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

被引：301

作者：

Garcia-Closas, Montserrat ^{[1
]}

Hall, Per ^{[2
]}

Nevanlinna, Heli ^{[3
]}

Pooley, Karen ^{[4
]}

Morrison, Jonathan ^{[4
]}

Richesson, Douglas A.

Bojesen, Stig E. ^{[5
,6
]}

Nordestgaard, Borge G.

Axelsson, Christen K. ^{[7
]}

Arias, Jose I. ^{[8
,9
]}

Milne, Roger L. ^{[8
]}

Ribas, Gloria ^{[8
]}

Gonzalez-Neira, Anna ^{[8
]}

Benitez, Javier ^{[8
]}

Zamora, Pilar ^{[10
]}

Brauch, Hiltrud ^{[11
]}

Justenhoven, Christina ^{[11
]}

Hamann, Ute ^{[12
]}

Ko, Yon-Dschun ^{[13
]}

Bruening, Thomas ^{[14
]}

Haas, Susanne ^{[15
]}

Doerk, Thilo ^{[16
]}

Schuermann, Peter ^{[16
]}

Hillemanns, Peter ^{[16
]}

Bogdanova, Natalia ^{[16
,17
]}

Bremer, Michael ^{[17
]}

Karstens, Johann Hinrich ^{[17
]}

Fagerholm, Rainer

Aaltonen, Kirsimari ^{[18
]}

Aittomaki, Kristiina ^{[19
]}

Von Smitten, Karl ^{[20
]}

Blomqvist, Carl

Mannermaa, Arto ^{[21
,22
]}

Uusitupa, Matti ^{[23
]}

Eskelinen, Matti ^{[24
]}

Tengstrom, Maria ^{[25
]}

Kosma, Veli-Matti

Kataja, Vesa ^{[25
,26
]}

Chenevix-Trench, Georgia ^{[27
]}

Spurdle, Amanda B. ^{[27
]}

Beesley, Jonathan ^{[27
]}

Chen, Xiaoqing ^{[27
]}

Devilee, Peter ^{[29
]}

Van Asperen, Christi J. ^{[30
]}

Jacobi, Catharina E. ^{[31
]}

Tollenaar, Rob A. E. M. ^{[32
]}

Huijts, Petra E. A. ^{[33
]}

Klijn, Jan G. M. ^{[33
,53
]}

Chang-Claude, Jenny ^{[34
]}

Kropp, Silke ^{[34
]}

机构：

[1] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA

[2] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[3] Univ Helsinki, Cent Hosp, Dept Obstet & Gynaecol, Helsinki, Finland

[4] Univ Cambridge, Dept Oncol, Cambridge, England

[5] Univ Copenhagen, Dept Clin Biochem, Herlev & Bispebjerg Univ Hosp, DK-1168 Copenhagen, Denmark

[6] Univ Copenhagen, Dept Bispebjerg Univ Hosp, DK-1168 Copenhagen, Denmark

[7] Univ Copenhagen, Herlev Univ Hosp, Dept Breast Surg, DK-1168 Copenhagen, Denmark

[8] Spanish Natl Canc Ctr, Madrid, Spain

[9] Montel Naraco Hosp, Oviedo, Spain

[10] Hosp La Paz, Madrid, Spain

[11] Stuttgart & Univ Tubingen, Dr Margarete Fischer Bosch Inst Clin Pharmacol, Tubingen, Germany

[12] Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany

[13] Evangel Klin Bonn gGmhH Johanniter Krankenhaus, Bonn, Germany

[14] Ruhr Univ Bochum, Berufgenossenschaft Forsch Inst Arbeits Med, Bochum, Germany

[15] Univ Bonn, Inst Pathol, D-5300 Bonn, Germany

[16] Hannover Med Sch, Dept Gynecol & Obstet, D-3000 Hannover, Germany

[17] Hannover Med Sch, Dept Radiat Oncol, D-3000 Hannover, Germany

[18] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland

[19] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland

[20] Univ Helsinki, Cent Hosp, Dept Surg, Helsinki, Finland

[21] Univ Kuopio, Bioctr Kuopio, Inst Clin Med Pathol & Forens Med, FIN-70211 Kuopio, Finland

[22] Kuopio Univ Hosp, Dept Pathol, SF-70210 Kuopio, Finland

[23] Univ Kuopio, Bioctr Kuopio, Dept Publ Hlth & Clin Nutr, FIN-70211 Kuopio, Finland

[24] Kuopio Univ Hosp, Dept Surg, SF-70210 Kuopio, Finland

[25] Kuopio Univ Hosp, Dept Oncol, SF-70210 Kuopio, Finland

[26] Vaasa Cent Hosp, Dept Oncol, Vaasa, Finland

[27] Royal Brisbane Hosp, Queensland Inst Med Res Post Off, Herston, Qld, Australia

[28] Peter MacCallum Canc Inst, Melbourne, Vic, Australia

[29] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands

[30] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands

[31] Leiden Univ, Med Ctr, Dept Med Decis Making, Leiden, Netherlands

[32] Leiden Univ, Med Ctr, Dept Surg, Leiden, Netherlands

[33] Erasmus MC Daniel Hoed Canc Ctr, Dept Med Oncol, Family Canc Clin, Rotterdam, Netherlands

[34] German Canc Res Ctr, Div Canc Epidemol, D-6900 Heidelberg, Germany

[35] Univ Clin Hamburg Eppendorf, Inst Med Biomet & Epidemol, Hamburg, Germany

[36] Bioglobe GmbH, Hamburg, Germany

[37] Univ Ulm, Dept Obstet & Gynecol, Mol Biol Lab, Ulm, Germany

[38] Mayo Clin, Coll Med, Rochester, MN USA

[39] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia

[40] Univ Melbourne, Ctr MEGA Epidemol, Melbourne, Vic, Australia

[41] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia

[42] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[43] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96822 USA

[44] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[45] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA

[46] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA

[47] Harvard Univ, Sch Med, Boston, MA 02115 USA

[48] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemol, Boston, MA 02115 USA

[49] Natl Canc Inst, Adv Technol Ctr, Gaithersburg, MD USA

[50] Ctr Canc, Dept Canc Epidemol & Prevent, Warsaw, Poland

来源：

PLOS GENETICS | 2008年 / 4卷 / 04期

关键词：

D O I：

10.1371/journal.pgen.1000054

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：10

共 30 条

[1]

ADNANE J, 1991, ONCOGENE, V6, P659

[2] The origins of estrogen receptor alpha-positive and estrogen receptor alpha-negative human breast cancer [J].

Allred, DC ;

Brown, P ;

Medina, D .

BREAST CANCER RESEARCH, 2004, 6 (06) :240-245

[3]

Althuis MD, 2004, CANCER EPIDEM BIOMAR, V13, P1558

[4] Distinct breast cancer incidence and prognostic patterns in the NCI's SEER program: suggesting a possible link between etiology and outcome [J].

Anderson, WF ;

Jatoi, I ;

Devesa, SS .

BREAST CANCER RESEARCH AND TREATMENT, 2005, 90 (02) :127-137

[5]

[Anonymous], 1993, Resampling-based multiple testing: Examples and methods for P-value adjustment

[6]

[Anonymous], CANC BIOL THER

[7] A crucial role for fibroblast growth factor signaling in embryonic mammary gland development [J].

Dillon, C ;

Spencer-Dene, B ;

Dickson, C .

JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA, 2004, 9 (02) :207-215

[8] Genome-wide association study identifies novel breast cancer susceptibility loci [J].

Easton, Douglas F. ;

Pooley, Karen A. ;

Dunning, Alison M. ;

Pharoah, Paul D. P. ;

Thompson, Deborah ;

Ballinger, Dennis G. ;

Struewing, Jeffery P. ;

Morrison, Jonathan ;

Field, Helen ;

Luben, Robert ;

Wareham, Nicholas ;

Ahmed, Shahana ;

Healey, Catherine S. ;

Bowman, Richard ;

Meyer, Kerstin B. ;

Haiman, Christopher A. ;

Kolonel, Laurence K. ;

Henderson, Brian E. ;

Le Marchand, Loic ;

Brennan, Paul ;

Sangrajrang, Suleeporn ;

Gaborieau, Valerie ;

Odefrey, Fabrice ;

Shen, Chen-Yang ;

Wu, Pei-Ei ;

Wang, Hui-Chun ;

Eccles, Diana ;

Evans, D. Gareth ;

Peto, Julian ;

Fletcher, Olivia ;

Johnson, Nichola ;

Seal, Sheila ;

Stratton, Michael R. ;

Rahman, Nazneen ;

Chenevix-Trench, Georgia ;

Bojesen, Stig E. ;

Nordestgaard, Borge G. ;

Axelsson, Christen K. ;

Garcia-Closas, Montserrat ;

Brinton, Louise ;

Chanock, Stephen ;

Lissowska, Jolanta ;

Peplonska, Beata ;

Nevanlinna, Heli ;

Fagerholm, Rainer ;

Eerola, Hannaleena ;

Kang, Daehee ;

Yoo, Keun-Young ;

Noh, Dong-Young ;

Ahn, Sei-Hyun .

NATURE, 2007, 447 (7148) :1087-U7

[9] Fibroblast growth factor signaling in tumorigenesis [J].

Grose, R ;

Dickson, C .

CYTOKINE & GROWTH FACTOR REVIEWS, 2005, 16 (02) :179-186

[10] Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24 [J].

Gudmundsson, Julius ;

Sulem, Patrick ;

Manolescu, Andrei ;

Amundadottir, Laufey T. ;

Gudbjartsson, Daniel ;

Helgason, Agnar ;

Rafnar, Thorunn ;

Bergthorsson, Jon T. ;

Agnarsson, Bjarni A. ;

Baker, Adam ;

Sigurdsson, Asgeir ;

Benediktsdottir, Kristrun R. ;

Jakobsdottir, Margret ;

Xu, Jianfeng ;

Blondal, Thorarinn ;

Kostic, Jelena ;

Sun, Jielin ;

Ghosh, Shyamali ;

Stacey, Simon N. ;

Mouy, Magali ;

Saemundsdottir, Jona ;

Backman, Valgerdur M. ;

Kristjansson, Kristleifur ;

Tres, Alejandro ;

Partin, Alan W. ;

Albers-Akkers, Marjo T. ;

Marcos, Javier Godino-Ivan ;

Walsh, Patrick C. ;

Swinkels, Dorine W. ;

Navarrete, Sebastian ;

Isaacs, Sarah D. ;

Aben, Katja K. ;

Graif, Theresa ;

Cashy, John ;

Ruiz-Echarri, Manuel ;

Wiley, Kathleen E. ;

Suarez, Brian K. ;

Witjes, J. Alfred ;

Frigge, Mike ;

Ober, Carole ;

Jonsson, Eirikur ;

Einarsson, Gudmundur V. ;

Mayordomo, Jose I. ;

Kiemeney, Lambertus A. ;

Isaacs, William B. ;

Catalona, William J. ;

Barkardottir, Rosa B. ;

Gulcher, Jeffrey R. ;

Thorsteinsdottir, Unnur ;

Kong, Augustine .

NATURE GENETICS, 2007, 39 (05) :631-637

← 1 2 3 →