Ghoussaini, Maya, French, Juliet D., Michailidou, Kyriaki ORCID: 0000-0001-7065-1237, Nord, Silje ORCID: 0000-0002-3271-5356, Beesley, Jonathan ORCID: 0000-0003-1942-325X, Canisus, Sander, Hillman, Kristine M., Kaufmann, Susanne, Sivakumaran, Haran ORCID: 0000-0002-4691-4989, Marjaneh, Mandi Moradi, Lee, Jason S., Dennis, Joe, Bolla, Manjeet K., Wang, Qin, Dicks, Ed, Milne, Roger L., Hopper, John L., Southey, Melissa C., Schmidt, Marjanka K., Broeks, Annegien, Muir, Kenneth, Lophatananon, Artitaya, Fasching, Peter A., Beckmann, Matthias W., Fletcher, Olivia ORCID: 0000-0001-9387-7116, Johnson, Nichola, Sawyer, Elinor J., Tomlinson, Ian, Burwinkel, Barbara, Marme, Frederik, Guenel, Pascal ORCID: 0000-0002-8359-518X, Truong, Therese, Bojesen, Stig E., Flyger, Henrik, Benitez, Javier, Gonzalez-Neira, Anna ORCID: 0000-0002-5421-2020, Alonso, Rosario, Pita, Guillermo, Neuhausen, Susan L., Anton-Culver, Hoda, Brenner, Hermann ORCID: 0000-0002-6129-1572, Arndt, Volker ORCID: 0000-0001-9320-8684, Meindl, Alfons, Schmutzler, Rita K., Brauch, Hiltrud ORCID: 0000-0001-7531-2736, Hamann, Ute, Tessier, Daniel C., Vincent, Daniel, Nevanlinna, Heli, Khan, Sofia ORCID: 0000-0003-4185-8882, Matsuo, Keitaro ORCID: 0000-0003-1761-6314, Ito, Hidemi, Dork, Thilo ORCID: 0000-0002-9458-0282, Bogdanova, Natalia V., Lindblom, Annika, Margolin, Sara, Mannermaa, Arto, Kosma, Veli-Matti, Wu, Anna H., Van den Berg, David, Lambrechts, Diether ORCID: 0000-0002-3429-302X, Floris, Giuseppe, Chang-Claude, Jenny, Rudolph, Anja, Radice, Paolo ORCID: 0000-0001-6298-4111, Barile, Monica, Couch, Fergus J., Hallberg, Emily, Giles, Graham G., Haiman, Christopher A., Le Marchand, Loic, Goldberg, Mark S., Teo, Soo H., Yip, Cheng Har, Borresen-Dale, Anne-Lise, Zheng, Wei ORCID: 0000-0003-1226-070X, Cai, Qiuyin, Winqvist, Robert, Pylkas, Katri ORCID: 0000-0002-2449-0521, Andrulis, Irene L., Devilee, Peter ORCID: 0000-0002-8023-2009, Tollenaar, Rob A. E. M., Garcia-Closas, Montserrat, Figueroa, Jonine, Hall, Per, Czene, Kamila, Brand, Judith S. ORCID: 0000-0002-3720-1274, Darabi, Hatef, Eriksson, Mikael, Hooning, Maartje J., Koppert, Linetta B., Li, Jingmei ORCID: 0000-0001-8587-7511, Shu, Xiao-Ou, Zheng, Ying, Cox, Angela ORCID: 0000-0002-5138-1099, Cross, Simon S., Shah, Mitul, Rhenius, Valerie, Choi, Ji-Yeob, Kang, Daehee, Hartman, Mikael ORCID: 0000-0001-5726-9965, Chia, Kee Seng, Kabisch, Maria, Torres, Diana, Luccarini, Craig, Conroy, Don M., Jakubowska, Anna ORCID: 0000-0002-5650-0501, Lubinski, Jan ORCID: 0000-0003-2931-3003, Sangrajrang, Suleeporn, Brennan, Paul, Olswold, Curtis, Slager, Susan, Shen, Chen-Yang, Hou, Ming-Feng ORCID: 0000-0001-6030-9702, Swerdlow, Anthony ORCID: 0000-0001-5550-4159, Schoemaker, Minouk J., Simard, Jacques, Pharoah, Paul D. P., Kristensen, Vessela, Chenevix-Trench, Georgia ORCID: 0000-0002-1878-2587, Easton, Douglas F., Dunning, Alison M. and Edwards, Stacey L. (2016). Evidence that the 5p12 Variant rs10941679 Confers Susceptibility to Estrogen-Receptor-Positive Breast Cancer through FGF10 and MRPS30 Regulation. Am. J. Hum. Genet., 99 (4). S. 903 - 912. CAMBRIDGE: CELL PRESS. ISSN 1537-6605

Full text not available from this repository.

Abstract

Genome-wide association studies (GWASs) have revealed increased breast cancer risk associated with multiple genetic variants at 5p12. Here, we report the fine mapping of this locus using data from 104,660 subjects from 50 case-control studies in the Breast Cancer Association Consortium (BCAC). With data for 3,365 genotyped and imputed SNPs across a 1 Mb region (positions 44,394,49545,364,167; NCBI build 37), we found evidence for at least three independent signals: the strongest signal, consisting of a single SNP rs10941679, was associated with risk of estrogen-receptor-positive (ER+) breast cancer (per-g allele ER+ = 1.15; 95% CI 1.13-1.18; p = 8.35 x 10(-3)). After adjustment for rs10941679, we detected signal 2, consisting of 38 SNPs more strongly associated with ER-negative (ER-) breast cancer (lead SNP rs6864776: per-a allele OR ER- = 1.10; 95% CI 1.05-1.14; p conditional = 1.44 x 10(-12)), and a single signal 3 SNP (rs200229088: per-t allele OR ER+ = 1.12; 95% CI 1.09-1.15; p conditional = 1.12 x 10(-05)). Expression quantitative trait locus analysis in normal breast tissues and breast tumors showed that the g (risk) allele of rs10941679 was associated with increased expression of FGF10 and MRPS30. Functional assays demonstrated that SNP rs10941679 maps to an enhancer element that physically interacts with the FGF10 and MRPS30 promoter regions in breast cancer cell lines. FGF10 is an oncogene that binds to FGFR2 and is overexpressed in similar to 10% of human breast cancers, whereas MRPS30 plays a key role in apoptosis. These data suggest that the strongest signal of association at 5p12 is mediated through coordinated activation of FGF10 and MRPS30, two candidate genes for breast cancer pathogenesis.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Ghoussaini, MayaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
French, Juliet D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Michailidou, KyriakiUNSPECIFIEDorcid.org/0000-0001-7065-1237UNSPECIFIED
Nord, SiljeUNSPECIFIEDorcid.org/0000-0002-3271-5356UNSPECIFIED
Beesley, JonathanUNSPECIFIEDorcid.org/0000-0003-1942-325XUNSPECIFIED
Canisus, SanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hillman, Kristine M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaufmann, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sivakumaran, HaranUNSPECIFIEDorcid.org/0000-0002-4691-4989UNSPECIFIED
Marjaneh, Mandi MoradiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, Jason S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dennis, JoeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bolla, Manjeet K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, QinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dicks, EdUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Milne, Roger L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hopper, John L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Southey, Melissa C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, Marjanka K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Broeks, AnnegienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muir, KennethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lophatananon, ArtitayaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fasching, Peter A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beckmann, Matthias W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fletcher, OliviaUNSPECIFIEDorcid.org/0000-0001-9387-7116UNSPECIFIED
Johnson, NicholaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sawyer, Elinor J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tomlinson, IanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burwinkel, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marme, FrederikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guenel, PascalUNSPECIFIEDorcid.org/0000-0002-8359-518XUNSPECIFIED
Truong, ThereseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bojesen, Stig E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Flyger, HenrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benitez, JavierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gonzalez-Neira, AnnaUNSPECIFIEDorcid.org/0000-0002-5421-2020UNSPECIFIED
Alonso, RosarioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pita, GuillermoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neuhausen, Susan L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anton-Culver, HodaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brenner, HermannUNSPECIFIEDorcid.org/0000-0002-6129-1572UNSPECIFIED
Arndt, VolkerUNSPECIFIEDorcid.org/0000-0001-9320-8684UNSPECIFIED
Meindl, AlfonsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmutzler, Rita K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brauch, HiltrudUNSPECIFIEDorcid.org/0000-0001-7531-2736UNSPECIFIED
Hamann, UteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tessier, Daniel C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vincent, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nevanlinna, HeliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khan, SofiaUNSPECIFIEDorcid.org/0000-0003-4185-8882UNSPECIFIED
Matsuo, KeitaroUNSPECIFIEDorcid.org/0000-0003-1761-6314UNSPECIFIED
Ito, HidemiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dork, ThiloUNSPECIFIEDorcid.org/0000-0002-9458-0282UNSPECIFIED
Bogdanova, Natalia V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lindblom, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Margolin, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mannermaa, ArtoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kosma, Veli-MattiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wu, Anna H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Van den Berg, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lambrechts, DietherUNSPECIFIEDorcid.org/0000-0002-3429-302XUNSPECIFIED
Floris, GiuseppeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chang-Claude, JennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rudolph, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Radice, PaoloUNSPECIFIEDorcid.org/0000-0001-6298-4111UNSPECIFIED
Barile, MonicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Couch, Fergus J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallberg, EmilyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giles, Graham G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haiman, Christopher A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Le Marchand, LoicUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goldberg, Mark S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teo, Soo H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yip, Cheng HarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borresen-Dale, Anne-LiseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zheng, WeiUNSPECIFIEDorcid.org/0000-0003-1226-070XUNSPECIFIED
Cai, QiuyinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winqvist, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pylkas, KatriUNSPECIFIEDorcid.org/0000-0002-2449-0521UNSPECIFIED
Andrulis, Irene L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Devilee, PeterUNSPECIFIEDorcid.org/0000-0002-8023-2009UNSPECIFIED
Tollenaar, Rob A. E. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Closas, MontserratUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Figueroa, JonineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hall, PerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Czene, KamilaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brand, Judith S.UNSPECIFIEDorcid.org/0000-0002-3720-1274UNSPECIFIED
Darabi, HatefUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eriksson, MikaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hooning, Maartje J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koppert, Linetta B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, JingmeiUNSPECIFIEDorcid.org/0000-0001-8587-7511UNSPECIFIED
Shu, Xiao-OuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zheng, YingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cox, AngelaUNSPECIFIEDorcid.org/0000-0002-5138-1099UNSPECIFIED
Cross, Simon S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shah, MitulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rhenius, ValerieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Choi, Ji-YeobUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kang, DaeheeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartman, MikaelUNSPECIFIEDorcid.org/0000-0001-5726-9965UNSPECIFIED
Chia, Kee SengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kabisch, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Torres, DianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luccarini, CraigUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Conroy, Don M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jakubowska, AnnaUNSPECIFIEDorcid.org/0000-0002-5650-0501UNSPECIFIED
Lubinski, JanUNSPECIFIEDorcid.org/0000-0003-2931-3003UNSPECIFIED
Sangrajrang, SuleepornUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brennan, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olswold, CurtisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Slager, SusanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shen, Chen-YangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hou, Ming-FengUNSPECIFIEDorcid.org/0000-0001-6030-9702UNSPECIFIED
Swerdlow, AnthonyUNSPECIFIEDorcid.org/0000-0001-5550-4159UNSPECIFIED
Schoemaker, Minouk J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simard, JacquesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pharoah, Paul D. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kristensen, VesselaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chenevix-Trench, GeorgiaUNSPECIFIEDorcid.org/0000-0002-1878-2587UNSPECIFIED
Easton, Douglas F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dunning, Alison M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Edwards, Stacey L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-258547
DOI: 10.1016/j.ajhg.2016.07.017
Journal or Publication Title: Am. J. Hum. Genet.
Volume: 99
Number: 4
Page Range: S. 903 - 912
Date: 2016
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1537-6605
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; COMMON VARIANTS; RISK VARIANTS; LOCUS; FOXA1; 2Q35Multiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/25854

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item