Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics.
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)) associ...
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2008
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Genetics QH426-470 |
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Genetics QH426-470 Montserrat Garcia-Closas Per Hall Heli Nevanlinna Karen Pooley Jonathan Morrison Douglas A Richesson Stig E Bojesen Børge G Nordestgaard Christen K Axelsson Jose I Arias Roger L Milne Gloria Ribas Anna González-Neira Javier Benítez Pilar Zamora Hiltrud Brauch Christina Justenhoven Ute Hamann Yon-Dschun Ko Thomas Bruening Susanne Haas Thilo Dörk Peter Schürmann Peter Hillemanns Natalia Bogdanova Michael Bremer Johann Hinrich Karstens Rainer Fagerholm Kirsimari Aaltonen Kristiina Aittomäki Karl von Smitten Carl Blomqvist Arto Mannermaa Matti Uusitupa Matti Eskelinen Maria Tengström Veli-Matti Kosma Vesa Kataja Georgia Chenevix-Trench Amanda B Spurdle Jonathan Beesley Xiaoqing Chen Australian Ovarian Cancer Management Group Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer Peter Devilee Christi J van Asperen Catharina E Jacobi Rob A E M Tollenaar Petra E A Huijts Jan G M Klijn Jenny Chang-Claude Silke Kropp Tracy Slanger Dieter Flesch-Janys Elke Mutschelknauss Ramona Salazar Shan Wang-Gohrke Fergus Couch Ellen L Goode Janet E Olson Celine Vachon Zachary S Fredericksen Graham G Giles Laura Baglietto Gianluca Severi John L Hopper Dallas R English Melissa C Southey Christopher A Haiman Brian E Henderson Laurence N Kolonel Loic Le Marchand Daniel O Stram David J Hunter Susan E Hankinson David G Cox Rulla Tamimi Peter Kraft Mark E Sherman Stephen J Chanock Jolanta Lissowska Louise A Brinton Beata Peplonska Jan G M Klijn Maartje J Hooning Han Meijers-Heijboer J Margriet Collee Ans van den Ouweland Andre G Uitterlinden Jianjun Liu Low Yen Lin Li Yuqing Keith Humphreys Kamila Czene Angela Cox Sabapathy P Balasubramanian Simon S Cross Malcolm W R Reed Fiona Blows Kristy Driver Alison Dunning Jonathan Tyrer Bruce A J Ponder Suleeporn Sangrajrang Paul Brennan James McKay Fabrice Odefrey Valerie Gabrieau Alice Sigurdson Michele Doody Jeffrey P Struewing Bruce Alexander Douglas F Easton Paul D Pharoah Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. |
| description |
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. |
| format |
article |
| author |
Montserrat Garcia-Closas Per Hall Heli Nevanlinna Karen Pooley Jonathan Morrison Douglas A Richesson Stig E Bojesen Børge G Nordestgaard Christen K Axelsson Jose I Arias Roger L Milne Gloria Ribas Anna González-Neira Javier Benítez Pilar Zamora Hiltrud Brauch Christina Justenhoven Ute Hamann Yon-Dschun Ko Thomas Bruening Susanne Haas Thilo Dörk Peter Schürmann Peter Hillemanns Natalia Bogdanova Michael Bremer Johann Hinrich Karstens Rainer Fagerholm Kirsimari Aaltonen Kristiina Aittomäki Karl von Smitten Carl Blomqvist Arto Mannermaa Matti Uusitupa Matti Eskelinen Maria Tengström Veli-Matti Kosma Vesa Kataja Georgia Chenevix-Trench Amanda B Spurdle Jonathan Beesley Xiaoqing Chen Australian Ovarian Cancer Management Group Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer Peter Devilee Christi J van Asperen Catharina E Jacobi Rob A E M Tollenaar Petra E A Huijts Jan G M Klijn Jenny Chang-Claude Silke Kropp Tracy Slanger Dieter Flesch-Janys Elke Mutschelknauss Ramona Salazar Shan Wang-Gohrke Fergus Couch Ellen L Goode Janet E Olson Celine Vachon Zachary S Fredericksen Graham G Giles Laura Baglietto Gianluca Severi John L Hopper Dallas R English Melissa C Southey Christopher A Haiman Brian E Henderson Laurence N Kolonel Loic Le Marchand Daniel O Stram David J Hunter Susan E Hankinson David G Cox Rulla Tamimi Peter Kraft Mark E Sherman Stephen J Chanock Jolanta Lissowska Louise A Brinton Beata Peplonska Jan G M Klijn Maartje J Hooning Han Meijers-Heijboer J Margriet Collee Ans van den Ouweland Andre G Uitterlinden Jianjun Liu Low Yen Lin Li Yuqing Keith Humphreys Kamila Czene Angela Cox Sabapathy P Balasubramanian Simon S Cross Malcolm W R Reed Fiona Blows Kristy Driver Alison Dunning Jonathan Tyrer Bruce A J Ponder Suleeporn Sangrajrang Paul Brennan James McKay Fabrice Odefrey Valerie Gabrieau Alice Sigurdson Michele Doody Jeffrey P Struewing Bruce Alexander Douglas F Easton Paul D Pharoah |
| author_facet |
Montserrat Garcia-Closas Per Hall Heli Nevanlinna Karen Pooley Jonathan Morrison Douglas A Richesson Stig E Bojesen Børge G Nordestgaard Christen K Axelsson Jose I Arias Roger L Milne Gloria Ribas Anna González-Neira Javier Benítez Pilar Zamora Hiltrud Brauch Christina Justenhoven Ute Hamann Yon-Dschun Ko Thomas Bruening Susanne Haas Thilo Dörk Peter Schürmann Peter Hillemanns Natalia Bogdanova Michael Bremer Johann Hinrich Karstens Rainer Fagerholm Kirsimari Aaltonen Kristiina Aittomäki Karl von Smitten Carl Blomqvist Arto Mannermaa Matti Uusitupa Matti Eskelinen Maria Tengström Veli-Matti Kosma Vesa Kataja Georgia Chenevix-Trench Amanda B Spurdle Jonathan Beesley Xiaoqing Chen Australian Ovarian Cancer Management Group Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer Peter Devilee Christi J van Asperen Catharina E Jacobi Rob A E M Tollenaar Petra E A Huijts Jan G M Klijn Jenny Chang-Claude Silke Kropp Tracy Slanger Dieter Flesch-Janys Elke Mutschelknauss Ramona Salazar Shan Wang-Gohrke Fergus Couch Ellen L Goode Janet E Olson Celine Vachon Zachary S Fredericksen Graham G Giles Laura Baglietto Gianluca Severi John L Hopper Dallas R English Melissa C Southey Christopher A Haiman Brian E Henderson Laurence N Kolonel Loic Le Marchand Daniel O Stram David J Hunter Susan E Hankinson David G Cox Rulla Tamimi Peter Kraft Mark E Sherman Stephen J Chanock Jolanta Lissowska Louise A Brinton Beata Peplonska Jan G M Klijn Maartje J Hooning Han Meijers-Heijboer J Margriet Collee Ans van den Ouweland Andre G Uitterlinden Jianjun Liu Low Yen Lin Li Yuqing Keith Humphreys Kamila Czene Angela Cox Sabapathy P Balasubramanian Simon S Cross Malcolm W R Reed Fiona Blows Kristy Driver Alison Dunning Jonathan Tyrer Bruce A J Ponder Suleeporn Sangrajrang Paul Brennan James McKay Fabrice Odefrey Valerie Gabrieau Alice Sigurdson Michele Doody Jeffrey P Struewing Bruce Alexander Douglas F Easton Paul D Pharoah |
| author_sort |
Montserrat Garcia-Closas |
| title |
Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. |
| title_short |
Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. |
| title_full |
Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. |
| title_fullStr |
Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. |
| title_full_unstemmed |
Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. |
| title_sort |
heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2008 |
| url |
https://doaj.org/article/d83899862e5c4f17a6111d8afac72371 |
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oai:doaj.org-article:d83899862e5c4f17a6111d8afac723712021-12-02T20:03:12ZHeterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics.1553-73901553-740410.1371/journal.pgen.1000054https://doaj.org/article/d83899862e5c4f17a6111d8afac723712008-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18437204/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404A 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.Montserrat Garcia-ClosasPer HallHeli NevanlinnaKaren PooleyJonathan MorrisonDouglas A RichessonStig E BojesenBørge G NordestgaardChristen K AxelssonJose I AriasRoger L MilneGloria RibasAnna González-NeiraJavier BenítezPilar ZamoraHiltrud BrauchChristina JustenhovenUte HamannYon-Dschun KoThomas BrueningSusanne HaasThilo DörkPeter SchürmannPeter HillemannsNatalia BogdanovaMichael BremerJohann Hinrich KarstensRainer FagerholmKirsimari AaltonenKristiina AittomäkiKarl von SmittenCarl BlomqvistArto MannermaaMatti UusitupaMatti EskelinenMaria TengströmVeli-Matti KosmaVesa KatajaGeorgia Chenevix-TrenchAmanda B SpurdleJonathan BeesleyXiaoqing ChenAustralian Ovarian Cancer Management GroupKathleen Cuningham Foundation Consortium for Research into Familial Breast CancerPeter DevileeChristi J van AsperenCatharina E JacobiRob A E M TollenaarPetra E A HuijtsJan G M KlijnJenny Chang-ClaudeSilke KroppTracy SlangerDieter Flesch-JanysElke MutschelknaussRamona SalazarShan Wang-GohrkeFergus CouchEllen L GoodeJanet E OlsonCeline VachonZachary S FredericksenGraham G GilesLaura BagliettoGianluca SeveriJohn L HopperDallas R EnglishMelissa C SoutheyChristopher A HaimanBrian E HendersonLaurence N KolonelLoic Le MarchandDaniel O StramDavid J HunterSusan E HankinsonDavid G CoxRulla TamimiPeter KraftMark E ShermanStephen J ChanockJolanta LissowskaLouise A BrintonBeata PeplonskaJan G M KlijnMaartje J HooningHan Meijers-HeijboerJ Margriet ColleeAns van den OuwelandAndre G UitterlindenJianjun LiuLow Yen LinLi YuqingKeith HumphreysKamila CzeneAngela CoxSabapathy P BalasubramanianSimon S CrossMalcolm W R ReedFiona BlowsKristy DriverAlison DunningJonathan TyrerBruce A J PonderSuleeporn SangrajrangPaul BrennanJames McKayFabrice OdefreyValerie GabrieauAlice SigurdsonMichele DoodyJeffrey P StruewingBruce AlexanderDouglas F EastonPaul D PharoahPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 4, Iss 4, p e1000054 (2008) |