Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics

M. Garcia-Closas; P. Hall; H. Nevanlinna; K. Pooley; J. Morrison; D.A. Richesson; S.E. Bojesen; C.K. Axelsson; J.I. Arias; R.L. Milne; G. Ribas; A. Gonzalez-Neira; J. Benitez; P. Zamora; H. Brauch; C. Justenhoven; U. Hamann; Y.D. Ko; T. Bruening; S. Haas; T. Dork; P. Schurmann; P. Hillemanns; N. Bogdanova; M. Bremer; J.H. Karstens; R. Fagerholm; K. Aaltonen; K. Aittomaki; K. Von Smitten; C. Blomqvist; A. Mannermaa; M. Uusitupa; M. Eskelinen; M. Tengstrom; V.M. Kosma; V. Kataja; G. Chenevix-Trench; A.B. Spurdle; J. Beesley; X. Chen; P. Devilee; C.J. Van Asperen; C.E. Jacobi; R.A.E.M. Tollenaar; P.E.A. Huijts; J.G.M. Klijn; J. Chang-Claude; S. Kropp; T. Slanger; D. Flesch-Janys; E. Mutschelknauss; R. Salazar; S. Wang-Gohrke; F. Couch; E.L. Goode; J.E. Olson; C. Vachon; Z.S. Fredericksen; G.G. Giles; L. Baglietto; G. Severi; J.L. Hopper; D.R. English; M.C. Southey; C.A. Haiman; B.E. Henderson; L.N. Kolonel; L. Le Marchand; D.O. Stram; D.J. Hunter; S.E. Hankinson; D.G. Cox; R. Tamimi; P. Kraft; M.E. Sherman; S.J. Chanock; J. Lissowska; L.A. Brinton; B. Peplonska; J.G.M. Klijn; M.J. Hooning; H. Meijers-Heijboer; J.M. Collee; A. Van den Ouweland; A.G. Uitterlinden; J. Liu; L.Y. Lin; L. Yuqing; K. Humphreys; K. Czene; A. Cox; S.P. Balasubramanian; S.S. Cross; M.W.R. Reed; F. Blows; K. Driver; A. Dunning; J. Tyrer; B.A.J. Ponder; S. Sangrajrang; P. Brennan; J. Mckay; F. Odefrey; V. Gabrieau; A. Sigurdson; M. Doody; J.P. Struewing; B. Alexander; D.F. Easton; P.D. Pharoah; Børge Nordestgaard

Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics

M. Garcia-Closas, P. Hall, H. Nevanlinna, K. Pooley, J. Morrison, D.A. Richesson, S.E. Bojesen, C.K. Axelsson, J.I. Arias, R.L. Milne, G. Ribas, A. Gonzalez-Neira, J. Benitez, P. Zamora, H. Brauch, C. Justenhoven, U. Hamann, Y.D. Ko, T. Bruening, S. HaasT. Dork, P. Schurmann, P. Hillemanns, N. Bogdanova, M. Bremer, J.H. Karstens, R. Fagerholm, K. Aaltonen, K. Aittomaki, K. Von Smitten, C. Blomqvist, A. Mannermaa, M. Uusitupa, M. Eskelinen, M. Tengstrom, V.M. Kosma, V. Kataja, G. Chenevix-Trench, A.B. Spurdle, J. Beesley, X. Chen, P. Devilee, C.J. Van Asperen, C.E. Jacobi, R.A.E.M. Tollenaar, P.E.A. Huijts, J.G.M. Klijn, J. Chang-Claude, S. Kropp, T. Slanger, D. Flesch-Janys, E. Mutschelknauss, R. Salazar, S. Wang-Gohrke, F. Couch, E.L. Goode, J.E. Olson, C. Vachon, Z.S. Fredericksen, G.G. Giles, L. Baglietto, G. Severi, J.L. Hopper, D.R. English, M.C. Southey, C.A. Haiman, B.E. Henderson, L.N. Kolonel, L. Le Marchand, D.O. Stram, D.J. Hunter, S.E. Hankinson, D.G. Cox, R. Tamimi, P. Kraft, M.E. Sherman, S.J. Chanock, J. Lissowska, L.A. Brinton, B. Peplonska, J.G.M. Klijn, M.J. Hooning, H. Meijers-Heijboer, J.M. Collee, A. Van den Ouweland, A.G. Uitterlinden, J. Liu, L.Y. Lin, L. Yuqing, K. Humphreys, K. Czene, A. Cox, S.P. Balasubramanian, S.S. Cross, M.W.R. Reed, F. Blows, K. Driver, A. Dunning, J. Tyrer, B.A.J. Ponder, S. Sangrajrang, P. Brennan, J. Mckay, F. Odefrey, V. Gabrieau, A. Sigurdson, M. Doody, J.P. Struewing, B. Alexander, D.F. Easton, P.D. Pharoah, Børge Nordestgaard

279 Citations (Scopus)

Abstract

A three-stage genome-wide association study recently identified single nucleotide polymorphisms ( SNPs) in five loci ( fibroblast growth receptor 2 ( FGFR2), trinucleotide repeat containing 9 ( TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte- specific protein 1 ( LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER- positive ( per- allele OR ( 95%CI) = 1.31 (1.27-1.36)) than ER- negative (1.08 (1.03- 1.14)) disease ( P for heterogeneity = 10-(13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER- positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs ( rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER- negative disease, the strongest association being for rs3803662 in TNRC9 ( 1.14 ( 1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis ( per- allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER- positive and ER- negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment
Udgivelsesdato: 2008/4

Original language	English
Journal	PLoS Genetics
Volume	4
Issue number	4
Pages (from-to)	-
ISSN	1553-7390
Publication status	Published - 2008

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Cite this

Garcia-Closas, M., Hall, P., Nevanlinna, H., Pooley, K., Morrison, J., Richesson, D. A., Bojesen, S. E., Axelsson, C. K., Arias, J. I., Milne, R. L., Ribas, G., Gonzalez-Neira, A., Benitez, J., Zamora, P., Brauch, H., Justenhoven, C., Hamann, U., Ko, Y. D., Bruening, T., ... Nordestgaard, B. (2008). Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. PLoS Genetics, 4(4), -.

Garcia-Closas, M, Hall, P, Nevanlinna, H, Pooley, K, Morrison, J, Richesson, DA, Bojesen, SE, Axelsson, CK, Arias, JI, Milne, RL, Ribas, G, Gonzalez-Neira, A, Benitez, J, Zamora, P, Brauch, H, Justenhoven, C, Hamann, U, Ko, YD, Bruening, T, Haas, S, Dork, T, Schurmann, P, Hillemanns, P, Bogdanova, N, Bremer, M, Karstens, JH, Fagerholm, R, Aaltonen, K, Aittomaki, K, Smitten, KV, Blomqvist, C, Mannermaa, A, Uusitupa, M, Eskelinen, M, Tengstrom, M, Kosma, VM, Kataja, V, Chenevix-Trench, G, Spurdle, AB, Beesley, J, Chen, X, Devilee, P, Asperen, CJV, Jacobi, CE, Tollenaar, RAEM, Huijts, PEA, Klijn, JGM, Chang-Claude, J, Kropp, S, Slanger, T, Flesch-Janys, D, Mutschelknauss, E, Salazar, R, Wang-Gohrke, S, Couch, F, Goode, EL, Olson, JE, Vachon, C, Fredericksen, ZS, Giles, GG, Baglietto, L, Severi, G, Hopper, JL, English, DR, Southey, MC, Haiman, CA, Henderson, BE, Kolonel, LN, Marchand, LL, Stram, DO, Hunter, DJ, Hankinson, SE, Cox, DG, Tamimi, R, Kraft, P, Sherman, ME, Chanock, SJ, Lissowska, J, Brinton, LA, Peplonska, B, Klijn, JGM, Hooning, MJ, Meijers-Heijboer, H, Collee, JM, Ouweland, AVD, Uitterlinden, AG, Liu, J, Lin, LY, Yuqing, L, Humphreys, K, Czene, K, Cox, A, Balasubramanian, SP, Cross, SS, Reed, MWR, Blows, F, Driver, K, Dunning, A, Tyrer, J, Ponder, BAJ, Sangrajrang, S, Brennan, P, Mckay, J, Odefrey, F, Gabrieau, V, Sigurdson, A, Doody, M, Struewing, JP, Alexander, B, Easton, DF, Pharoah, PD & Nordestgaard, B 2008, 'Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics', PLoS Genetics, vol. 4, no. 4, pp. -.

@article{3cc36a008c9c11de8bc9000ea68e967b,

title = "Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics",

abstract = "A three-stage genome-wide association study recently identified single nucleotide polymorphisms ( SNPs) in five loci ( fibroblast growth receptor 2 ( FGFR2), trinucleotide repeat containing 9 ( TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte- specific protein 1 ( LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER- positive ( per- allele OR ( 95%CI) = 1.31 (1.27-1.36)) than ER- negative (1.08 (1.03- 1.14)) disease ( P for heterogeneity = 10-(13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER- positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs ( rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER- negative disease, the strongest association being for rs3803662 in TNRC9 ( 1.14 ( 1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis ( per- allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER- positive and ER- negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment Udgivelsesdato: 2008/4",

author = "M. Garcia-Closas and P. Hall and H. Nevanlinna and K. Pooley and J. Morrison and D.A. Richesson and S.E. Bojesen and C.K. Axelsson and J.I. Arias and R.L. Milne and G. Ribas and A. Gonzalez-Neira and J. Benitez and P. Zamora and H. Brauch and C. Justenhoven and U. Hamann and Y.D. Ko and T. Bruening and S. Haas and T. Dork and P. Schurmann and P. Hillemanns and N. Bogdanova and M. Bremer and J.H. Karstens and R. Fagerholm and K. Aaltonen and K. Aittomaki and Smitten, {K. Von} and C. Blomqvist and A. Mannermaa and M. Uusitupa and M. Eskelinen and M. Tengstrom and V.M. Kosma and V. Kataja and G. Chenevix-Trench and A.B. Spurdle and J. Beesley and X. Chen and P. Devilee and Asperen, {C.J. Van} and C.E. Jacobi and R.A.E.M. Tollenaar and P.E.A. Huijts and J.G.M. Klijn and J. Chang-Claude and S. Kropp and T. Slanger and D. Flesch-Janys and E. Mutschelknauss and R. Salazar and S. Wang-Gohrke and F. Couch and E.L. Goode and J.E. Olson and C. Vachon and Z.S. Fredericksen and G.G. Giles and L. Baglietto and G. Severi and J.L. Hopper and D.R. English and M.C. Southey and C.A. Haiman and B.E. Henderson and L.N. Kolonel and Marchand, {L. Le} and D.O. Stram and D.J. Hunter and S.E. Hankinson and D.G. Cox and R. Tamimi and P. Kraft and M.E. Sherman and S.J. Chanock and J. Lissowska and L.A. Brinton and B. Peplonska and J.G.M. Klijn and M.J. Hooning and H. Meijers-Heijboer and J.M. Collee and Ouweland, {A. Van den} and A.G. Uitterlinden and J. Liu and L.Y. Lin and L. Yuqing and K. Humphreys and K. Czene and A. Cox and S.P. Balasubramanian and S.S. Cross and M.W.R. Reed and F. Blows and K. Driver and A. Dunning and J. Tyrer and B.A.J. Ponder and S. Sangrajrang and P. Brennan and J. Mckay and F. Odefrey and V. Gabrieau and A. Sigurdson and M. Doody and J.P. Struewing and B. Alexander and D.F. Easton and P.D. Pharoah and B{\o}rge Nordestgaard",

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journal = "P L o S Genetics",

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TY - JOUR

T1 - Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics

AU - Garcia-Closas, M.

AU - Hall, P.

AU - Nevanlinna, H.

AU - Pooley, K.

AU - Morrison, J.

AU - Richesson, D.A.

AU - Bojesen, S.E.

AU - Axelsson, C.K.

AU - Arias, J.I.

AU - Milne, R.L.

AU - Ribas, G.

AU - Gonzalez-Neira, A.

AU - Benitez, J.

AU - Zamora, P.

AU - Brauch, H.

AU - Justenhoven, C.

AU - Hamann, U.

AU - Ko, Y.D.

AU - Bruening, T.

AU - Haas, S.

AU - Dork, T.

AU - Schurmann, P.

AU - Hillemanns, P.

AU - Bogdanova, N.

AU - Bremer, M.

AU - Karstens, J.H.

AU - Fagerholm, R.

AU - Aaltonen, K.

AU - Aittomaki, K.

AU - Smitten, K. Von

AU - Blomqvist, C.

AU - Mannermaa, A.

AU - Uusitupa, M.

AU - Eskelinen, M.

AU - Tengstrom, M.

AU - Kosma, V.M.

AU - Kataja, V.

AU - Chenevix-Trench, G.

AU - Spurdle, A.B.

AU - Beesley, J.

AU - Chen, X.

AU - Devilee, P.

AU - Asperen, C.J. Van

AU - Jacobi, C.E.

AU - Tollenaar, R.A.E.M.

AU - Huijts, P.E.A.

AU - Klijn, J.G.M.

AU - Chang-Claude, J.

AU - Kropp, S.

AU - Slanger, T.

AU - Flesch-Janys, D.

AU - Mutschelknauss, E.

AU - Salazar, R.

AU - Wang-Gohrke, S.

AU - Couch, F.

AU - Goode, E.L.

AU - Olson, J.E.

AU - Vachon, C.

AU - Fredericksen, Z.S.

AU - Giles, G.G.

AU - Baglietto, L.

AU - Severi, G.

AU - Hopper, J.L.

AU - English, D.R.

AU - Southey, M.C.

AU - Haiman, C.A.

AU - Henderson, B.E.

AU - Kolonel, L.N.

AU - Marchand, L. Le

AU - Stram, D.O.

AU - Hunter, D.J.

AU - Hankinson, S.E.

AU - Cox, D.G.

AU - Tamimi, R.

AU - Kraft, P.

AU - Sherman, M.E.

AU - Chanock, S.J.

AU - Lissowska, J.

AU - Brinton, L.A.

AU - Peplonska, B.

AU - Klijn, J.G.M.

AU - Hooning, M.J.

AU - Meijers-Heijboer, H.

AU - Collee, J.M.

AU - Ouweland, A. Van den

AU - Uitterlinden, A.G.

AU - Liu, J.

AU - Lin, L.Y.

AU - Yuqing, L.

AU - Humphreys, K.

AU - Czene, K.

AU - Cox, A.

AU - Balasubramanian, S.P.

AU - Cross, S.S.

AU - Reed, M.W.R.

AU - Blows, F.

AU - Driver, K.

AU - Dunning, A.

AU - Tyrer, J.

AU - Ponder, B.A.J.

AU - Sangrajrang, S.

AU - Brennan, P.

AU - Mckay, J.

AU - Odefrey, F.

AU - Gabrieau, V.

AU - Sigurdson, A.

AU - Doody, M.

AU - Struewing, J.P.

AU - Alexander, B.

AU - Easton, D.F.

AU - Pharoah, P.D.

AU - Nordestgaard, Børge

N1 - Times Cited: 0ArticleEnglishGarcia-Closas, MNatl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USACited References Count: 30294LLPUBLIC LIBRARY SCIENCE185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USASAN FRANCISCO

PY - 2008

Y1 - 2008

N2 - A three-stage genome-wide association study recently identified single nucleotide polymorphisms ( SNPs) in five loci ( fibroblast growth receptor 2 ( FGFR2), trinucleotide repeat containing 9 ( TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte- specific protein 1 ( LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER- positive ( per- allele OR ( 95%CI) = 1.31 (1.27-1.36)) than ER- negative (1.08 (1.03- 1.14)) disease ( P for heterogeneity = 10-(13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER- positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs ( rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER- negative disease, the strongest association being for rs3803662 in TNRC9 ( 1.14 ( 1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis ( per- allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER- positive and ER- negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment Udgivelsesdato: 2008/4

AB - A three-stage genome-wide association study recently identified single nucleotide polymorphisms ( SNPs) in five loci ( fibroblast growth receptor 2 ( FGFR2), trinucleotide repeat containing 9 ( TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte- specific protein 1 ( LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER- positive ( per- allele OR ( 95%CI) = 1.31 (1.27-1.36)) than ER- negative (1.08 (1.03- 1.14)) disease ( P for heterogeneity = 10-(13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER- positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs ( rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER- negative disease, the strongest association being for rs3803662 in TNRC9 ( 1.14 ( 1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis ( per- allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER- positive and ER- negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment Udgivelsesdato: 2008/4

M3 - Journal article

SN - 1553-7390

VL - 4

SP - -

JO - P L o S Genetics

JF - P L o S Genetics

IS - 4

ER -