TY - JOUR
T1 - HapMap-based study of the 17q21 ERBB2 amplicon in susceptibility to breast cancer
AU - Benusiglio, P. R.
AU - Pharoah, P. D.
AU - Smith, P. L.
AU - Lesueur, F.
AU - Conroy, D.
AU - Luben, R. N.
AU - Dew, G.
AU - Jordan, C.
AU - Dunning, A.
AU - Easton, D. F.
AU - Ponder, B. A.J.
N1 - Funding Information:
PRB is supported by the Ligue Genevoise contre le Cancer, Switzerland (N/Ref 0208). BAJP is a Gibb Fellow, DFE is a Principal Fellow and PDP is a Senior Clinical Research Fellow of Cancer Research United Kingdom. This work was funded by Cancer Research United Kingdom. We are grateful to Craig Luccarini for his laboratory expertise and to Shahana Ahmed and Oluseun Ajai for their technical help.
PY - 2006/12/18
Y1 - 2006/12/18
N2 - 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 ≥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.
AB - 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 ≥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.
KW - Amplicon
KW - Breast neoplasms
KW - ERBB2
KW - Genetic susceptibility
KW - HapMap
KW - Single-nucleotide polymorphism
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U2 - 10.1038/sj.bjc.6603473
DO - 10.1038/sj.bjc.6603473
M3 - Article
C2 - 17117180
AN - SCOPUS:33845630768
SN - 0007-0920
VL - 95
SP - 1689
EP - 1695
JO - British journal of cancer
JF - British journal of cancer
IS - 12
ER -