Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I and its binding protein, and risk of prostate and breast cancer.

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 R(2) = 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.

• Authors: Fangyi Gu, Fredrick R Schumacher, Federico Canzian, Naomi E Allen, Demetrius Albanes, Christine D Berg, Sonja I Berndt, Heiner Boeing, H Bas Bueno-de-Mesquita, Julie E Buring, Nathalie Chabbert-Buffet, Stephen J Chanock, Françoise Clavel-Chapelon, Vanessa Dumeaux, J Michael Gaziano, Edward L Giovannucci, Christopher A Haiman, Susan E Hankinson, Richard B Hayes, Brian E Henderson, David J Hunter, Robert N Hoover, Mattias Johansson, Timothy J Key, Kay-Tee Khaw, Laurence N Kolonel, Pagona Lagiou, I-Min Lee, Loic LeMarchand, Eiliv Lund, Jing Ma, N Charlotte Onland-Moret, Kim Overvad, Laudina Rodriguez, Carlotta Sacerdote, Maria-José Sánchez, Meir J Stampfer, Pär Stattin, Daniel O Stram, Gilles Thomas, Michael J Thun, Anne Tjønneland, Dimitrios Trichopoulos, Rosario Tumino, Jarmo Virtamo, Stephanie J Weinstein, Walter C Willett, Meredith Yeager, Shumin M Zhang, Rudolf Kaaks, Elio Riboli, Regina G Ziegler, Peter Kraft
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 19 Issue 11 Pg. 2877-87 (Nov 2010) ISSN: 1538-7755 [Electronic] United States
• PMID: 20810604 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
• Copyright: ©2010 AACR.

Chemical References

• Biomarkers, Tumor
• Carrier Proteins
• Glycoproteins
• IGFBP3 protein, human
• Insulin-Like Growth Factor Binding Protein 3
• Insulin-Like Growth Factor Binding Proteins
• Receptors, Somatostatin
• insulin-like growth factor binding protein, acid labile subunit
• Insulin-Like Growth Factor I
• somatostatin receptor 5

Topics

• Aged
• Biomarkers, Tumor (blood, genetics)
• Breast Neoplasms (blood, genetics)
• Carrier Proteins (genetics)
• Cohort Studies
• Enzyme-Linked Immunosorbent Assay
• Female
• Genetic Predisposition to Disease (genetics)
• Genotype
• Glycoproteins (genetics)
• Humans
• Insulin-Like Growth Factor Binding Protein 3
• Insulin-Like Growth Factor Binding Proteins (blood, genetics)
• Insulin-Like Growth Factor I (genetics, metabolism)
• Male
• Middle Aged
• Polymerase Chain Reaction
• Polymorphism, Single Nucleotide
• Prostatic Neoplasms (blood, genetics)
• Receptors, Somatostatin (genetics)
• Risk Factors
• Signal Transduction (genetics)