title: HapMap-based study of the 17q21 ERBB2 amplicon in susceptibility to breast cancer.
abstract: ERBB2 is frequently amplified in breast tumours as part of a wide region of amplification on chromosome 17q21. This amplicon contains many candidate genes for breast cancer susceptibility. We used a genetic association study design to determine if common genetic variation (frequency>or=5%) in a 400-kb region surrounding ERBB2 and containing the PPARBP, CRK7, NEUROD2, PPP1R1B, STARD3, TCAP, PNMT, CAB2, ERBB2, C17ORF37, GRB7 and ZNFN1A3 genes, was associated with breast cancer risk. Sixteen tagging single-nucleotide polymorphisms (tSNPs) selected within blocks of linkage disequilibrium from the HapMap database, one HapMap singleton SNP, and six additional SNPs randomly selected from dbSNP were genotyped using Taqman in a large study set of British women (2275 cases, 2280 controls). We observed no association between any of the genotypes or associated haplotypes and disease risk. In order to simulate unidentified SNPs, we performed the leave-one-out cross-validation procedure on the HapMap data; over 90% of the common genetic variation was well represented by tagging polymorphisms. We are therefore likely to have tagged any common variants present in our population. In summary, we found no association between common genetic variation in the 17q21 ERBB2 amplicon and breast cancer risk in British women.
authors.affiliation: Strangeways Research Laboratory, Cancer Research UK Department of Oncology, University of Cambridge, UK, and Department of Internal Medecine, Hôpital Cantonal Universitaire de Genève, Switzerland. pbenusiglio@yahoo.com
authors.forename: P R
authors.initials: PR
authors.lastname: Benusiglio
authors.forename: P D
authors.initials: PD
authors.lastname: Pharoah
authors.forename: P L
authors.initials: PL
authors.lastname: Smith
authors.forename: F
authors.initials: F
authors.lastname: Lesueur
authors.forename: D
authors.initials: D
authors.lastname: Conroy
authors.forename: R N
authors.initials: RN
authors.lastname: Luben
authors.forename: G
authors.initials: G
authors.lastname: Dew
authors.forename: C
authors.initials: C
authors.lastname: Jordan
authors.forename: A
authors.initials: A
authors.lastname: Dunning
authors.forename: D F
authors.initials: DF
authors.lastname: Easton
authors.forename: B A J
authors.initials: BA
authors.lastname: Ponder
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases