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    Rights statement: This is the peer reviewed version of the following article: Bonilla, C. et al. the PRACTICAL consortium, Lathrop, M., Martin, R. M. and Holly, J. M. P. (2016), Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels. Int. J. Cancer, 139: 1520–1533. doi: 10.1002/ijc.30206 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/jpim.12206/abstract This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.

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Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: genetic variants as instruments for circulating levels

Research output: Contribution to Journal/Magazine › Journal article › peer-review

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Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: genetic variants as instruments for circulating levels. / Bonilla, Carolina; Lewis, Sarah J.; Rowlands, Mari-Anne et al.
In: International Journal of Cancer, Vol. 139, No. 7, 01.10.2016, p. 1520-1533.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Bonilla, C, Lewis, SJ, Rowlands, M-A, Gaunt, TR, Smith, GD, Gunnell, D, Palmer, T, Donovan, JL, Hamdy, FC, Neal, DE, Eeles, R, Easton, D, Kote-Jarai, Z, Olama, AAA, Benlloch, S, Muir, K, Giles, GG, Wiklund, F, Gronberg, H, Haiman, CA, Schleutker, J, Nordestgaard, BG, Travis, RC, Pashayan, N, Khaw, K-T, Stanford, JL, Blot, WJ, Thibodeau, S, Maier, C, Kibel, AS, Cybulski, C, Cannon-Albright, L, Brenner, H, Park, J, Kaneva, R, Batra, J, Teixeira, MR, Pandha, H, Lathrop, M, Martin, RM, Holly, JMP & PRACTICAL consortium 2016, 'Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: genetic variants as instruments for circulating levels', International Journal of Cancer, vol. 139, no. 7, pp. 1520-1533. https://doi.org/10.1002/ijc.30206

APA

Bonilla, C., Lewis, S. J., Rowlands, M-A., Gaunt, T. R., Smith, G. D., Gunnell, D., Palmer, T., Donovan, J. L., Hamdy, F. C., Neal, D. E., Eeles, R., Easton, D., Kote-Jarai, Z., Olama, A. A. A., Benlloch, S., Muir, K., Giles, G. G., Wiklund, F., Gronberg, H., ... PRACTICAL consortium (2016). Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: genetic variants as instruments for circulating levels. International Journal of Cancer, 139(7), 1520-1533. https://doi.org/10.1002/ijc.30206

Vancouver

Bonilla C, Lewis SJ, Rowlands M-A, Gaunt TR, Smith GD, Gunnell D et al. Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: genetic variants as instruments for circulating levels. International Journal of Cancer. 2016 Oct 1;139(7):1520-1533. Epub 2016 May 26. doi: 10.1002/ijc.30206

Author

Bonilla, Carolina ; Lewis, Sarah J. ; Rowlands, Mari-Anne et al. / Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization : genetic variants as instruments for circulating levels. In: International Journal of Cancer. 2016 ; Vol. 139, No. 7. pp. 1520-1533.

Bibtex

@article{1bbec454e325404cbe5c385b6c3adfd1,
title = "Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: genetic variants as instruments for circulating levels",
abstract = "Circulating insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome-wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N∼900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs high (≥ 7) Gleason grade, localised vs advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF-II and IGFBP-3, less so for IGF-I. Rs11977526 was associated with high (vs low) Gleason grade (OR per IGF-II/IGFBP-3 level-raising allele 1.05; 95% CI 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF-II (∼265 ng/ml) on risk of high vs low grade disease as 1.14 (95% CI 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker. This article is protected by copyright. All rights reserved.",
author = "Carolina Bonilla and Lewis, {Sarah J.} and Mari-Anne Rowlands and Gaunt, {Tom R.} and Smith, {George Davey} and David Gunnell and Tom Palmer and Donovan, {Jenny L.} and Hamdy, {Freddie C.} and Neal, {David E.} and Rosalind Eeles and Doug Easton and Zsofia Kote-Jarai and Olama, {Ali Amin Al} and Sara Benlloch and Kenneth Muir and Giles, {Graham G.} and Fredrik Wiklund and Henrik Gronberg and Haiman, {Christopher A.} and Johanna Schleutker and Nordestgaard, {B{\o}rge G.} and Travis, {Ruth C.} and Nora Pashayan and Kay-Tee Khaw and Stanford, {Janet L.} and Blot, {William J.} and Stephen Thibodeau and Christiane Maier and Kibel, {Adam S.} and Cezary Cybulski and Lisa Cannon-Albright and Hermann Brenner and Jong Park and Radka Kaneva and Jyotsna Batra and Teixeira, {Manuel R.} and Hardev Pandha and Mark Lathrop and Martin, {Richard M.} and Holly, {Jeff M. P.} and {PRACTICAL consortium}",
note = "This is the peer reviewed version of the following article: Bonilla, C., Lewis, S. J., Rowlands, M.-A., Gaunt, T. R., Davey Smith, G., Gunnell, D., Palmer, T., Donovan, J. L., Hamdy, F. C., Neal, D. E., Eeles, R., Easton, D., Kote-Jarai, Z., Al Olama, A. A., Benlloch, S., Muir, K., Giles, G. G., Wiklund, F., Gr{\"o}nberg, H., Haiman, C. A., Schleutker, J., Nordestgaard, B. G., Travis, R. C., Pashayan, N., Khaw, K.-T., Stanford, J. L., Blot, W. J., Thibodeau, S., Maier, C., Kibel, A. S., Cybulski, C., Cannon-Albright, L., Brenner, H., Park, J., Kaneva, R., Batra, J., Teixeira, M. R., Pandha, H., the PRACTICAL consortium, Lathrop, M., Martin, R. M. and Holly, J. M. P. (2016), Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels. Int. J. Cancer, 139: 1520–1533. doi: 10.1002/ijc.30206 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/jpim.12206/abstract This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.",
year = "2016",
month = oct,
day = "1",
doi = "10.1002/ijc.30206",
language = "English",
volume = "139",
pages = "1520--1533",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "7",

}

RIS

TY - JOUR

T1 - Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization

T2 - genetic variants as instruments for circulating levels

AU - Bonilla, Carolina

AU - Lewis, Sarah J.

AU - Rowlands, Mari-Anne

AU - Gaunt, Tom R.

AU - Smith, George Davey

AU - Gunnell, David

AU - Palmer, Tom

AU - Donovan, Jenny L.

AU - Hamdy, Freddie C.

AU - Neal, David E.

AU - Eeles, Rosalind

AU - Easton, Doug

AU - Kote-Jarai, Zsofia

AU - Olama, Ali Amin Al

AU - Benlloch, Sara

AU - Muir, Kenneth

AU - Giles, Graham G.

AU - Wiklund, Fredrik

AU - Gronberg, Henrik

AU - Haiman, Christopher A.

AU - Schleutker, Johanna

AU - Nordestgaard, Børge G.

AU - Travis, Ruth C.

AU - Pashayan, Nora

AU - Khaw, Kay-Tee

AU - Stanford, Janet L.

AU - Blot, William J.

AU - Thibodeau, Stephen

AU - Maier, Christiane

AU - Kibel, Adam S.

AU - Cybulski, Cezary

AU - Cannon-Albright, Lisa

AU - Brenner, Hermann

AU - Park, Jong

AU - Kaneva, Radka

AU - Batra, Jyotsna

AU - Teixeira, Manuel R.

AU - Pandha, Hardev

AU - Lathrop, Mark

AU - Martin, Richard M.

AU - Holly, Jeff M. P.

AU - PRACTICAL consortium

N1 - This is the peer reviewed version of the following article: Bonilla, C., Lewis, S. J., Rowlands, M.-A., Gaunt, T. R., Davey Smith, G., Gunnell, D., Palmer, T., Donovan, J. L., Hamdy, F. C., Neal, D. E., Eeles, R., Easton, D., Kote-Jarai, Z., Al Olama, A. A., Benlloch, S., Muir, K., Giles, G. G., Wiklund, F., Grönberg, H., Haiman, C. A., Schleutker, J., Nordestgaard, B. G., Travis, R. C., Pashayan, N., Khaw, K.-T., Stanford, J. L., Blot, W. J., Thibodeau, S., Maier, C., Kibel, A. S., Cybulski, C., Cannon-Albright, L., Brenner, H., Park, J., Kaneva, R., Batra, J., Teixeira, M. R., Pandha, H., the PRACTICAL consortium, Lathrop, M., Martin, R. M. and Holly, J. M. P. (2016), Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels. Int. J. Cancer, 139: 1520–1533. doi: 10.1002/ijc.30206 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/jpim.12206/abstract This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Circulating insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome-wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N∼900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs high (≥ 7) Gleason grade, localised vs advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF-II and IGFBP-3, less so for IGF-I. Rs11977526 was associated with high (vs low) Gleason grade (OR per IGF-II/IGFBP-3 level-raising allele 1.05; 95% CI 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF-II (∼265 ng/ml) on risk of high vs low grade disease as 1.14 (95% CI 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker. This article is protected by copyright. All rights reserved.

AB - Circulating insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome-wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N∼900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs high (≥ 7) Gleason grade, localised vs advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF-II and IGFBP-3, less so for IGF-I. Rs11977526 was associated with high (vs low) Gleason grade (OR per IGF-II/IGFBP-3 level-raising allele 1.05; 95% CI 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF-II (∼265 ng/ml) on risk of high vs low grade disease as 1.14 (95% CI 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker. This article is protected by copyright. All rights reserved.

U2 - 10.1002/ijc.30206

DO - 10.1002/ijc.30206

M3 - Journal article

C2 - 27225428

VL - 139

SP - 1520

EP - 1533

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 7

ER -