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

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Garcia-Closas, Montserrat (author)

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

Article/chapterEnglish2008

Publisher, publication year, extent ...

2008-04-25
Public Library of Science (PLoS),2008
printrdacarrier

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LIBRIS-ID:oai:DiVA.org:uu-105393
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-105393URI
https://doi.org/10.1371/journal.pgen.1000054DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:116961299URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

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.

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MEDICINE
MEDICIN

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Hall, PerKarolinska Institutet (author)
Nevanlinna, Heli (author)
Pooley, Karen (author)
Morrison, Jonathan (author)
Richesson, Douglas A. (author)
Bojesen, Stig E. (author)
Nordestgaard, Børge G. (author)
Axelsson, Christen K. (author)
Arias, Jose I. (author)
Milne, Roger L. (author)
Ribas, Gloria (author)
González-Neira, Anna (author)
Benítez, Javier (author)
Zamora, Pilar (author)
Brauch, Hiltrud (author)
Justenhoven, Christina (author)
Hamann, Ute (author)
Ko, Yon-Dschun (author)
Bruening, Thomas (author)
Haas, Susanne (author)
Dörk, Thilo (author)
Schürmann, Peter (author)
Hillemanns, Peter (author)
Bogdanova, Natalia (author)
Bremer, Michael (author)
Karstens, Johann Hinrich (author)
Fagerholm, Rainer (author)
Aaltonen, Kirsimari (author)
Aittomäki, Kristiina (author)
von Smitten, Karl (author)
Blomqvist, CarlUppsala universitet,Enheten för onkologi (author)
Mannermaa, Arto (author)
Uusitupa, Matti (author)
Eskelinen, Matti (author)
Tengström, Maria (author)
Kosma, Veli-Matti (author)
Kataja, Vesa (author)
Chenevix-Trench, Georgia (author)
Spurdle, Amanda B. (author)
Beesley, Jonathan (author)
Chen, Xiaoqing (author)
Australian Ovarian Cancer Management Group, (author)
Kathleen Cuningham Foundation Consortium For Research Into Familial Breast Cancer, (author)
Devilee, Peter (author)
van Asperen, Christi J. (author)
Jacobi, Catharina E. (author)
Tollenaar, Rob A. E. M. (author)
Huijts, Petra E. A. (author)
Klijn, Jan G. M. (author)
Chang-Claude, Jenny (author)
Kropp, Silke (author)
Slanger, Tracy (author)
Flesch-Janys, Dieter (author)
Mutschelknauss, Elke (author)
Salazar, Ramona (author)
Wang-Gohrke, Shan (author)
Couch, Fergus (author)
Goode, Ellen L. (author)
Olson, Janet E. (author)
Vachon, Celine (author)
Fredericksen, Zachary S. (author)
Giles, Graham G. (author)
Baglietto, Laura (author)
Severi, Gianluca (author)
Hopper, John L. (author)
English, Dallas R. (author)
Southey, Melissa C. (author)
Haiman, Christopher A. (author)
Henderson, Brian E. (author)
Kolonel, Laurence N. (author)
Le Marchand, Loic (author)
Stram, Daniel O. (author)
Hunter, David J. (author)
Hankinson, Susan E. (author)
Cox, David G. (author)
Tamimi, Rulla (author)
Kraft, Peter (author)
Sherman, Mark E. (author)
Chanock, Stephen J. (author)
Lissowska, Jolanta (author)
Brinton, Louise A. (author)
Peplonska, Beata (author)
Klijn, Jan G. M. (author)
Hooning, Maartje J. (author)
Meijers-Heijboer, Han (author)
Collee, J. Margriet (author)
van den Ouweland, Ans (author)
Uitterlinden, Andre G. (author)
Liu, Jianjun (author)
Lin, Low Yen (author)
Yuqing, Li (author)
Humphreys, KeithKarolinska Institutet (author)
Czene, KamilaKarolinska Institutet (author)
Cox, Angela (author)
Balasubramanian, Sabapathy P. (author)
Cross, Simon S. (author)
Reed, Malcolm W. R. (author)
Blows, Fiona (author)
Driver, Kristy (author)
Dunning, Alison (author)
Tyrer, Jonathan (author)
Ponder, Bruce A. J. (author)
Sangrajrang, Suleeporn (author)
Brennan, Paul (author)
McKay, James (author)
Odefrey, Fabrice (author)
Gabrieau, Valerie (author)
Sigurdson, Alice (author)
Doody, Michele (author)
Struewing, Jeffrey P. (author)
Alexander, Bruce (author)
Easton, Douglas F. (author)
Pharoah, Paul D. (author)
Karolinska InstitutetEnheten för onkologi (creator_code:org_t)

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In:PLoS genetics: Public Library of Science (PLoS)4:4, s. e1000054-1553-7404

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By the author/editor: Garcia-Closas, M ...; Hall, Per; Nevanlinna, Heli; Pooley, Karen; Morrison, Jonath ...; Richesson, Dougl ...; show more...; Bojesen, Stig E.; Nordestgaard, Bø ...; Axelsson, Christ ...; Arias, Jose I.; Milne, Roger L.; Ribas, Gloria; González-Neira, ...; Benítez, Javier; Zamora, Pilar; Brauch, Hiltrud; Justenhoven, Chr ...; Hamann, Ute; Ko, Yon-Dschun; Bruening, Thomas; Haas, Susanne; Dörk, Thilo; Schürmann, Peter; Hillemanns, Pete ...; Bogdanova, Natal ...; Bremer, Michael; Karstens, Johann ...; Fagerholm, Raine ...; Aaltonen, Kirsim ...; Aittomäki, Krist ...; von Smitten, Kar ...; Blomqvist, Carl; Mannermaa, Arto; Uusitupa, Matti; Eskelinen, Matti; Tengström, Maria; Kosma, Veli-Matt ...; Kataja, Vesa; Chenevix-Trench, ...; Spurdle, Amanda ...; Beesley, Jonatha ...; Chen, Xiaoqing; Australian Ovari ...; Kathleen Cuningh ...; Devilee, Peter; van Asperen, Chr ...; Jacobi, Catharin ...; Tollenaar, Rob A ...; Huijts, Petra E. ...; Klijn, Jan G. M.; Chang-Claude, Je ...; Kropp, Silke; Slanger, Tracy; Flesch-Janys, Di ...; Mutschelknauss, ...; Salazar, Ramona; Wang-Gohrke, Sha ...; Couch, Fergus; Goode, Ellen L.; Olson, Janet E.; Vachon, Celine; Fredericksen, Za ...; Giles, Graham G.; Baglietto, Laura; Severi, Gianluca; Hopper, John L.; English, Dallas ...; Southey, Melissa ...; Haiman, Christop ...; Henderson, Brian ...; Kolonel, Laurenc ...; Le Marchand, Loi ...; Stram, Daniel O.; Hunter, David J.; Hankinson, Susan ...; Cox, David G.; Tamimi, Rulla; Kraft, Peter; Sherman, Mark E.; Chanock, Stephen ...; Lissowska, Jolan ...; Brinton, Louise ...; Peplonska, Beata; Hooning, Maartje ...; Meijers-Heijboer ...; Collee, J. Margr ...; van den Ouweland ...; Uitterlinden, An ...; Liu, Jianjun; Lin, Low Yen; Yuqing, Li; Humphreys, Keith; Czene, Kamila; Cox, Angela; Balasubramanian, ...; Cross, Simon S.; Reed, Malcolm W. ...; Blows, Fiona; Driver, Kristy; Dunning, Alison; Tyrer, Jonathan; Ponder, Bruce A. ...; Sangrajrang, Sul ...; Brennan, Paul; McKay, James; Odefrey, Fabrice; Gabrieau, Valeri ...; Sigurdson, Alice; Doody, Michele; Struewing, Jeffr ...; Alexander, Bruce; Easton, Douglas ...; Pharoah, Paul D.; show less...

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