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- PMID: 22729394
- UKPMCID: 22729394
- DOI: 10.1158/1055-9965.EPI-12-0229
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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; Paluch-Shimon, Shani-; Kaufman, Bella; ; Liljegren, Annelie; Lindblom, Annika; Olsson, HÃ¥kan; 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; Cajal, Teresa Ramóny; Stavropoulou, Alexandra V; BenÃtez, Javier; Hamann, Ute; ; Rookus, Matti; Aalfs, Cora M; de Lange, Judith L; Meijers-Heijboer, Hanne E J; Oosterwijk, Jan C; van Asperen, Christi J; Gómez GarcÃa, Encarna B; 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; Léoné, Mélanie; Gauthier-Villars, Marion; Caux-Moncoutier, Virginie; de Pauw, Antoine; Hardouin, Agnès; Berthet, Pascaline; Dreyfus, Hélène; Ferrer, Sandra Fert; Collonge-Rame, Marie-Agnès; 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; Aittomäki, 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;
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2012;21(8):1362-70.
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Full-text held externally
- PMID: 22729394
- UKPMCID: 22729394
- DOI: 10.1158/1055-9965.EPI-12-0229
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; P(difference), 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.
Bibliographic metadata
- Ding, Yuan C
- McGuffog, Lesley
- Healey, Sue
- Friedman, Eitan
- Laitman, Yael
- Paluch-Shimon, Shani-
- Kaufman, Bella
- Liljegren, Annelie
- Lindblom, Annika
- Olsson, HÃ¥kan
- 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
- Cajal, Teresa Ramóny
- Stavropoulou, Alexandra V
- BenÃtez, Javier
- Hamann, Ute
- Rookus, Matti
- Aalfs, Cora M
- de Lange, Judith L
- Meijers-Heijboer, Hanne E J
- Oosterwijk, Jan C
- van Asperen, Christi J
- Gómez GarcÃa, Encarna B
- 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
- Léoné, Mélanie
- Gauthier-Villars, Marion
- Caux-Moncoutier, Virginie
- de Pauw, Antoine
- Hardouin, Agnès
- Berthet, Pascaline
- Dreyfus, Hélène
- Ferrer, Sandra Fert
- Collonge-Rame, Marie-Agnès
- 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
- Aittomäki, 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
- 5U01CA113916, NCI NIH HHS, United States
- A11174, Cancer Research UK, United Kingdom
- A11668, Cancer Research UK, United Kingdom
- C1287/A10118, Cancer Research UK, United Kingdom
- C1287/A11990, Cancer Research UK, United Kingdom
- C5047/A8385, Cancer Research UK, United Kingdom
- CA-06-503, NCI NIH HHS, United States
- N02-CP-11019-50, NCI NIH HHS, United States
- N02-CP-65504, NCI NIH HHS, United States
- P01 CA16094, NCI NIH HHS, United States
- P30 CA033752, NCI NIH HHS, United States
- P30 CA042014, NCI NIH HHS, United States
- P30 CA13696, NCI NIH HHS, United States
- P30 ES009089, NIEHS NIH HHS, United States
- R01 CA074415, NCI NIH HHS, United States
- R01 CA140323, NCI NIH HHS, United States
- R01 CA22435, NCI NIH HHS, United States
- R01-CA083855, NCI NIH HHS, United States
- R01-CA102776, NCI NIH HHS, United States
- R01278978, PHS HHS, United States
- R01CA140323, NCI NIH HHS, United States
- R01CA74415, NCI NIH HHS, United States
- RC4 CA153828, NCI NIH HHS, United States
- RC4CA153828, NCI NIH HHS, United States
- U01 CA69398, NCI NIH HHS, United States
- U01 CA69417, NCI NIH HHS, United States
- U01 CA69446, NCI NIH HHS, United States
- U01 CA69467, NCI NIH HHS, United States
- U01 CA69631, NCI NIH HHS, United States
- U01 CA69638, NCI NIH HHS, United States
- U01CA69631, NCI NIH HHS, United States
- UL1 RR025764, NCRR NIH HHS, United States
- UL1 TR000124, NCATS NIH HHS, United States
- , Canadian Institutes of Health Research, Canada