Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
Zeng, Chenjie (författare)
Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, 2525 West End Ave,8th Floor, Nashville, TN 37203 USA.
Guo, Xingyi (författare)
Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, 2525 West End Ave,8th Floor, Nashville, TN 37203 USA.
Long, Jirong (författare)
Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, 2525 West End Ave,8th Floor, Nashville, TN 37203 USA.
Univ Helsinki, Helsinki Univ Hosp, Dept Oncol, Helsinki, Finland.
Blot, William J. (författare)
Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, 2525 West End Ave,8th Floor, Nashville, TN 37203 USA.;Int Epidemiol Inst, Rockville, MD USA.
Bogdanova, Natalia V. (författare)
Hannover Med Sch, Dept Radiat Oncol, Hannover, Germany.
Bojesen, Stig E. (författare)
Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Herlev, Denmark.;Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
Bonanni, Bernardo (författare)
Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy.
Borresen-Dale, Anne-Lise (författare)
Radiumhosp, Oslo Univ Hosp, Inst Canc Res, Dept Genet, Oslo, Norway.;Univ Oslo, Fac Med, Inst Clin Med, KG Jebsen Ctr Breast Canc Res, Oslo, Norway.
Brand, Judith S. (författare)
Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
Brauch, Hiltrud (författare)
Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany.;Univ Tubingen, Tubingen, Germany.;German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany.
Brennan, Paul (författare)
Int Agcy Res Canc, Lyon, France.
Brenner, Hermann (författare)
German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.;German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany.;German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
Broeks, Annegien (författare)
Radiumhosp, Oslo Univ Hosp, Inst Canc Res, Dept Genet, Oslo, Norway.;Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands.
Bruening, Thomas (författare)
Inst Ruhr Univ Bochum, Inst Prevent & Occupat Med German Social Accident, Bochum, Germany.
Univ Utah, Sch Med, Dept Med, Huntsman Canc Inst, Salt Lake City, UT USA.
Cai, Qiuyin (författare)
Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, 2525 West End Ave,8th Floor, Nashville, TN 37203 USA.
Caldes, Trinidad (författare)
Hosp Clin San Carlos, IdISSC Inst Invest Sanitaria Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain.
Campbell, Ian (författare)
Peter MacCallum Canc Ctr, Canc Gene Lab, Melbourne, Vic, Australia.
Carpenter, Jane (författare)
Univ Sydney, Westmead Millennium Inst, Australian Breast Canc Tissue Bank, Sydney, NSW, Australia.
Chang-Claude, Jenny (författare)
German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.;Univ Med Ctr Hamburg Eppendorf, UCCH, Hamburg, Germany.
Choi, Ji-Yeob (författare)
Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.;Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea.;Seoul Natl Univ, Canc Res Inst, Seoul, South Korea.
Claes, Kathleen B. M. (författare)
Univ Ghent, Ctr Med Genet, Ghent, Belgium.
Clarke, Christine (författare)
Univ Sydney, Westmead Millenium Inst Med Res, Sydney, NSW, Australia.
Canc Res Initiat Fdn, Subang Jaya, Selangor, Malaysia.;Univ Malaya, Med Ctr, Canc Res Inst, Breast Canc Res Unit, Kuala Lumpur, Malaysia.
Healey, Sue (författare)
QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld, Australia.
Hogervorst, Frans B. L. (författare)
Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands.
Verhoef, Senno (författare)
Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands.
Hendricks, Carolyn B. (författare)
Suburban Hosp, Bethesda, MD USA.;City Hope Natl Med Ctr, Clin Canc Genet Community Res Network, Duarte, CA USA.
Hillemanns, Peter (författare)
Hannover Med Sch, Clin Obstet & Gynaecol, Hannover, Germany.
Hollestelle, Antoinette (författare)
Erasmus MC Canc Inst, Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands.
Hulick, Peter J. (författare)
NorthShore Univ HealthSyst, Ctr Med Genet, Evanston, IL USA.
Hunter, David J. (författare)
Harvard Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
Imyanitov, Evgeny N. (författare)
NN Petrov Inst Oncol, St Petersburg, Russia.
Isaacs, Claudine (författare)
Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
Ito, Hidemi (författare)
Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi, Japan.
Jakubowska, Anna (författare)
Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
Janavicius, Ramunas (författare)
State Res Inst, Ctr Innovat Med, Vilnius, Lithuania.
Jaworska-Bieniek, Katarzyna (författare)
Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
Jensen, Uffe Birk (författare)
Aarhus Univ Hosp, Dept Clin Genet, Aarhus N, Denmark.
John, Esther M. (författare)
Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA USA.;Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA.;Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA.
Beauparlant, Charles Joly (författare)
Ctr Hosp Univ Quebec Res Ctr, Genom Ctr, Quebec City, PQ, Canada.;Univ Laval, Quebec City, PQ, Canada.
Jones, Michael (författare)
Inst Canc Res, Div Genet & Epidemiol, London, England.
Kabisch, Maria (författare)
German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany.
Kang, Daehee (författare)
Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.;Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea.;Seoul Natl Univ, Canc Res Inst, Seoul, South Korea.
Karlan, Beth Y. (författare)
Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA.
Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON, Canada.;Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada.
Harvard Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
Kwong, Ava (författare)
Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China.;Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China.
Laitman, Yael (författare)
Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, Tel Hashomer, Israel.
Univ Calif San Francisco, Dept Med Genet, San Francisco, CA 94143 USA.
Offit, Kenneth (författare)
Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, Clin Genet Res Lab, 1275 York Ave, New York, NY 10021 USA.;Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, 1275 York Ave, New York, NY 10021 USA.
Olah, Edith (författare)
Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary.
Olopade, Olufunmilayo I. (författare)
Univ Chicago, Med Ctr, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA.
Olswold, Curtis (författare)
Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
Osorio, Ana (författare)
Spanish Natl Canc Ctr CNIO, Human Canc Genet Program, Human Genet Grp, Madrid, Spain.;Biomed Network Rare Dis CIBERER, Madrid, Spain.
Papi, Laura (författare)
Univ Florence, Dept Biomed Expt & Clin Sci, Unit Med Genet, Florence, Italy.
Park-Simon, Tjoung-Won (författare)
Hannover Med Sch, Clin Obstet & Gynaecol, Hannover, Germany.
Paulsson-Karlsson, Ylva (författare)
Uppsala universitet,Institutionen för immunologi, genetik och patologi
Peeters, Stephanie (författare)
Univ Hosp Gasthuisberg, Leuven, Belgium.
Peissel, Bernard (författare)
INT, Fdn IRCCS Ist Ricovero Cura Carattere Sci, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy.
Peterlongo, Paolo (författare)
Fdn Ist FIRC Italian Fdn Canc Res Oncol Mol, IFOM, Milan, Italy.
Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH USA.
Tung, Nadine (författare)
Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA.
Turnbull, Clare (författare)
Inst Canc Res, Sect Canc Genet, London, England.
van den Ouweland, Ans M. W. (författare)
Erasmus Univ, Med Ctr, Dept Clin Genet, Rotterdam, Netherlands.
van Rensburg, Elizabeth J. (författare)
Univ Pretoria, Dept Genet, Pretoria, South Africa.
ven den Berg, David (författare)
Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
Vijai, Joseph (författare)
Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, Clin Genet Res Lab, 1275 York Ave, New York, NY 10021 USA.;Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, 1275 York Ave, New York, NY 10021 USA.
Wang-Gohrke, Shan (författare)
Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany.
Weitzel, Jeffrey N. (författare)
City Hope Natl Med Ctr, Clin Canc Genet Community Res Network, Clin Canc Genet, Duarte, CA USA.
Whittemore, Alice S. (författare)
Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA.;Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA.
Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
Ämnesord
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)