A comprehensive analysis of common IGF1, IGFBP1 and IGFBP3 genetic variation with prospective IGF-I and IGFBP-3 blood levels and prostate cancer risk among Caucasians.

Schumacher, F; Cheng, I; Freedman, M; Mucci, L; Allen, N; Pollak, M; Hayes, R; Stram, DO; Canzian, F; Henderson, B; Hunter, D; Virtamo, J; Manjer, J; Gaziano, J; Kolonel, L; Tjønneland, A; Albanes, D; Calle, E; Giovannucci, E; Crawford, E; Haiman, C; Kraft, P; Willett, W; Thun, M; Le Marchand, L

Women's Health Collection

Journal article

A comprehensive analysis of common IGF1, IGFBP1 and IGFBP3 genetic variation with prospective IGF-I and IGFBP-3 blood levels and prostate cancer risk among Caucasians.

Abstract:: The insulin-like growth factor (IGF) pathway has been implicated in prostate development and carcinogenesis. We conducted a comprehensive analysis, utilizing a resequencing and tagging single-nucleotide polymorphism (SNP) approach, between common genetic variation in the IGF1, IGF binding protein (BP) 1, and IGFBP3 genes with IGF-I and IGFBP-3 blood levels, and prostate cancer (PCa) risk, among Caucasians in the NCI Breast and Prostate Cancer Cohort Consortium. We genotyped 14 IGF1 SNPs and 16 IGFBP1/IGFBP3 SNPs to capture common [minor allele frequency (MAF) >or= 5%] variation among Caucasians. For each SNP, we assessed the geometric mean difference in IGF blood levels (N = 5684) across genotypes and the association with PCa risk (6012 PCa cases/6641 controls). We present two-sided statistical tests and correct for multiple comparisons. A non-synonymous IGFBP3 SNP in exon 1, rs2854746 (Gly32Ala), was associated with IGFBP-3 blood levels (P(adj) = 8.8 x 10(-43)) after adjusting for the previously established IGFBP3 promoter polymorphism A-202C (rs2854744); IGFBP-3 blood levels were 6.3% higher for each minor allele. For IGF1 SNP rs4764695, the risk estimates among heterozygotes was 1.01 (99% CI: 0.90-1.14) and 1.20 (99% CI: 1.06-1.37) for variant homozygotes with overall PCa risk. The corrected allelic P-value was 8.7 x 10(-3). IGF-I levels were significantly associated with PCa risk (P(trend) = 0.02) with a 21% increase of PCa risk when compared with the highest quartile to the lowest quartile. We have identified SNPs significantly associated with IGFBP-3 blood levels, but none of these alter PCa risk; however, a novel IGF1 SNP, not associated with IGF-I blood levels, shows preliminary evidence for association with PCa risk among Caucasians.

Publication status:: Published

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APA Style

Schumacher, F., Cheng, I., Freedman, M., Mucci, L., Allen, N., Pollak, M., Hayes, R., Stram, D. O., Canzian, F., Henderson, B., Hunter, D., Virtamo, J., Manjer, J., Gaziano, J., Kolonel, L., Tjønneland, A., Albanes, D., Calle, E., Giovannucci, E., … Le Marchand, L. (2010). A comprehensive analysis of common IGF1, IGFBP1 and IGFBP3 genetic variation with prospective IGF-I and IGFBP-3 blood levels and prostate cancer risk among Caucasians. Human Molecular Genetics, 19(15), 3089–3101.

MLA Style

Schumacher, F, et al. “A Comprehensive Analysis of Common IGF1, IGFBP1 and IGFBP3 Genetic Variation with Prospective IGF-I and IGFBP-3 Blood Levels and Prostate Cancer Risk among Caucasians.” Human Molecular Genetics, vol. 19, no. 15, 2010, pp. 3089–101.

Chicago Style

Schumacher, F, I Cheng, M Freedman, et al. 2010. “A Comprehensive Analysis of Common IGF1, IGFBP1 and IGFBP3 Genetic Variation with Prospective IGF-I and IGFBP-3 Blood Levels and Prostate Cancer Risk among Caucasians.” Human Molecular Genetics 19 (15): 3089–3101.
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