A Nonsynonymous Polymorphism in IRS1 Modifies Risk of Developing Breast and Ovarian Cancers in BRCA1 and Ovarian Cancer in BRCA2 Mutation Carriers

Ding, Yuan C., McGuffog, Lesley, Healey, Sue, Friedman, Eitan, Laitman, Yael, Shani-Paluch-Shimon, Kaufman, Bella, Liljegren, Annelie, Lindblom, Annika, Olsson, Hakan, Kristoffersson, Ulf, Stenmark-Askmalm, Marie, Melin, Beatrice, Domchek, Susan M., Nathanson, Katherine L., Rebbeck, Timothy R., Jakubowska, Anna, Lubinski, Jan, Jaworska, Katarzyna, Durda, Katarzyna, Gronwald, Jacek, Huzarski, Tomasz, Cybulski, Cezary, Byrski, Tomasz, Osorio, Ana, Ramony Cajal, Teresa, Stavropoulou, Alexandra V., Benitez, Javier, Hamann, Ute, Rookus, Matti, Aalfs, Cora M., de Lange, Judith L., Meijers-Heijboer, Hanne E. J., Oosterwijk, Jan C., van Asperen, Christi J., Garcia, Encarna B. Gomez, Hoogerbrugge, Nicoline, Jager, Agnes, van der Luijt, Rob B., Easton, Douglas F., Peock, Susan, Frost, Debra, Ellis, Steve D., Platte, Radka, Fineberg, Elena, Evans, D. Gareth, Lalloo, Fiona, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Eccles, Diana, Cole, Trevor, Cook, Jackie, Brewer, Carole, Tischkowitz, Marc, Godwin, Andrew K., Pathak, Harsh, Stoppa-Lyonnet, Dominique, Sinilnikova, Olga M., Mazoyer, Sylvie, Barjhoux, Laure, Leone, Melanie, Gauthier-Villars, Marion, Caux-Moncoutier, Virginie, de Pauw, Antoine, Hardouin, Agnes, Berthet, Pascaline, Dreyfus, Helene, Ferrer, Sandra Fert, Collonge-Rame, Marie-Agnes, Sokolowska, Johanna, Buys, Saundra, Daly, Mary, Miron, Alex, Terry, Mary Beth, Chung, Wendy, John, Esther M., Southey, Melissa, Goldgar, David, Singer, Christian F., Tea, Muy-Kheng Maria, Gschwantler-Kaulich, Daphne, Fink-Retter, Anneliese, Hansen, Thomas V. O., Ejlertsen, Bent, Johannsson, Oskar T., Offit, Kenneth, Sarrel, Kara, Gaudet, Mia M., Vijai, Joseph, Robson, Mark, Piedmonte, Marion R., Andrews, Lesley, Cohn, David, DeMars, Leslie R., DiSilvestro, Paul, Rodriguez, Gustavo, Toland, Amanda Ewart, Montagna, Marco, Agata, Simona, Imyanitov, Evgeny, Isaacs, Claudine, Janavicius, Ramunas, Lazaro, Conxi, Blanco, Ignacio, Ramus, Susan J., Sucheston, Lara, Karlan, Beth Y., Gross, Jenny, Ganz, Patricia A., Beattie, Mary S., Schmutzler, Rita K., Wappenschmidt, Barbara, Meindl, Alfons, Arnold, Norbert, Niederacher, Dieter, Preisler-Adams, Sabine, Gadzicki, Dorotehea, Varon-Mateeva, Raymonda, Deissler, Helmut, Gehrig, Andrea, Sutter, Christian, Kast, Karin, Nevanlinna, Heli, Aittomaki, Kristiina, Simard, Jacques, Spurdle, Amanda B., Beesley, Jonathan, Chen, Xiaoqing, Tomlinson, Gail E., Weitzel, Jeffrey, Garber, Judy E., Olopade, Olufunmilayo I., Rubinstein, Wendy S., Tung, Nadine, Blum, Joanne L., Narod, Steven A., Brummel, Sean, Gillen, Daniel L., Lindor, Noralane, Fredericksen, Zachary, Pankratz, Vernon S., Couch, Fergus J., Radice, Paolo, Peterlongo, Paolo, Greene, Mark H., Loud, Jennifer T., Mai, Phuong L., Andrulis, Irene L., Glendon, Gord, Ozcelik, Hilmi, Gerdes, Anne-Marie, Thomassen, Mads, Jensen, Uffe Birk, Skytte, Anne-Bine, Caligo, Maria A., Lee, Andrew, Chenevix-Trench, Georgia, Antoniou, Antonis C. and Neuhausen, Susan L. (2012) A Nonsynonymous Polymorphism in IRS1 Modifies Risk of Developing Breast and Ovarian Cancers in BRCA1 and Ovarian Cancer in BRCA2 Mutation Carriers. Cancer Epidemiology Biomarkers & Prevention, 21 8: 1362-1370.

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Author Ding, Yuan C.
McGuffog, Lesley
Healey, Sue
Friedman, Eitan
Laitman, Yael
Shani-Paluch-Shimon
Kaufman, Bella
Liljegren, Annelie
Lindblom, Annika
Olsson, Hakan
Kristoffersson, Ulf
Stenmark-Askmalm, Marie
Melin, Beatrice
Domchek, Susan M.
Nathanson, Katherine L.
Rebbeck, Timothy R.
Jakubowska, Anna
Lubinski, Jan
Jaworska, Katarzyna
Durda, Katarzyna
Gronwald, Jacek
Huzarski, Tomasz
Cybulski, Cezary
Byrski, Tomasz
Osorio, Ana
Ramony Cajal, Teresa
Stavropoulou, Alexandra V.
Benitez, Javier
Hamann, Ute
Rookus, Matti
Aalfs, Cora M.
de Lange, Judith L.
Meijers-Heijboer, Hanne E. J.
Oosterwijk, Jan C.
van Asperen, Christi J.
Garcia, Encarna B. Gomez
Hoogerbrugge, Nicoline
Jager, Agnes
van der Luijt, Rob B.
Easton, Douglas F.
Peock, Susan
Frost, Debra
Ellis, Steve D.
Platte, Radka
Fineberg, Elena
Evans, D. Gareth
Lalloo, Fiona
Izatt, Louise
Eeles, Ros
Adlard, Julian
Davidson, Rosemarie
Eccles, Diana
Cole, Trevor
Cook, Jackie
Brewer, Carole
Tischkowitz, Marc
Godwin, Andrew K.
Pathak, Harsh
Stoppa-Lyonnet, Dominique
Sinilnikova, Olga M.
Mazoyer, Sylvie
Barjhoux, Laure
Leone, Melanie
Gauthier-Villars, Marion
Caux-Moncoutier, Virginie
de Pauw, Antoine
Hardouin, Agnes
Berthet, Pascaline
Dreyfus, Helene
Ferrer, Sandra Fert
Collonge-Rame, Marie-Agnes
Sokolowska, Johanna
Buys, Saundra
Daly, Mary
Miron, Alex
Terry, Mary Beth
Chung, Wendy
John, Esther M.
Southey, Melissa
Goldgar, David
Singer, Christian F.
Tea, Muy-Kheng Maria
Gschwantler-Kaulich, Daphne
Fink-Retter, Anneliese
Hansen, Thomas V. O.
Ejlertsen, Bent
Johannsson, Oskar T.
Offit, Kenneth
Sarrel, Kara
Gaudet, Mia M.
Vijai, Joseph
Robson, Mark
Piedmonte, Marion R.
Andrews, Lesley
Cohn, David
DeMars, Leslie R.
DiSilvestro, Paul
Rodriguez, Gustavo
Toland, Amanda Ewart
Montagna, Marco
Agata, Simona
Imyanitov, Evgeny
Isaacs, Claudine
Janavicius, Ramunas
Lazaro, Conxi
Blanco, Ignacio
Ramus, Susan J.
Sucheston, Lara
Karlan, Beth Y.
Gross, Jenny
Ganz, Patricia A.
Beattie, Mary S.
Schmutzler, Rita K.
Wappenschmidt, Barbara
Meindl, Alfons
Arnold, Norbert
Niederacher, Dieter
Preisler-Adams, Sabine
Gadzicki, Dorotehea
Varon-Mateeva, Raymonda
Deissler, Helmut
Gehrig, Andrea
Sutter, Christian
Kast, Karin
Nevanlinna, Heli
Aittomaki, Kristiina
Simard, Jacques
Spurdle, Amanda B.
Beesley, Jonathan
Chen, Xiaoqing
Tomlinson, Gail E.
Weitzel, Jeffrey
Garber, Judy E.
Olopade, Olufunmilayo I.
Rubinstein, Wendy S.
Tung, Nadine
Blum, Joanne L.
Narod, Steven A.
Brummel, Sean
Gillen, Daniel L.
Lindor, Noralane
Fredericksen, Zachary
Pankratz, Vernon S.
Couch, Fergus J.
Radice, Paolo
Peterlongo, Paolo
Greene, Mark H.
Loud, Jennifer T.
Mai, Phuong L.
Andrulis, Irene L.
Glendon, Gord
Ozcelik, Hilmi
Gerdes, Anne-Marie
Thomassen, Mads
Jensen, Uffe Birk
Skytte, Anne-Bine
Caligo, Maria A.
Lee, Andrew
Chenevix-Trench, Georgia
Antoniou, Antonis C.
Neuhausen, Susan L.
Title A Nonsynonymous Polymorphism in IRS1 Modifies Risk of Developing Breast and Ovarian Cancers in BRCA1 and Ovarian Cancer in BRCA2 Mutation Carriers
Journal name Cancer Epidemiology Biomarkers & Prevention   Check publisher's open access policy
ISSN 1055-9965
Publication date 2012-08
Sub-type Article (original research)
DOI 10.1158/1055-9965.EPI-12-0229
Volume 21
Issue 8
Start page 1362
End page 1370
Total pages 9
Place of publication Philadelphia, PA, U.S.A.
Publisher American Association for Cancer Research
Collection year 2013
Language eng
Abstract Background: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers. Methods: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers. Results: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06–1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39–3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28–2.70; class I HR, 0.86; 95%CI, 0.69–1.09; Pdifference, 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03). Conclusion: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers. Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(8); 1362–70. ©2012 AACR.
Keyword Amino-Acid Polymorphism
Growth-Factor-I
Genetic-Variation
Insulin
Receptor
Expression
Igf
Neoplasia
Proteins
Family
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
 
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Created: Tue, 25 Sep 2012, 15:18:42 EST by Matthew Lamb on behalf of School of Medicine