%0 Journal Article %1 Antoniou.2008 %A Antoniou, Antonis C. %A Spurdle, Amanda B. %A Sinilnikova, Olga M. %A Healey, Sue %A Pooley, Karen A. %A Schmutzler, Rita K. %A Versmold, Beatrix %A Engel, Christoph %A Meindl, Alfons %A Arnold, Norbert %A Hofmann, Wera %A Sutter, Christian %A Niederacher, Dieter %A Deissler, Helmut %A Caldes, Trinidad %A Kämpjärvi, Kati %A Nevanlinna, Heli %A Simard, Jacques %A Beesley, Jonathan %A Chen, Xiaoqing %A Neuhausen, Susan L. %A Rebbeck, Timothy R. %A Wagner, Theresa %A Lynch, Henry T. %A Isaacs, Claudine %A Weitzel, Jeffrey %A Ganz, Patricia A. %A Daly, Mary B. %A Tomlinson, Gail %A Olopade, Olufunmilayo I. %A Blum, Joanne L. %A Couch, Fergus J. %A Peterlongo, Paolo %A Manoukian, Siranoush %A Barile, Monica %A Radice, Paolo %A Szabo, Csilla I. %A Pereira, Lutecia H Mateus, %A Greene, Mark H. %A Rennert, Gad %A Lejbkowicz, Flavio %A Barnett-Griness, Ofra %A Andrulis, Irene L. %A Ozcelik, Hilmi %A Gerdes, Anne-Marie %A Caligo, Maria A. %A Laitman, Yael %A Kaufman, Bella %A Milgrom, Roni %A Friedman, Eitan %A Domchek, Susan M. %A Nathanson, Katherine L. %A Osorio, Ana %A Llort, Gemma %A Milne, Roger L. %A Benítez, Javier %A Hamann, Ute %A Hogervorst, Frans B L, %A Manders, Peggy %A Ligtenberg, Marjolijn J L, %A van den Ouweland, Ans M W, %A Peock, Susan %A Cook, Margaret %A Platte, Radka %A Evans, D. Gareth %A Eeles, Rosalind %A Pichert, Gabriella %A Chu, Carol %A Eccles, Diana %A Davidson, Rosemarie %A Douglas, Fiona %A Godwin, Andrew K. %A Barjhoux, Laure %A Mazoyer, Sylvie %A Sobol, Hagay %A Bourdon, Violaine %A Eisinger, François %A Chompret, Agnès %A Capoulade, Corinne %A Bressac-de Paillerets, Brigitte %A Lenoir, Gilbert M. %A Gauthier-Villars, Marion %A Houdayer, Claude %A Stoppa-Lyonnet, Dominique %A Chenevix-Trench, Georgia %A Easton, Douglas F. %D 2008 %J American journal of human genetics %K Adult Aged Breast_Neoplasms/genetics Female Genes,_BRCA1 Genes,_BRCA2 Genetic_Predisposition_to_Disease/genetics Germ-Line_Mutation Humans MAP_Kinase_Kinase_Kinase_1/genetics Middle_Aged Polymorphism,_Single_Nucleotide Receptor,_Fibroblast_Growth_Factor,_Type_2/genetics Risk %N 4 %P 937–948 %T Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers %V 82 %X Germline mutations in BRCA1 and BRCA2 confer high risks of breast cancer. However, evidence suggests that these risks are modified by other genetic or environmental factors that cluster in families. A recent genome-wide association study has shown that common alleles at single nucleotide polymorphisms (SNPs) in FGFR2 (rs2981582), TNRC9 (rs3803662), and MAP3K1 (rs889312) are associated with increased breast cancer risks in the general population. To investigate whether these loci are also associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers, we genotyped these SNPs in a sample of 10,358 mutation carriers from 23 studies. The minor alleles of SNP rs2981582 and rs889312 were each associated with increased breast cancer risk in BRCA2 mutation carriers (per-allele hazard ratio HR = 1.32, 95\% CI: 1.20-1.45, p(trend) = 1.7 x 10(-8) and HR = 1.12, 95\% CI: 1.02-1.24, p(trend) = 0.02) but not in BRCA1 carriers. rs3803662 was associated with increased breast cancer risk in both BRCA1 and BRCA2 mutation carriers (per-allele HR = 1.13, 95\% CI: 1.06-1.20, p(trend) = 5 x 10(-5) in BRCA1 and BRCA2 combined). These loci appear to interact multiplicatively on breast cancer risk in BRCA2 mutation carriers. The differences in the effects of the FGFR2 and MAP3K1 SNPs between BRCA1 and BRCA2 carriers point to differences in the biology of BRCA1 and BRCA2 breast cancer tumors and confirm the distinct nature of breast cancer in BRCA1 mutation carriers.

@article{Antoniou.2008, abstract = {Germline mutations in BRCA1 and BRCA2 confer high risks of breast cancer. However, evidence suggests that these risks are modified by other genetic or environmental factors that cluster in families. A recent genome-wide association study has shown that common alleles at single nucleotide polymorphisms (SNPs) in FGFR2 (rs2981582), TNRC9 (rs3803662), and MAP3K1 (rs889312) are associated with increased breast cancer risks in the general population. To investigate whether these loci are also associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers, we genotyped these SNPs in a sample of 10,358 mutation carriers from 23 studies. The minor alleles of SNP rs2981582 and rs889312 were each associated with increased breast cancer risk in BRCA2 mutation carriers (per-allele hazard ratio [HR] = 1.32, 95\% CI: 1.20-1.45, p(trend) = 1.7 x 10(-8) and HR = 1.12, 95\% CI: 1.02-1.24, p(trend) = 0.02) but not in BRCA1 carriers. rs3803662 was associated with increased breast cancer risk in both BRCA1 and BRCA2 mutation carriers (per-allele HR = 1.13, 95\% CI: 1.06-1.20, p(trend) = 5 x 10(-5) in BRCA1 and BRCA2 combined). These loci appear to interact multiplicatively on breast cancer risk in BRCA2 mutation carriers. The differences in the effects of the FGFR2 and MAP3K1 SNPs between BRCA1 and BRCA2 carriers point to differences in the biology of BRCA1 and BRCA2 breast cancer tumors and confirm the distinct nature of breast cancer in BRCA1 mutation carriers.}, added-at = {2014-10-15T15:03:37.000+0200}, author = {Antoniou, Antonis C. and Spurdle, Amanda B. and Sinilnikova, Olga M. and Healey, Sue and Pooley, Karen A. and Schmutzler, Rita K. and Versmold, Beatrix and Engel, Christoph and Meindl, Alfons and Arnold, Norbert and Hofmann, Wera and Sutter, Christian and Niederacher, Dieter and Deissler, Helmut and Caldes, Trinidad and Kämpjärvi, Kati and Nevanlinna, Heli and Simard, Jacques and Beesley, Jonathan and Chen, Xiaoqing and Neuhausen, Susan L. and Rebbeck, Timothy R. and Wagner, Theresa and Lynch, Henry T. and Isaacs, Claudine and Weitzel, Jeffrey and Ganz, Patricia A. and Daly, Mary B. and Tomlinson, Gail and Olopade, Olufunmilayo I. and Blum, Joanne L. and Couch, Fergus J. and Peterlongo, Paolo and Manoukian, Siranoush and Barile, Monica and Radice, Paolo and Szabo, Csilla I. and {Pereira, Lutecia H Mateus} and Greene, Mark H. and Rennert, Gad and Lejbkowicz, Flavio and Barnett-Griness, Ofra and Andrulis, Irene L. and Ozcelik, Hilmi and Gerdes, Anne-Marie and Caligo, Maria A. and Laitman, Yael and Kaufman, Bella and Milgrom, Roni and Friedman, Eitan and Domchek, Susan M. and Nathanson, Katherine L. and Osorio, Ana and Llort, Gemma and Milne, Roger L. and Benítez, Javier and Hamann, Ute and {Hogervorst, Frans B L} and Manders, Peggy and {Ligtenberg, Marjolijn J L} and {van den Ouweland, Ans M W} and Peock, Susan and Cook, Margaret and Platte, Radka and Evans, D. Gareth and Eeles, Rosalind and Pichert, Gabriella and Chu, Carol and Eccles, Diana and Davidson, Rosemarie and Douglas, Fiona and Godwin, Andrew K. and Barjhoux, Laure and Mazoyer, Sylvie and Sobol, Hagay and Bourdon, Violaine and Eisinger, François and Chompret, Agnès and Capoulade, Corinne and {Bressac-de Paillerets}, Brigitte and Lenoir, Gilbert M. and Gauthier-Villars, Marion and Houdayer, Claude and Stoppa-Lyonnet, Dominique and Chenevix-Trench, Georgia and Easton, Douglas F.}, biburl = {https://www.bibsonomy.org/bibtex/28eca151f10b704536a735bd61a471b22/drtester}, interhash = {cdfed1c0a83ac40efdd7c33c4250f91d}, intrahash = {8eca151f10b704536a735bd61a471b22}, journal = {American journal of human genetics}, keywords = {Adult Aged Breast_Neoplasms/genetics Female Genes,_BRCA1 Genes,_BRCA2 Genetic_Predisposition_to_Disease/genetics Germ-Line_Mutation Humans MAP_Kinase_Kinase_Kinase_1/genetics Middle_Aged Polymorphism,_Single_Nucleotide Receptor,_Fibroblast_Growth_Factor,_Type_2/genetics Risk}, number = 4, pages = {937–948}, timestamp = {2014-10-15T15:03:37.000+0200}, title = {Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers}, volume = 82, year = 2008 }