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.
Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers / Susan J., Ramus; Antonis C., Antoniou; Karoline B., Kuchenbaecker; Penny, Soucy; Jonathan, Beesley; Xiaoqing, Chen; Lesley, Mcguffog; Olga M., Sinilnikova; Sue, Healey; Daniel, Barrowdale; Andrew, Lee; Mads, Thomassen; Anne Marie, Gerdes; Torben A., Kruse; Uffe Birk, Jensen; Anne Bine, Skytte; Maria A., Caligo; Annelie, Liljegren; Annika, Lindblom; Hakan, Olsson; Ulf, Kristoffersson; Marie Stenmark, Askmalm; B., Swe Brca Melin; Swe, Brca; Susan M., Domchek; Domchek, Sm; Katherine L., Nathanson; Timothy R., Rebbeck; 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; Flora E., Van Leeuwen; Cora M., Aalfs; Hanne E. J., Meijers Heijboer; Christi J., Van Asperen; K. E. P., Van Roozendaal; Nicoline, Hoogerbrugge; Margriet J., Collee; J., Margriet Collee; Mieke, Kriege; R. B., Hebon Van Der Luijt; Embrace, ; Embrace, Hebon; Susan, Peock; Debra, Frost; Steve D., Ellis; Radka, Platte; Elena, Fineberg; D., Gareth Evans; Fiona, Lalloo; Chris, Jacobs; Ros, Eeles; Julian, Adlard; Rosemarie, Davidson; Diana, Eccles; Trevor, Cole; Jackie, Cook; Joan, Paterson; Fiona, Douglas; Carole, Brewer; Shirley, Hodgson; Patrick J., Morrison; Lisa, Walker; Mary E., Porteous; M., John Kennedy; Harsh, Pathak; Andrew K., Godwin; Dominique Stoppa, Lyonnet; Virginie Caux, Moncoutier; D. E., Antoine Pauw; A., De Pauw; 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, ; S., Daly; Alex, Miron; Terry M., Beth; Mary Beth, Terry; M. B., Terry; Wendy K., Chung; John M., Esther; John, Em; Melissa, Southey; David, Goldgar; Christian F., Singer; Muy Kheng, Tea; Georg, Pfeiler; Anneliese Fink, Retter; Thomas V. O., Hansen; Tv, Hansen; Bent, Ejlertsen; Oskar Th, Johannsson; Kenneth, Offit; Tomas, Kirchhoff; Mia M., Gaudet; Joseph, Vijai; Mark, Robson; Marion, Piedmonte; Kelly Anne, Phillips; Linda Van, Le; James S., Hoffman; Amanda Ewart, Toland; A., Ewart Toland; Marco, Montagna; Silvia, Tognazzo; Evgeny, Imyanitov; Claudine, Isaacs; C., Issacs; Ramunas, Janavicius; Conxi, Lazaro; Ignacio, Blanco; Eva, Tornero; Matilde, Navarro; Kirsten B., Moysich; Beth Y., Karlan; Jenny, Gross; Edith, Olah; Tibor, Vaszko; Soo Hwang, Teo; Patricia A., Ganz; Mary S., Beattie; Cecelia M., Dorfling; Elizabeth J., Van Rensburg; Orland, Diez; Ava, Kwong; Rita K., Schmutzler; 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; A. B., Kconfab Spurdle; Kconfab, ; Susan L., Neuhausen; Neuhausen, Sl; Yuan Chun, Ding; Xianshu, Wang; Noralane, Lindor; Zachary, Fredericksen; V., Shane Pankratz; Paolo, Peterlongo; Siranoush, Manoukian; Bernard, Peissel; Daniela, Zaffaroni; Bernardo, Bonanni; Loris, Bernard; Riccardo, Dolcetti; Laura, Papi; Ottini, Laura; Paolo, Radice; Mark H., Greene; Phuong L., Mai; Irene L., Andrulis; Gord, Glendon; H., Ocgn Ozcelik; Ocgn, ; Paul D. P., Pharoah; Pharoah, Pd; Simon A., Gayther; Jacques, Simard; Douglas F., Easton; Fergus J., Couch; Georgia Chenevix, Trench; O. N., Behalf Of The Consortium Of Investigators Of Modifiers Of Brca1/2. - In: HUMAN MUTATION. - ISSN 1059-7794. - 33:4(2012), pp. 690-702. [10.1002/humu.22025]
Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers
OTTINI, LAURA;
2012
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.| File | Dimensione | Formato | |
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