Ghoussaini M, Edwards SL, Michailidou K, Nord S, Lari RCS, Desai K, Kar S, Hillman KM, Kaufmann S, Glubb DM, Beesley J, Dennis J, Bolla MK, Wang Q, Dicks E, Guo Q, Schmidt MK, Shah M, Luben R, Brown J, Czene K, Darabi H, Eriksson M, Klevebring D, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Lambrechts D, Thienpont B, Neven P, Wildiers H, Broeks A, Van'T Veer LJ, Rutgers EJT, Couch FJ, Olson JE, Hallberg E, Vachon C, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Peto J, Dos-Santos-Silva I, Gibson L, Nevanlinna H, Muranen TA, Aittomaki K, Blomqvist C, Hall P, Li J, Liu J, Humphreys K, Kang D, Choi JY, Park SK, Noh DY, Matsuo K, Ito H, Iwata H, Yatabe Y, Guenel P, Truong T, Menegaux F, Sanchez M, Burwinkel B, Marme F, Schneeweiss A, Sohn C, Wu AH, Tseng CC, Van Den Berg D, Stram DO, Benitez J, Pilar Zamora M, Arias Perez JI, Menendez P, Shu XO, Lu W, Gao YT, Cai Q, Cox A, Cross SS, Reed MWR, Andrulis IL, Knight JA, Glendon G, Tchatchou S, Sawyer EJ, Tomlinson I, Kerin MJ, Miller N, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Lindblom A, Margolin S, Teo SH, Yip CH, Lee DSC, Wong TY, Hooning MJ, Martens JWM, Collee JM, Van Deurzen CHM, Hopper JL, Southey MC, Tsimiklis H, Kapuscinski MK, Shen CY, Wu PE, Yu JC, Chen ST, Alnaes GG, Borresen-Dale AL, Giles GG, Milne RL, Mclean C, Muir K, Lophatananon A, Stewart-Brown S, Siriwanarangsan P, Hartman M, Miao H, Buhari SABS, Teo YY, Fasching P, Häberle L, Ekici AB, Beckmann M, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Swerdlow A, Ashworth A, Orr N, Schoemaker MJ, Garcia-Closas M, Figueroa J, Chanock SJ, Lissowska J, Simard J, Goldberg MS, Labreche F, Dumont M, Winqvist R, Pylkas K, Jukkola-Vuorinen A, Brauch H, Bruening T, Koto YD, Radice P, Peterlongo P, Bonanni B, Volorio S, Doerk T, Bogdanova NV, Helbig S, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Devilee P, Tollenaar RAEM, Seynaeve C, Van Asperen CJ, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Slager S, Toland AE, Ambrosone CB, Yannoukakos D, Sangrajrang S, Gaborieau V, Brennan P, Mckay J, Hamann U, Torres D, Zheng W, Long J, Anton-Culver H, Neuhausen SL, Luccarini C, Baynes C, Ahmed S, Maranian M, Healey CS, Gonzalez-Neira A, Pita G, Alonso MR, Alvarez N, Herrero D, Tessier DC, Vincent D, Bacot F, De Santiago I, Carroll J, Caldas C, Brown MA, Lupien M, Kristensen VN, Pharoah PDP, Chenevix-Trench G, French JD, Easton DF, Dunning AM (2014)
Publication Type: Journal article
Publication year: 2014
Book Volume: 4
Pages Range: 4999
DOI: 10.1038/ncomms5999
GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology.
APA:
Ghoussaini, M., Edwards, S.L., Michailidou, K., Nord, S., Lari, R.C.-S., Desai, K.,... Dunning, A.M. (2014). Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation. Nature Communications, 4, 4999. https://doi.org/10.1038/ncomms5999
MLA:
Ghoussaini, Maya, et al. "Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation." Nature Communications 4 (2014): 4999.
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