TY - JOUR
T1 - IGF-1, IGFBP-1 and IGFBP-3 polymorphisms predict circulating IGF levels but not breast cancer risk
T2 - Findings from the breast and prostate cancer cohort consortium (BPC3)
AU - Patel, Alpa V.
AU - Cheng, Iona
AU - Canzian, Ferderico
AU - Le Marchand, Loïc
AU - Thun, Michael J.
AU - Berg, Christine D.
AU - Buring, Julie
AU - Calle, Eugenia E.
AU - Chanock, Stephan
AU - Clavel-Chapelon, Francoise
AU - Cox, David G.
AU - Dorronsoro, Miren
AU - Dossus, Laure
AU - Halman, Christopher A.
AU - Hankinson, Susan E.
AU - Henderson, Brian E.
AU - Hoover, Robert
AU - Hunter, David J.
AU - Kaaks, Rudolf
AU - Kolonel, Laurence N.
AU - Kraft, Peter
AU - Linseisen, Jakob
AU - Lund, Elliv
AU - Manjer, Jonas
AU - McCarty, Catherine
AU - Peeters, Petra H.M.
AU - Pike, Malcolm C.
AU - Pollak, Michael
AU - Riboli, Elio
AU - Stram, Daniel O.
AU - Tjonneland, Anne
AU - Travis, Ruth C.
AU - Trichopoulos, Dimitrios
AU - Tumino, Rosario
AU - Yeager, Meredith
AU - Ziegler, Regina G.
AU - Spencer-Feigelson, Heather
PY - 2008/7/2
Y1 - 2008/7/2
N2 - IGF-1 has been shown to promote proliferation of normal epithelial breast cells, and the IGF pathway has also been linked to mammary carcinogenesis in animal models. We comprehensively examined the association between common genetic variation in the IGF1, IGFBP1, and IGFBP3 genes in relation to circulating IGF-1 and IGFBP-3 levels and breast cancer risk within the NCI Breast, and Prostate Cancer Cohort, Consortium (BPC3). This analysis included 6,912 breast cancer cases and 8,891 matched controls (n = 6,410 for circulating IGF-1 and 6,275 for circulating IGFBP-3 analyses) comprised primarily of Caucasian women drawn from six large cohorts. Linkage disequilibrium and haplotype patterns were characterized in the regions surrounding IGF1 and the qenes coding for two of its binding proteins, IGFBP1 and IGFBP3. In total, thirty haplotype-tagging single nucleotide polymorphisms (htSNP) were selected to provide high coverage of common ha of common haplotype; the haplotype structure was defined across fourh haplotype blocks for IGF1 and three for IGFBP1 and IGFBP3. Specific IGF1 SNPs individually accounted for up to 5% change in circulating IGF-1 levels and individual IGFBP3 SNPs were associated up to 12% change in circulating IGFBP-3 levels, but no associations were observed between these polymorphisms and breast cancer risk. Logistic regression analyses found no associations between breast cancer and any htSNPs or haplotypes in IGF1, IGFBP1, or IGFBP3. No effect modification was observed in analyses stratified by menopausal status, family history of breast cancer, body mass index, or postmenopausal hormone therapy, or for analyses stratified by stage at diagnosis or hormone receptor status. In summary, the impact of genetic variation in IGF1 and IGFBP3 on circulating IGF level does not appear to substantially influence breast cancer risk substantially among primarily Caucasian postmenopausal women.
AB - IGF-1 has been shown to promote proliferation of normal epithelial breast cells, and the IGF pathway has also been linked to mammary carcinogenesis in animal models. We comprehensively examined the association between common genetic variation in the IGF1, IGFBP1, and IGFBP3 genes in relation to circulating IGF-1 and IGFBP-3 levels and breast cancer risk within the NCI Breast, and Prostate Cancer Cohort, Consortium (BPC3). This analysis included 6,912 breast cancer cases and 8,891 matched controls (n = 6,410 for circulating IGF-1 and 6,275 for circulating IGFBP-3 analyses) comprised primarily of Caucasian women drawn from six large cohorts. Linkage disequilibrium and haplotype patterns were characterized in the regions surrounding IGF1 and the qenes coding for two of its binding proteins, IGFBP1 and IGFBP3. In total, thirty haplotype-tagging single nucleotide polymorphisms (htSNP) were selected to provide high coverage of common ha of common haplotype; the haplotype structure was defined across fourh haplotype blocks for IGF1 and three for IGFBP1 and IGFBP3. Specific IGF1 SNPs individually accounted for up to 5% change in circulating IGF-1 levels and individual IGFBP3 SNPs were associated up to 12% change in circulating IGFBP-3 levels, but no associations were observed between these polymorphisms and breast cancer risk. Logistic regression analyses found no associations between breast cancer and any htSNPs or haplotypes in IGF1, IGFBP1, or IGFBP3. No effect modification was observed in analyses stratified by menopausal status, family history of breast cancer, body mass index, or postmenopausal hormone therapy, or for analyses stratified by stage at diagnosis or hormone receptor status. In summary, the impact of genetic variation in IGF1 and IGFBP3 on circulating IGF level does not appear to substantially influence breast cancer risk substantially among primarily Caucasian postmenopausal women.
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U2 - 10.1371/journal.pone.0002578
DO - 10.1371/journal.pone.0002578
M3 - Article
C2 - 18596909
AN - SCOPUS:49749123796
VL - 3
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 7
M1 - e2578
ER -