Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk.

6533b82efe1ef96bd1293e84

RESEARCH PRODUCT

Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk.

W.y. Lin N.j. Camp M. Ghoussaini J. Beesley K. Michailidou J.l. Hopper C. Apicella M.c. Southey J. Stone M.k. Schmidt A. Broeks L.j. Van't Veer E.j.t. Rutgers K. Muir A. Lophatananon S. Stewart-brown P. Siriwanarangsan P.a. Fasching L. Haeberle A.b. Ekici M.w. Beckmann J. Peto I. Dos-santos-silva O. Fletcher N. Johnson M.k. Bolla Q. Wang J. Dennis E.j. Sawyer T. Cheng I. Tomlinson M.j. Kerin N. Miller F. Marme H.m. Surowy B. Burwinkel P. Guenel T. Truong F. Menegaux C. Mulot S.e. Bojesen B.g. Nordestgaard S.f. Nielsen H. Flyger J. Benitez M.p. Zamora J.i.a. Perez P. Menendez A. Gonzalez-neira G. Pita M.r. Alonso N. Alvarez D. Herrera H. Anton-culver H. Brenner A.k. Dieffenbach V. Arndt C. Stegmaier A. Meindl P. Lichtner R.k. Schmutzler B. Muller-myhsok H. Brauch T. Bruning Y.d. Ko D.c. Tessier D. Vincent F. Bacot H. Nevanlinna K. Aittomaki C. Blomqvist S. Khan K. Matsuo H. Ito H. Iwata A. Horio N.v. Bogdanova N.n. Antonenkova T. Dork A. Lindblom S. Margolin A. Mannermaa V. Kataja V.m. Kosma J.m. Hartikainen A.h. Wu C.c. Tseng D. Van Den Berg D.o. Stram P. Neven E. Wauters H. Wildiers D. Lambrechts J. Chang-claude A. Rudolph P. Seibold D. Flesch-janys P. Radice P. Peterlongo S. Manoukian B. Bonanni F.j. Couch X.s. Wang C. Vachon K. Purrington G.g. Giles R.l. Milne C. Mclean C.a. Haiman B.e. Henderson F. Schumacher L. Le Marchand J. Simard M.s. Goldberg F. Labreche M. Dumont S.h. Teo C.h. Yip N. Hassan E.n. Vithana V. Kristensen W. Zheng S. Deming-halverson M.j. Shrubsole J.r. Long R. Winqvist K. Pylkas A. Jukkola-vuorinen S. Kauppila I.l. Andrulis J.a. Knight G. Glendon S. Tchatchou P. Devilee R.a.e.m. Tollenaar C. Seynaeve C.j. Van Asperen M. Garcia-closas J. Figueroa J. Lissowska L. Brinton K. Czene H. Darabi M. Eriksson J.s. Brand M.j. Hooning A. Hollestelle A.m.w. Van Den Ouweland A. Jager J.m. Li J.j. Liu K. Humphreys X.o. Shu W. Lu Y.t. Gao H. Cai S.s. Cross M.w.r. Reed W. Blot L.b. Signorello Q.y. Cai P.d.p. Pharoah B. Perkins M. Shah F.m. Blows D. Kang K.y. Yoo D.y. Noh M. Hartman H. Miao K.s. Chia T.c. Putti U. Hamann C. Luccarini C. Baynes S. Ahmed M. Maranian C.s. Healey A. Jakubowska J. Lubinski K. Jaworska-bieniek K. Durda S. Sangrajrang V. Gaborieau P. Brennan J. Mckay S. Slager A.e. Toland D. Yannoukakos C.y. Shen C.n. Hsiung P.e. Wu S.l. Ding A. Ashworth M. Jones N. Orr A.j. Swerdlow H. Tsimiklis E. Makalic D.f. Schmidt Q.m. Bui S.j. Chanock D.j. Hunter R. Hein N. Dahmen L. Beckmann K. Aaltonen T.a. Muranen T. Heikkinen A. Irwanto N. Rahman C.a. Turnbull Q. Waisfisz H.e.j. Meijers-heijboer M.a. Adank R.b. Van Der Luijt P. Hall G. Chenevix-trench A. Dunning D.f. Easton A. Cox Genica Network Kconfab Investigators Australian Ovarian Canc Study Grp Breast Ovarian Canc Susceptibility

subject

Genotyping Techniques Research Support U.S. Gov't P.H.S.CASP8 and FADD-Like Apoptosis Regulating Protein Genome-wide association study P.H.S.Medical and Health Sciences Breast and Ovarian Cancer Susceptibility (BOCS) Study Medizinische Fakultät Genetics(clinical)Non-U.S. Gov't Genetics (clinical)Genetics Genetics & Heredity variants Caspase 8 Research Support Non-U.S. Gov't Association Studies Articles General Medicine Biological Sciences ddc:Chromosomes Human Pair 2 kConFab Investigators Female GENICA Network Australian Ovarian Cancer Study Group European Continental Ancestry Group Non-P.H.S.Single-nucleotide polymorphism Breast Neoplasms -Biology Research Support Polymorphism Single Nucleotide White People N.I.H.Breast cancer Research Support N.I.H. Extramural SDG 3 - Good Health and Well-being medicine Genetics Journal Article Humans Genetic Predisposition to Disease ddc:610 gene Genotyping Techniques Genotyping Molecular Biology Genetic association disease Extramural Proteins Odds ratio medicine.disease susceptibility loci Minor allele frequency Case-Control Studies genome-wide association enhancers U.S. Gov't casp8 Research Support U.S. Gov't Non-P.H.S.Genome-Wide Association Study

description

Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regressionmodels adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03-1.07), P = 1 × 10-5. Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P=3 × 10-6), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), P = 1 × 10-9. Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8might be the target gene, suggesting amechanism involving apoptosis.

year	journal	country	edition	language
2014-08-28

10.1093/hmg/ddu431 https://doi.org/10.1093/hmg/ddu431