Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers

Antonis C Antoniou; Olga M Sinilnikova; Lesley McGuffog; Sue Healey; Heli Nevanlinna; Tuomas Heikkinen; Jacques Simard; Amanda B Spurdle; Jonathan Beesley; Xiaoqing Chen; Susan L Neuhausen; Yuan C Ding; Fergus J Couch; Xianshu Wang; Zachary Fredericksen; Paolo Peterlongo; Bernard Peissel; Bernardo Bonanni; Alessandra Viel; Loris Bernard; Paolo Radice; Csilla I Szabo; Lenka Foretova; Michal Zikan; Kathleen Claes; Mark H Greene; Phuong L Mai; Gad Rennert; Flavio Lejbkowicz; Irene L Andrulis; Hilmi Ozcelik; Gord Glendon; Anne-Marie Gerdes; Mads Thomassen; Lone Sunde; Maria A Caligo; Yael Laitman; Tair Kontorovich; Shimrit Cohen; Bella Kaufman; Efrat Dagan; Ruth Gershoni Baruch; Eitan Friedman; Katja Harbst; Gisela Barbany-Bustinza; Johanna Rantala; Hans Ehrencrona; Per Karlsson; Susan M Domchek; Katherine L Nathanson; Ana Osorio; Ignacio Blanco; Adriana Lasa; Javier Benítez; Ute Hamann; Frans B L Hogervorst; Matti A Rookus; J Margriet Collee; Peter Devilee; Marjolijn J Ligtenberg; Rob B van der Luijt; Cora M Aalfs; Quinten Waisfisz; Juul Wijnen; Cornelis E P van Roozendaal; Susan Peock; Margaret Cook; Debra Frost; Clare Oliver; Radka Platte; D Gareth Evans; Fiona Lalloo; Rosalind Eeles; Louise Izatt; Rosemarie Davidson; Carol Chu; Diana Eccles; Trevor Cole; Shirley Hodgson; Andrew K Godwin; Dominique Stoppa-Lyonnet; Bruno Buecher; Mélanie Léoné; Brigitte Bressac-de Paillerets; Audrey Remenieras; Olivier Caron; Gilbert M Lenoir; Nicolas Sevenet; Michel Longy; Sandra Fert Ferrer; Fabienne Prieur; David Goldgar; Alexander Miron; Esther M John; Saundra S Buys; Mary B Daly; John L Hopper; Mary Beth Terry; Yosuf Yassin; Christian Singer; Daphne Gschwantler-Kaulich; Christine Staudigl; Thomas v O Hansen; Rosa Bjork Barkardottir; Tomas Kirchhoff; Prodipto Pal; Kristi Kosarin; Kenneth Offit; Marion Piedmonte; Gustavo C Rodriguez; Katie Wakeley; John F Boggess; Jack Basil; Peter E Schwartz; Stephanie V Blank; Amanda E Toland; Marco Montagna; Cinzia Casella; Evgeny N Imyanitov; Anna Allavena; Rita K Schmutzler; Beatrix Versmold; Christoph Engel; Alfons Meindl; Nina Ditsch; Norbert Arnold; Dieter Niederacher; Helmut Deissler; Britta Fiebig; Christian Suttner; Ines Schönbuchner; Dorothea Gadzicki; Trinidad Caldes; Miguel de la Hoya; Karen A Pooley; Douglas F Easton; Georgia Chenevix-Trench

doi:10.1093/hmg/ddp372

Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers

Antonis C Antoniou, Olga M Sinilnikova, Lesley McGuffog, Sue Healey, Heli Nevanlinna, Tuomas Heikkinen, Jacques Simard, Amanda B Spurdle, Jonathan Beesley, Xiaoqing Chen, Susan L Neuhausen, Yuan C Ding, Fergus J Couch, Xianshu Wang, Zachary Fredericksen, Paolo Peterlongo, Bernard Peissel, Bernardo Bonanni, Alessandra Viel, Loris BernardPaolo Radice, Csilla I Szabo, Lenka Foretova, Michal Zikan, Kathleen Claes, Mark H Greene, Phuong L Mai, Gad Rennert, Flavio Lejbkowicz, Irene L Andrulis, Hilmi Ozcelik, Gord Glendon, Anne-Marie Gerdes, Mads Thomassen, Lone Sunde, Maria A Caligo, Yael Laitman, Tair Kontorovich, Shimrit Cohen, Bella Kaufman, Efrat Dagan, Ruth Gershoni Baruch, Eitan Friedman, Katja Harbst, Gisela Barbany-Bustinza, Johanna Rantala, Hans Ehrencrona, Per Karlsson, Susan M Domchek, Katherine L Nathanson, Ana Osorio, Ignacio Blanco, Adriana Lasa, Javier Benítez, Ute Hamann, Frans B L Hogervorst, Matti A Rookus, J Margriet Collee, Peter Devilee, Marjolijn J Ligtenberg, Rob B van der Luijt, Cora M Aalfs, Quinten Waisfisz, Juul Wijnen, Cornelis E P van Roozendaal, Susan Peock, Margaret Cook, Debra Frost, Clare Oliver, Radka Platte, D Gareth Evans, Fiona Lalloo, Rosalind Eeles, Louise Izatt, Rosemarie Davidson, Carol Chu, Diana Eccles, Trevor Cole, Shirley Hodgson, Andrew K Godwin, Dominique Stoppa-Lyonnet, Bruno Buecher, Mélanie Léoné, Brigitte Bressac-de Paillerets, Audrey Remenieras, Olivier Caron, Gilbert M Lenoir, Nicolas Sevenet, Michel Longy, Sandra Fert Ferrer, Fabienne Prieur, David Goldgar, Alexander Miron, Esther M John, Saundra S Buys, Mary B Daly, John L Hopper, Mary Beth Terry, Yosuf Yassin, Christian Singer, Daphne Gschwantler-Kaulich, Christine Staudigl, Thomas v O Hansen, Rosa Bjork Barkardottir, Tomas Kirchhoff, Prodipto Pal, Kristi Kosarin, Kenneth Offit, Marion Piedmonte, Gustavo C Rodriguez, Katie Wakeley, John F Boggess, Jack Basil, Peter E Schwartz, Stephanie V Blank, Amanda E Toland, Marco Montagna, Cinzia Casella, Evgeny N Imyanitov, Anna Allavena, Rita K Schmutzler, Beatrix Versmold, Christoph Engel, Alfons Meindl, Nina Ditsch, Norbert Arnold, Dieter Niederacher, Helmut Deissler, Britta Fiebig, Christian Suttner, Ines Schönbuchner, Dorothea Gadzicki, Trinidad Caldes, Miguel de la Hoya, Karen A Pooley, Douglas F Easton, Georgia Chenevix-Trench

Landspitali - The National University Hospital of Iceland

Research output: Contribution to journal › Article › peer-review

Abstract

Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 x 10(-4)]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not.

Original language	English
Journal	Human Molecular Genetics
DOIs	https://doi.org/10.1093/hmg/ddp372
Publication status	Published - 15 Nov 2009

Other keywords

Adult
Aged
Aged, 80 and over
BRCA1 Protein
BRCA2 Protein
Breast Neoplasms
Chromosomes, Human, Pair 2
Chromosomes, Human, Pair 8
Female
Follow-Up Studies
Genetic Predisposition to Disease
Genetic Variation
Genetics, Population
Genome-Wide Association Study
Heterozygote
Humans
Microfilament Proteins
Middle Aged
Mutation
Polymorphism, Single Nucleotide
Young Adult

Access to Document

10.1093/hmg/ddp372

http://dx.doi.org/10.1093/hmg/ddp372

Cite this

Antoniou, A. C., Sinilnikova, O. M., McGuffog, L., Healey, S., Nevanlinna, H., Heikkinen, T., Simard, J., Spurdle, A. B., Beesley, J., Chen, X., Neuhausen, S. L., Ding, Y. C., Couch, F. J., Wang, X., Fredericksen, Z., Peterlongo, P., Peissel, B., Bonanni, B., Viel, A., ... Chenevix-Trench, G. (2009). Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers. Human Molecular Genetics. https://doi.org/10.1093/hmg/ddp372

@article{4044a4e3f95f407493fee9bfa4118677,

title = "Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers",

abstract = "Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 x 10(-4)]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not.",

keywords = "Adult, Aged, Aged, 80 and over, BRCA1 Protein, BRCA2 Protein, Breast Neoplasms, Chromosomes, Human, Pair 2, Chromosomes, Human, Pair 8, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genetic Variation, Genetics, Population, Genome-Wide Association Study, Heterozygote, Humans, Microfilament Proteins, Middle Aged, Mutation, Polymorphism, Single Nucleotide, Young Adult, Adult, Aged, Aged, 80 and over, BRCA1 Protein, BRCA2 Protein, Breast Neoplasms, Chromosomes, Human, Pair 2, Chromosomes, Human, Pair 8, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genetic Variation, Genetics, Population, Genome-Wide Association Study, Heterozygote, Humans, Microfilament Proteins, Middle Aged, Mutation, Polymorphism, Single Nucleotide, Young Adult",

author = "Antoniou, {Antonis C} and Sinilnikova, {Olga M} and Lesley McGuffog and Sue Healey and Heli Nevanlinna and Tuomas Heikkinen and Jacques Simard and Spurdle, {Amanda B} and Jonathan Beesley and Xiaoqing Chen and Neuhausen, {Susan L} and Ding, {Yuan C} and Couch, {Fergus J} and Xianshu Wang and Zachary Fredericksen and Paolo Peterlongo and Bernard Peissel and Bernardo Bonanni and Alessandra Viel and Loris Bernard and Paolo Radice and Szabo, {Csilla I} and Lenka Foretova and Michal Zikan and Kathleen Claes and Greene, {Mark H} and Mai, {Phuong L} and Gad Rennert and Flavio Lejbkowicz and Andrulis, {Irene L} and Hilmi Ozcelik and Gord Glendon and Anne-Marie Gerdes and Mads Thomassen and Lone Sunde and Caligo, {Maria A} and Yael Laitman and Tair Kontorovich and Shimrit Cohen and Bella Kaufman and Efrat Dagan and Baruch, {Ruth Gershoni} and Eitan Friedman and Katja Harbst and Gisela Barbany-Bustinza and Johanna Rantala and Hans Ehrencrona and Per Karlsson and Domchek, {Susan M} and Nathanson, {Katherine L} and Ana Osorio and Ignacio Blanco and Adriana Lasa and Javier Ben{\'i}tez and Ute Hamann and Hogervorst, {Frans B L} and Rookus, {Matti A} and Collee, {J Margriet} and Peter Devilee and Ligtenberg, {Marjolijn J} and {van der Luijt}, {Rob B} and Aalfs, {Cora M} and Quinten Waisfisz and Juul Wijnen and {van Roozendaal}, {Cornelis E P} and Susan Peock and Margaret Cook and Debra Frost and Clare Oliver and Radka Platte and Evans, {D Gareth} and Fiona Lalloo and Rosalind Eeles and Louise Izatt and Rosemarie Davidson and Carol Chu and Diana Eccles and Trevor Cole and Shirley Hodgson and Godwin, {Andrew K} and Dominique Stoppa-Lyonnet and Bruno Buecher and M{\'e}lanie L{\'e}on{\'e} and {Bressac-de Paillerets}, Brigitte and Audrey Remenieras and Olivier Caron and Lenoir, {Gilbert M} and Nicolas Sevenet and Michel Longy and Ferrer, {Sandra Fert} and Fabienne Prieur and David Goldgar and Alexander Miron and John, {Esther M} and Buys, {Saundra S} and Daly, {Mary B} and Hopper, {John L} and Terry, {Mary Beth} and Yosuf Yassin and Christian Singer and Daphne Gschwantler-Kaulich and Christine Staudigl and Hansen, {Thomas v O} and Barkardottir, {Rosa Bjork} and Tomas Kirchhoff and Prodipto Pal and Kristi Kosarin and Kenneth Offit and Marion Piedmonte and Rodriguez, {Gustavo C} and Katie Wakeley and Boggess, {John F} and Jack Basil and Schwartz, {Peter E} and Blank, {Stephanie V} and Toland, {Amanda E} and Marco Montagna and Cinzia Casella and Imyanitov, {Evgeny N} and Anna Allavena and Schmutzler, {Rita K} and Beatrix Versmold and Christoph Engel and Alfons Meindl and Nina Ditsch and Norbert Arnold and Dieter Niederacher and Helmut Deissler and Britta Fiebig and Christian Suttner and Ines Sch{\"o}nbuchner and Dorothea Gadzicki and Trinidad Caldes and {de la Hoya}, Miguel and Pooley, {Karen A} and Easton, {Douglas F} and Georgia Chenevix-Trench",

year = "2009",

month = nov,

day = "15",

doi = "10.1093/hmg/ddp372",

language = "English",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

}

Antoniou, AC, Sinilnikova, OM, McGuffog, L, Healey, S, Nevanlinna, H, Heikkinen, T, Simard, J, Spurdle, AB, Beesley, J, Chen, X, Neuhausen, SL, Ding, YC, Couch, FJ, Wang, X, Fredericksen, Z, Peterlongo, P, Peissel, B, Bonanni, B, Viel, A, Bernard, L, Radice, P, Szabo, CI, Foretova, L, Zikan, M, Claes, K, Greene, MH, Mai, PL, Rennert, G, Lejbkowicz, F, Andrulis, IL, Ozcelik, H, Glendon, G, Gerdes, A-M, Thomassen, M, Sunde, L, Caligo, MA, Laitman, Y, Kontorovich, T, Cohen, S, Kaufman, B, Dagan, E, Baruch, RG, Friedman, E, Harbst, K, Barbany-Bustinza, G, Rantala, J, Ehrencrona, H, Karlsson, P, Domchek, SM, Nathanson, KL, Osorio, A, Blanco, I, Lasa, A, Benítez, J, Hamann, U, Hogervorst, FBL, Rookus, MA, Collee, JM, Devilee, P, Ligtenberg, MJ, van der Luijt, RB, Aalfs, CM, Waisfisz, Q, Wijnen, J, van Roozendaal, CEP, Peock, S, Cook, M, Frost, D, Oliver, C, Platte, R, Evans, DG, Lalloo, F, Eeles, R, Izatt, L, Davidson, R, Chu, C, Eccles, D, Cole, T, Hodgson, S, Godwin, AK, Stoppa-Lyonnet, D, Buecher, B, Léoné, M, Bressac-de Paillerets, B, Remenieras, A, Caron, O, Lenoir, GM, Sevenet, N, Longy, M, Ferrer, SF, Prieur, F, Goldgar, D, Miron, A, John, EM, Buys, SS, Daly, MB, Hopper, JL, Terry, MB, Yassin, Y, Singer, C, Gschwantler-Kaulich, D, Staudigl, C, Hansen, TVO, Barkardottir, RB, Kirchhoff, T, Pal, P, Kosarin, K, Offit, K, Piedmonte, M, Rodriguez, GC, Wakeley, K, Boggess, JF, Basil, J, Schwartz, PE, Blank, SV, Toland, AE, Montagna, M, Casella, C, Imyanitov, EN, Allavena, A, Schmutzler, RK, Versmold, B, Engel, C, Meindl, A, Ditsch, N, Arnold, N, Niederacher, D, Deissler, H, Fiebig, B, Suttner, C, Schönbuchner, I, Gadzicki, D, Caldes, T, de la Hoya, M, Pooley, KA, Easton, DF & Chenevix-Trench, G 2009, 'Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers', Human Molecular Genetics. https://doi.org/10.1093/hmg/ddp372

TY - JOUR

T1 - Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers

AU - Antoniou, Antonis C

AU - Sinilnikova, Olga M

AU - McGuffog, Lesley

AU - Healey, Sue

AU - Nevanlinna, Heli

AU - Heikkinen, Tuomas

AU - Simard, Jacques

AU - Spurdle, Amanda B

AU - Beesley, Jonathan

AU - Chen, Xiaoqing

AU - Neuhausen, Susan L

AU - Ding, Yuan C

AU - Couch, Fergus J

AU - Wang, Xianshu

AU - Fredericksen, Zachary

AU - Peterlongo, Paolo

AU - Peissel, Bernard

AU - Bonanni, Bernardo

AU - Viel, Alessandra

AU - Bernard, Loris

AU - Radice, Paolo

AU - Szabo, Csilla I

AU - Foretova, Lenka

AU - Zikan, Michal

AU - Claes, Kathleen

AU - Greene, Mark H

AU - Mai, Phuong L

AU - Rennert, Gad

AU - Lejbkowicz, Flavio

AU - Andrulis, Irene L

AU - Ozcelik, Hilmi

AU - Glendon, Gord

AU - Gerdes, Anne-Marie

AU - Thomassen, Mads

AU - Sunde, Lone

AU - Caligo, Maria A

AU - Laitman, Yael

AU - Kontorovich, Tair

AU - Cohen, Shimrit

AU - Kaufman, Bella

AU - Dagan, Efrat

AU - Baruch, Ruth Gershoni

AU - Friedman, Eitan

AU - Harbst, Katja

AU - Barbany-Bustinza, Gisela

AU - Rantala, Johanna

AU - Ehrencrona, Hans

AU - Karlsson, Per

AU - Domchek, Susan M

AU - Nathanson, Katherine L

AU - Osorio, Ana

AU - Blanco, Ignacio

AU - Lasa, Adriana

AU - Benítez, Javier

AU - Hamann, Ute

AU - Hogervorst, Frans B L

AU - Rookus, Matti A

AU - Collee, J Margriet

AU - Devilee, Peter

AU - Ligtenberg, Marjolijn J

AU - van der Luijt, Rob B

AU - Aalfs, Cora M

AU - Waisfisz, Quinten

AU - Wijnen, Juul

AU - van Roozendaal, Cornelis E P

AU - Peock, Susan

AU - Cook, Margaret

AU - Frost, Debra

AU - Oliver, Clare

AU - Platte, Radka

AU - Evans, D Gareth

AU - Lalloo, Fiona

AU - Eeles, Rosalind

AU - Izatt, Louise

AU - Davidson, Rosemarie

AU - Chu, Carol

AU - Eccles, Diana

AU - Cole, Trevor

AU - Hodgson, Shirley

AU - Godwin, Andrew K

AU - Stoppa-Lyonnet, Dominique

AU - Buecher, Bruno

AU - Léoné, Mélanie

AU - Bressac-de Paillerets, Brigitte

AU - Remenieras, Audrey

AU - Caron, Olivier

AU - Lenoir, Gilbert M

AU - Sevenet, Nicolas

AU - Longy, Michel

AU - Ferrer, Sandra Fert

AU - Prieur, Fabienne

AU - Goldgar, David

AU - Miron, Alexander

AU - John, Esther M

AU - Buys, Saundra S

AU - Daly, Mary B

AU - Hopper, John L

AU - Terry, Mary Beth

AU - Yassin, Yosuf

AU - Singer, Christian

AU - Gschwantler-Kaulich, Daphne

AU - Staudigl, Christine

AU - Hansen, Thomas v O

AU - Barkardottir, Rosa Bjork

AU - Kirchhoff, Tomas

AU - Pal, Prodipto

AU - Kosarin, Kristi

AU - Offit, Kenneth

AU - Piedmonte, Marion

AU - Rodriguez, Gustavo C

AU - Wakeley, Katie

AU - Boggess, John F

AU - Basil, Jack

AU - Schwartz, Peter E

AU - Blank, Stephanie V

AU - Toland, Amanda E

AU - Montagna, Marco

AU - Casella, Cinzia

AU - Imyanitov, Evgeny N

AU - Allavena, Anna

AU - Schmutzler, Rita K

AU - Versmold, Beatrix

AU - Engel, Christoph

AU - Meindl, Alfons

AU - Ditsch, Nina

AU - Arnold, Norbert

AU - Niederacher, Dieter

AU - Deissler, Helmut

AU - Fiebig, Britta

AU - Suttner, Christian

AU - Schönbuchner, Ines

AU - Gadzicki, Dorothea

AU - Caldes, Trinidad

AU - de la Hoya, Miguel

AU - Pooley, Karen A

AU - Easton, Douglas F

AU - Chenevix-Trench, Georgia

PY - 2009/11/15

Y1 - 2009/11/15

N2 - Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 x 10(-4)]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not.

AB - Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 x 10(-4)]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - BRCA1 Protein

KW - BRCA2 Protein

KW - Breast Neoplasms

KW - Chromosomes, Human, Pair 2

KW - Chromosomes, Human, Pair 8

KW - Female

KW - Follow-Up Studies

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Genetics, Population

KW - Genome-Wide Association Study

KW - Heterozygote

KW - Humans

KW - Microfilament Proteins

KW - Middle Aged

KW - Mutation

KW - Polymorphism, Single Nucleotide

KW - Young Adult

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - BRCA1 Protein

KW - BRCA2 Protein

KW - Breast Neoplasms

KW - Chromosomes, Human, Pair 2

KW - Chromosomes, Human, Pair 8

KW - Female

KW - Follow-Up Studies

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Genetics, Population

KW - Genome-Wide Association Study

KW - Heterozygote

KW - Humans

KW - Microfilament Proteins

KW - Middle Aged

KW - Mutation

KW - Polymorphism, Single Nucleotide

KW - Young Adult

U2 - 10.1093/hmg/ddp372

DO - 10.1093/hmg/ddp372

M3 - Article

C2 - 19656774

SN - 0964-6906

JO - Human Molecular Genetics

JF - Human Molecular Genetics

ER -

Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers

Abstract

Other keywords

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