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

被引：43

作者：

Schumacher, Fredrick R. ^{[2
]}

Cheng, Iona ^{[3
]}

Freedman, Matthew L. ^{[4
]}

Mucci, Lorelei ^{[1
,5
]}

Allen, Naomi E. ^{[10
]}

Pollak, Michael N. ^{[11
]}

Hayes, Richard B. ^{[12
]}

Stram, Daniel O. ^{[2
]}

Canzian, Frederico

Henderson, Brian E. ^{[2
]}

Hunter, David J. ^{[1
,7
]}

Virtamo, Jarmo ^{[14
]}

Manjer, Jonas ^{[15
]}

Gaziano, J. Michael ^{[8
,9
]}

Kolonel, Laurence N. ^{[3
]}

Tjonneland, Anne ^{[16
]}

Albanes, Demetrius ^{[17
]}

Calle, Eugenia E. ^{[18
]}

Giovannucci, Edward ^{[1
,5
,6
]}

Crawford, E. David ^{[19
]}

Haiman, Christopher A. ^{[2
]}

Kraft, Peter ^{[7
]}

Willett, Walter C. ^{[5
]}

Thun, Michael J. ^{[18
]}

Marchand, Loic Le ^{[3
]}

Kaaks, Rudolf ^{[13
]}

Feigelson, Heather Spencer ^{[18
,20
]}

Bueno-de-Mesquita, H. Bas ^{[21
]}

Palli, Domenico ^{[22
]}

Riboli, Elio ^{[23
]}

Lund, Eliv ^{[24
]}

Amiano, Pilar ^{[21
]}

Andriole, Gerald ^{[25
]}

Dunning, Alison M. ^{[26
]}

Trichopoulos, Dimitrios ^{[27
]}

Stampfer, Meir J. ^{[1
,5
]}

Key, Timothy J. ^{[10
]}

Ma, Jing ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA

[2] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[3] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA

[4] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[5] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[6] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[7] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA

[8] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA

[9] VA Boston Healthcare Syst, MAVERIC, Boston, MA 02115 USA

[10] Univ Oxford, Canc Epidemiol Unit, Oxford OX3 7BN, England

[11] McGill Univ, Jewish Gen Hosp, Lady Davis Res Inst, Dept Med & Oncol,Canc Prevent Res Unit, Montreal, PQ H3T 1E2, Canada

[12] NYU, Sch Med, New York, NY 10016 USA

[13] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany

[14] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, FIN-00300 Helsinki, Finland

[15] Malmo Univ Hosp, Dept Surg, S-20502 Malmo, Sweden

[16] Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen, Denmark

[17] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA

[18] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30303 USA

[19] Univ Colorado, Denver Hlth Sci Ctr, Denver, CO 80045 USA

[20] Kaiser Permanente, Denver, CO 80237 USA

[21] Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands

[22] ISPO Canc Res & Prevent Inst, Mol & Nutrit Epidemiol Unit, I-50139 Florence, Italy

[23] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London SW7 2AZ, England

[24] Univ Tromso, Inst Community Med, N-9019 Tromso, Norway

[25] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA

[26] Univ Cambridge, Dept Oncol, Cambridge CB2 1TN, England

[27] Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens 11527, Greece

来源：

HUMAN MOLECULAR GENETICS | 2010年 / 19卷 / 15期

关键词：

GROWTH-FACTOR-I; GENOME-WIDE ASSOCIATION; FACTOR-BINDING PROTEIN-3; BREAST-CANCER; MULTIETHNIC COHORT; CIRCULATING LEVELS; FACTOR (IGF)-I; SERUM-LEVELS; MENDELIAN RANDOMIZATION; MISSING HERITABILITY;

D O I：

10.1093/hmg/ddq210

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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) >= 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.

引用

页码：3089 / 3101

页数：13

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