Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2

التفاصيل البيبلوغرافية
العنوان:	Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2
المؤلفون:	Orr, N., Dudbridge, F., Dryden, N., Maguire, S., Novo, D., Perrakis, E., Johnson, N., Ghoussaini, M., Hopper, J. L., Southey, M. C., Apicella, C., Stone, J., Schmidt, M. K., Broeks, A., Van't Veer, L. J., Hogervorst, F. B., Fasching, P. A., Haeberle, L., Ekici, A. B., Beckmann, M. W., Gibson, L., Aitken, Z., Warren, H., Sawyer, E., Tomlinson, I., Kerin, M. J., Miller, N., Burwinkel, B., Marme, F., Schneeweiss, A., Sohn, C., Guenel, P., Truong, T., Cordina-Duverger, E., Sanchez, M., Bojesen, S. E., Nordestgaard, B. G., Nielsen, S. F., Flyger, H., Benitez, J., Zamora, M. P., Arias Perez, J. I., Menendez, P., Anton-Culver, H., Neuhausen, S. L., Brenner, H., Dieffenbach, A. K., Arndt, V., Stegmaier, C., Hamann, U., Brauch, H., Justenhoven, C., Bruning, T., Ko, Y.-D., Nevanlinna, H., Aittomaki, K., Blomqvist, C., Khan, S., Bogdanova, N., Dork, T., Lindblom, A., Margolin, S., Mannermaa, A., Kataja, V., Kosma, V.-M., Hartikainen, J. M., Chenevix-Trench, G., Beesley, J., Lambrechts, D., Moisse, M., Floris, G., Beuselinck, B., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Radice, P., Peterlongo, P., Peissel, B., Pensotti, V., Couch, F. J., Olson, J. E., Slettedahl, S., Vachon, C., Giles, G. G., Milne, R. L., McLean, C., Haiman, C. A., Henderson, B. E., Schumacher, F., Le Marchand, L., Simard, J., Goldberg, M. S., Labreche, F., Dumont, M., Kristensen, V., Alnaes, G. G., Nord, S., Borresen-Dale, A.-L., Zheng, W., Deming-Halverson, S., Shrubsole, M., Long, J., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Andrulis, I. L., Knight, J. A., Glendon, G., Tchatchou, S., Devilee, P., Tollenaar, R. A. E. M., Seynaeve, C. M., Van Asperen, C. J., Garcia-Closas, M., Figueroa, J., Chanock, S. J., Lissowska, J., Czene, K., Darabi, H., Eriksson, M., Klevebring, D., Hooning, M. J., Hollestelle, A., van Deurzen, C. H. M., Kriege, M., Hall, P., Li, J., Liu, J., Humphreys, K., Cox, A., Cross, S. S., Reed, M. W. R., Pharoah, P. D. P., Dunning, A. M., Shah, M., Perkins, B. J., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Ashworth, A., Swerdlow, A., Jones, M., Schoemaker, M. J., Meindl, A., Schmutzler, R. K., Olswold, C., Slager, S., Toland, A. E., Yannoukakos, D., Muir, K., Lophatananon, A., Stewart-Brown, S., Siriwanarangsan, P., Matsuo, K., Ito, H., Iwata, H., Ishiguro, J., Wu, A. H., Tseng, C.-c., Van Den Berg, D., Stram, D. O., Teo, S. H., Yip, C. H., Kang, P., Ikram, M. K., Shu, X.-O., Lu, W., Gao, Y.-T., Cai, H., Kang, D., Choi, J.-Y., Park, S. K., Noh, D.-Y., Hartman, M., Miao, H., Lim, W. Y., Lee, S. C., Sangrajrang, S., Gaborieau, V., Brennan, P., Mckay, J., Wu, P.-E., Hou, M.-F., Yu, J.-C., Shen, C.-Y., Blot, W., Cai, Q., Signorello, L. B., Luccarini, C., Bayes, C., Ahmed, S., Maranian, M., Healey, C. S., Gonzalez-Neira, A., Pita, G., Alonso, M. R., Alvarez, N., Herrero, D., Tessier, D. C., Vincent, D., Bacot, F., Hunter, D. J., Lindstrom, S., Dennis, J., Michailidou, K., Bolla, M. K., Easton, D. F., dos Santos Silva, I., Fletcher, O., Peto, J.
بيانات النشر:	Oxford University Press (OUP)
سنة النشر:	2015
المجموعة:	National University of Ireland (NUI), Galway: ARAN
مصطلحات موضوعية:	genome-wide association, estrogen-receptor-alpha, confer susceptibility, functional variants, common variants, analyses reveal, risk locus, expression, binding, foxa1
الوصف:	We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88-0.92]; P-value = 1.58 x 10(-25)). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans 14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08-1.17]; P-value = 7.89 x 10(-09)) and rs13294895 (OR = 1.09 [1.06-1.12]; P-value = 2.97 x 10(-11)). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06-1.18]; P-value = 2.77 x 10(-05)). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-alpha, FOXA1 and GATA-3. In vitro analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the KLF4 gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis.
نوع الوثيقة:	article in journal/newspaper
اللغة:	unknown
العلاقة:	Human Molecular Genetics; Orr, N. Dudbridge, F.; Dryden, N.; Maguire, S.; Novo, D.; Perrakis, E.; Johnson, N.; Ghoussaini, M.; Hopper, J. L.; Southey, M. C.; Apicella, C.; Stone, J.; Schmidt, M. K.; Broeks, A.; Van't Veer, L. J.; Hogervorst, F. B.; Fasching, P. A.; Haeberle, L.; Ekici, A. B.; Beckmann, M. W.; Gibson, L.; Aitken, Z.; Warren, H.; Sawyer, E.; Tomlinson, I.; Kerin, M. J.; Miller, N.; Burwinkel, B.; Marme, F.; Schneeweiss, A.; Sohn, C.; Guenel, P.; Truong, T.; Cordina-Duverger, E.; Sanchez, M.; Bojesen, S. E.; Nordestgaard, B. G.; Nielsen, S. F.; Flyger, H.; Benitez, J.; Zamora, M. P.; Arias Perez, J. I.; Menendez, P.; Anton-Culver, H.; Neuhausen, S. L.; Brenner, H.; Dieffenbach, A. K.; Arndt, V.; Stegmaier, C.; Hamann, U.; Brauch, H.; Justenhoven, C.; Bruning, T.; Ko, Y.-D.; Nevanlinna, H.; Aittomaki, K.; Blomqvist, C.; Khan, S.; Bogdanova, N.; Dork, T.; Lindblom, A.; Margolin, S.; Mannermaa, A.; Kataja, V.; Kosma, V.-M.; Hartikainen, J. M.; Chenevix-Trench, G.; Beesley, J.; Lambrechts, D.; Moisse, M.; Floris, G.; Beuselinck, B.; Chang-Claude, J.; Rudolph, A.; Seibold, P.; Flesch-Janys, D.; Radice, P.; Peterlongo, P.; Peissel, B.; Pensotti, V.; Couch, F. J.; Olson, J. E.; Slettedahl, S.; Vachon, C.; Giles, G. G.; Milne, R. L.; McLean, C.; Haiman, C. A.; Henderson, B. E.; Schumacher, F.; Le Marchand, L.; Simard, J.; Goldberg, M. S.; Labreche, F.; Dumont, M.; Kristensen, V.; Alnaes, G. G.; Nord, S.; Borresen-Dale, A.-L.; Zheng, W.; Deming-Halverson, S.; Shrubsole, M.; Long, J.; Winqvist, R.; Pylkas, K.; Jukkola-Vuorinen, A.; Grip, M.; Andrulis, I. L.; Knight, J. A.; Glendon, G.; Tchatchou, S.; Devilee, P.; Tollenaar, R. A. E. M.; Seynaeve, C. M.; Van Asperen, C. J.; Garcia-Closas, M.; Figueroa, J.; Chanock, S. J.; Lissowska, J.; Czene, K.; Darabi, H.; Eriksson, M.; Klevebring, D.; Hooning, M. J.; Hollestelle, A.; van Deurzen, C. H. M.; Kriege, M.; Hall, P.; Li, J.; Liu, J.; Humphreys, K.; Cox, A.; Cross, S. S.; Reed, M. W. R.; Pharoah, P. D. P.; Dunning, A. M.; Shah, M.; Perkins, B. J.; Jakubowska, A.; Lubinski, J.; Jaworska-Bieniek, K.; Durda, K.; Ashworth, A.; Swerdlow, A.; Jones, M.; Schoemaker, M. J.; Meindl, A.; Schmutzler, R. K.; Olswold, C.; Slager, S.; Toland, A. E.; Yannoukakos, D.; Muir, K.; Lophatananon, A.; Stewart-Brown, S.; Siriwanarangsan, P.; Matsuo, K.; Ito, H.; Iwata, H.; Ishiguro, J.; Wu, A. H.; Tseng, C.-c.; Van Den Berg, D.; Stram, D. O.; Teo, S. H.; Yip, C. H.; Kang, P.; Ikram, M. K.; Shu, X.-O.; Lu, W.; Gao, Y.-T.; Cai, H.; Kang, D.; Choi, J.-Y.; Park, S. K.; Noh, D.-Y.; Hartman, M.; Miao, H.; Lim, W. Y.; Lee, S. C.; Sangrajrang, S.; Gaborieau, V.; Brennan, P.; Mckay, J.; Wu, P.-E.; Hou, M.-F.; Yu, J.-C.; Shen, C.-Y.; Blot, W.; Cai, Q.; Signorello, L. B.; Luccarini, C.; Bayes, C.; Ahmed, S.; Maranian, M.; Healey, C. S.; Gonzalez-Neira, A.; Pita, G.; Alonso, M. R.; Alvarez, N.; Herrero, D.; Tessier, D. C.; Vincent, D.; Bacot, F.; Hunter, D. J.; Lindstrom, S.; Dennis, J.; Michailidou, K.; Bolla, M. K.; Easton, D. F.; dos Santos Silva, I.; Fletcher, O.; Peto, J.;; , (2015). Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2. Human Molecular Genetics 24 (10), 2966-2984; 0964-6906,1460-2083; http://hdl.handle.net/10379/13361Test
DOI:	10.1093/hmg/ddv035
الإتاحة:	https://doi.org/10.1093/hmg/ddv035Test http://hdl.handle.net/10379/13361Test
حقوق:	Attribution-NonCommercial-NoDerivs 3.0 Ireland ; https://creativecommons.org/licenses/by-nc-nd/3.0/ieTest/
رقم الانضمام:	edsbas.49DF5617
قاعدة البيانات:	BASE

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الوصف
DOI:	10.1093/hmg/ddv035