncology, Haukeland University Hospital, Bergen, Norway.
  • Beckmann MW; Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway.
  • Andrulis IL; Norwegian Centre for Integrated Care and Telemedicine, University Hospital of North Norway, Tromsø, Norway.
Genet Med ; 19(5): 599-603, 2017 05.
Article em En | MEDLINE | ID: mdl-27711073
ABSTRACT

PURPOSE:

CHEK2*1100delC is a founder variant in European populations that confers a two- to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC).

METHODS:

Using genotype data from 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction.

RESULTS:

The PRS conferred odds ratios (OR) of 1.59 (95% CI 1.21-2.09) per standard deviation for BC for CHEK2*1100delC carriers and 1.58 (1.55-1.62) for noncarriers. No evidence of deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 (0.86-4.78) for CHEK2*1100delC carriers, placing them in the high risk category according to UK NICE guidelines. The OR for the lowest quintile was 0.52 (0.16-1.74), indicating a lifetime risk close to the population average.

CONCLUSION:

Our results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify carriers at a high lifetime risk for clinical actions.Genet Med advance online publication 06 October 2016.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Deleção de Sequência / Quinase do Ponto de Checagem 2 Tipo de estudo: Etiology_studies / Guideline / Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Deleção de Sequência / Quinase do Ponto de Checagem 2 Tipo de estudo: Etiology_studies / Guideline / Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article