학술논문
Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I and its binding protein, and risk of prostate and breast cancer
Document Type
Author
Gu, Fangyi; Schumacher, Fredrick R; Canzian, Federico; Allen, Naomi E; Albanes, Demetrius; Berg, Christine D; Berndt, Sonja I; Boeing, Heiner; Bueno-de-Mesquita, H Bas; Buring, Julie E; Chabbert-Buffet, Nathalie; Chanock, Stephen J; Clavel-Chapelon, Françoise; Dumeaux, Vanessa; Gaziano, J Michael; Giovannucci, Edward L; Haiman, Christopher A; Hankinson, Susan E; Hayes, Richard B; Henderson, Brian E; Hunter, David J; Hoover, Robert N; Johansson, Mattias; Key, Timothy J; Khaw, Kay-Tee; Kolonel, Laurence N; Lagiou, Pagona; Lee, I-Min; LeMarchand, Loic; Lund, Eiliv; Ma, Jing; Onland-Moret, N Charlotte; Overvad, Kim; Rodriguez, Laudina; Sacerdote, Carlotta; Sánchez, Maria-José; Stampfer, Meir J; Stattin, Pär; Stram, Daniel O; Thomas, Gilles; Thun, Michael J; Tjønneland, Anne; Trichopoulos, Dimitrios; Tumino, Rosario; Virtamo, Jarmo; Weinstein, Stephanie J; Willett, Walter C; Yeager, Meredith; Zhang, Shumin M; Kaaks, Rudolf; Riboli, Elio; Ziegler, Regina G; Kraft, Peter
Source
Cancer Epidemiology, Biomarkers and Prevention. 19(11):2877-2887
Subject
Language
English
ISSN
1055-9965
1538-7755
1538-7755
Abstract
Background: Circulating levels of insulin-like growth factor I (IGF-I) and its main binding protein, IGF binding protein 3 (IGFBP-3), have been associated with risk of several types of cancer. Heritable factors explain up to 60% of the variation in IGF-I and IGFBP-3 in studies of adult twins.Methods: We systematically examined common genetic variation in 18 genes in the IGF signaling pathway for associations with circulating levels of IGF-I and IGFBP-3. A total of 302 single nucleotide polymorphisms (SNP) were genotyped in >5,500 Caucasian men and 5,500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium.Results: After adjusting for multiple testing, SNPs in the IGF1 and SSTR5 genes were significantly associated with circulating IGF-I (P < 2.1 × 10−4); SNPs in the IGFBP3 and IGFALS genes were significantly associated with circulating IGFBP-3. Multi-SNP models explained R2 = 0.62% of the variation in circulating IGF-I and 3.9% of the variation in circulating IGFBP-3. We saw no significant association between these multi-SNP predictors of circulating IGF-I or IGFBP-3 and risk of prostate or breast cancers.Conclusion: Common genetic variation in the IGF1 and SSTR5 genes seems to influence circulating IGF-I levels, and variation in IGFBP3 and IGFALS seems to influence circulating IGFBP-3. However, these variants explain only a small percentage of the variation in circulating IGF-I and IGFBP-3 in Caucasian men and women.Impact: Further studies are needed to explore contributions from other genetic factors such as rare variants in these genes and variation outside of these genes.