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

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. HendersonDavid 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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2877-2887
Number of pages11
JournalCancer Epidemiology Biomarkers and Prevention
Volume19
Issue number11
DOIs
StatePublished - Nov 2010
Externally publishedYes

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Insulin-Like Growth Factor Binding Protein 3
Somatomedins
Insulin-Like Growth Factor I
Prostatic Neoplasms
Carrier Proteins
Breast Neoplasms
Genes
Single Nucleotide Polymorphism
Twin Studies

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

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

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 19, No. 11, 11.2010, p. 2877-2887.

Research output: Contribution to journalArticle

Gu, F, Schumacher, FR, Canzian, F, Allen, NE, Albanes, D, Berg, CD, Berndt, SI, Boeing, H, Bueno-de-Mesquita, HB, Buring, JE, Chabbert-Buffet, N, Chanock, SJ, Clavel-Chapelon, F, Dumeaux, V, Gaziano, JM, Giovannucci, EL, Haiman, CA, Hankinson, SE, Hayes, RB, Henderson, BE, Hunter, DJ, Hoover, RN, Johansson, M, Key, TJ, Khaw, KT, Kolonel, LN, Lagiou, P, Lee, IM, LeMarchand, L, Lund, E, Ma, J, Onland-Moret, NC, Overvad, K, Rodriguez, L, Sacerdote, C, Sánchez, MJ, Stampfer, MJ, Stattin, P, Stram, DO, Thomas, G, Thun, MJ, Tjønneland, A, Trichopoulos, D, Tumino, R, Virtamo, J, Weinstein, SJ, Willett, WC, Yeager, M, Zhang, SM, Kaaks, R, Riboli, E, Ziegler, RG & Kraft, P 2010, 'Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I and its binding protein, and risk of prostate and breast cancer', Cancer Epidemiology Biomarkers and Prevention, vol. 19, no. 11, pp. 2877-2887. https://doi.org/10.1158/1055-9965.EPI-10-0507
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. / Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I and its binding protein, and risk of prostate and breast cancer. In: Cancer Epidemiology Biomarkers and Prevention. 2010 ; Vol. 19, No. 11. pp. 2877-2887.
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title = "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 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.",
author = "Fangyi Gu and Schumacher, {Fredrick R.} and Federico Canzian and Allen, {Naomi E.} and Demetrius Albanes and Berg, {Christine D.} and Berndt, {Sonja I.} and Heiner Boeing and Bueno-de-Mesquita, {H. Bas} and Buring, {Julie E.} and Nathalie Chabbert-Buffet and Chanock, {Stephen J.} and Fran{\cc}oise Clavel-Chapelon and Vanessa Dumeaux and Gaziano, {J. Michael} and Giovannucci, {Edward L.} and Haiman, {Christopher A.} and Hankinson, {Susan E.} and Hayes, {Richard B.} and Henderson, {Brian E.} and Hunter, {David J.} and Hoover, {Robert N.} and Mattias Johansson and Key, {Timothy J.} and Khaw, {Kay Tee} and Kolonel, {Laurence N.} and Pagona Lagiou and Lee, {I. Min} and Loic LeMarchand and Eiliv Lund and Jing Ma and Onland-Moret, {N. Charlotte} and Kim Overvad and Laudina Rodriguez and Carlotta Sacerdote and S{\'a}nchez, {Maria Jos{\'e}} and Stampfer, {Meir J.} and P{\"a}r Stattin and Stram, {Daniel O.} and Gilles Thomas and Thun, {Michael J.} and Anne Tj{\o}nneland and Dimitrios Trichopoulos and Rosario Tumino and Jarmo Virtamo and Weinstein, {Stephanie J.} and Willett, {Walter C.} and Meredith Yeager and Zhang, {Shumin M.} and Rudolf Kaaks and Elio Riboli and Ziegler, {Regina G.} and Peter Kraft",
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journal = "Cancer Epidemiology Biomarkers and Prevention",
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TY - JOUR

T1 - Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I and its binding protein, and risk of prostate and breast cancer

AU - Gu, Fangyi

AU - Schumacher, Fredrick R.

AU - Canzian, Federico

AU - Allen, Naomi E.

AU - Albanes, Demetrius

AU - Berg, Christine D.

AU - Berndt, Sonja I.

AU - Boeing, Heiner

AU - Bueno-de-Mesquita, H. Bas

AU - Buring, Julie E.

AU - Chabbert-Buffet, Nathalie

AU - Chanock, Stephen J.

AU - Clavel-Chapelon, Françoise

AU - Dumeaux, Vanessa

AU - Gaziano, J. Michael

AU - Giovannucci, Edward L.

AU - Haiman, Christopher A.

AU - Hankinson, Susan E.

AU - Hayes, Richard B.

AU - Henderson, Brian E.

AU - Hunter, David J.

AU - Hoover, Robert N.

AU - Johansson, Mattias

AU - Key, Timothy J.

AU - Khaw, Kay Tee

AU - Kolonel, Laurence N.

AU - Lagiou, Pagona

AU - Lee, I. Min

AU - LeMarchand, Loic

AU - Lund, Eiliv

AU - Ma, Jing

AU - Onland-Moret, N. Charlotte

AU - Overvad, Kim

AU - Rodriguez, Laudina

AU - Sacerdote, Carlotta

AU - Sánchez, Maria José

AU - Stampfer, Meir J.

AU - Stattin, Pär

AU - Stram, Daniel O.

AU - Thomas, Gilles

AU - Thun, Michael J.

AU - Tjønneland, Anne

AU - Trichopoulos, Dimitrios

AU - Tumino, Rosario

AU - Virtamo, Jarmo

AU - Weinstein, Stephanie J.

AU - Willett, Walter C.

AU - Yeager, Meredith

AU - Zhang, Shumin M.

AU - Kaaks, Rudolf

AU - Riboli, Elio

AU - Ziegler, Regina G.

AU - Kraft, Peter

PY - 2010/11

Y1 - 2010/11

N2 - 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.

AB - 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.

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U2 - 10.1158/1055-9965.EPI-10-0507

DO - 10.1158/1055-9965.EPI-10-0507

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JO - Cancer Epidemiology Biomarkers and Prevention

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