Meta-Analysis

. 2016 Apr 15;76(8):2288-2300.

doi: 10.1158/0008-5472.CAN-15-1551. Epub 2016 Feb 26.

A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk

Ruth C Travis¹, Paul N Appleby¹, Richard M Martin^{2

3}, Jeff M P Holly⁴, Demetrius Albanes⁵, Amanda Black⁵, H B As Bueno-de-Mesquita^{6

7}, June M Chan⁸, Chu Chen⁹, Maria-Dolores Chirlaque¹⁰, Michael B Cook⁵, Mélanie Deschasaux¹¹, Jenny L Donovan², Luigi Ferrucci¹², Pilar Galan¹¹, Graham G Giles¹³, Edward L Giovannucci^{14

15}, Marc J Gunter⁷, Laurel A Habel¹⁶, Freddie C Hamdy¹⁷, Kathy J Helzlsouer¹⁸, Serge Hercberg¹¹, Robert N Hoover⁵, Joseph A M J L Janssen¹⁹, Rudolf Kaaks²⁰, Tatsuhiko Kubo²¹, Loic Le Marchand²², E Jeffrey Metter^{12

23}, Kazuya Mikami²⁴, Joan K Morris²⁵, David E Neal²⁶, Marian L Neuhouser⁹, Kotaro Ozasa²⁷, Domenico Palli²⁸, Elizabeth A Platz²⁹, Michael Pollak³⁰, Alison J Price¹, Monique J Roobol³¹, Catherine Schaefer¹⁶, Jeannette M Schenk^{32

33}, Gianluca Severi^{13

34}, Meir J Stampfer^{14

35}, Pär Stattin³⁶, Akiko Tamakoshi³⁷, Catherine M Tangen³⁸, Mathilde Touvier¹¹, Nicholas J Wald²⁶, Noel S Weiss³⁴, Regina G Ziegler⁵, Timothy J Key^#¹, Naomi E Allen^#³⁹

Affiliations

¹ Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
² School of Social and Community Medicine, University of Bristol, Bristol, UK.
³ Medical Research Council/University of Bristol Integrative Epidemiology Unit, University of Bristol, and National Institute for Health Research, Bristol Biomedical Research Unit in Nutrition, Bristol, UK.
⁴ School of Clinical Science, Faculty of Medicine, University of Bristol, Bristol, UK.
⁵ Division of Cancer Epidemiology and Genetics, U.S. National Cancer Institute, Bethesda, MD, USA.
⁶ Dt. for Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Bilthoven, and Dt. of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands, and Dt. of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁷ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
⁸ Departments of Epidemiology & Biostatistics and Urology, University of California San Francisco, CA, USA.
⁹ Division of Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹⁰ Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, and CIBER Epidemiología y Salud Pública, Spain.
¹¹ Sorbonne Paris Cité Epidemiology and Biostatistics Research Center, Nutritional Epidemiology Research Team, Inserm U1153, Inra U1125, Cnam, University Paris 13, University Paris 5, University Paris 7, F-93017, Bobigny, France.
¹² Intramural Research Program, National Institute on Aging, Baltimore, MD, USA.
¹³ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, and Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Victoria, Australia.
¹⁴ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
¹⁵ Department of Nutrition and Department of Medicine, Harvard School of Public Health, Boston, MA, USA.
¹⁶ Division of Research, Kaiser Permanente, Northern California, Oakland, California, USA.
¹⁷ Nuffield Department of Surgery, University of Oxford, UK.
¹⁸ The Prevention and Research Center, Mercy Medical Center, Baltimore, MD, USA.
¹⁹ Erasmus MC, Dept Internal Medicine, Rotterdam, the Netherlands.
²⁰ Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
²¹ University of Occupational and Environmental Health, Kitakyushu, Japan.
²² University of Hawaii Cancer Center, Honolulu, HI, USA.
²³ Department of Neurology, University of Tennessee Health Science Center, Memphis, TN.
²⁴ Kyoto Prefectural University of Medicine, Kyoto, Japan.
²⁵ Wolfson Institute of Preventive Medicine, Queen Mary University of London, Charterhouse Square, London, UK.
²⁶ Department of Oncology, University of Cambridge, UK.
²⁷ Radiation Effects Research Foundation, Hiroshima, Japan.
²⁸ Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.
²⁹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
³⁰ Departments of Medicine and Oncology, McGill University, Montreal, QC, Canada.
³¹ Erasmus MC, Dept of Urology Rotterdam, the Netherlands.
³² Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
³³ Department of Epidemiology, University of Washington, Seattle, WA, USA.
³⁴ Human Genetics Foundation, Torino, Italy.
³⁵ Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
³⁶ Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
³⁷ Hokkaido University Graduate School of Medicine, Sapporo, Japan.
³⁸ SWOG Statistical Center, Fred Hutchinson Cancer Research Center, and Department of Biostatistics, University of Washington, Seattle, WA, USA.
³⁹ Clinical Trials Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

^# Contributed equally.

PMID: 26921328
PMCID: PMC4873385
DOI: 10.1158/0008-5472.CAN-15-1551

Meta-Analysis

A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk

Ruth C Travis et al. Cancer Res. 2016.

. 2016 Apr 15;76(8):2288-2300.

doi: 10.1158/0008-5472.CAN-15-1551. Epub 2016 Feb 26.

Authors

Affiliations

¹ Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
² School of Social and Community Medicine, University of Bristol, Bristol, UK.
³ Medical Research Council/University of Bristol Integrative Epidemiology Unit, University of Bristol, and National Institute for Health Research, Bristol Biomedical Research Unit in Nutrition, Bristol, UK.
⁴ School of Clinical Science, Faculty of Medicine, University of Bristol, Bristol, UK.
⁵ Division of Cancer Epidemiology and Genetics, U.S. National Cancer Institute, Bethesda, MD, USA.
⁶ Dt. for Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Bilthoven, and Dt. of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands, and Dt. of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁷ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
⁸ Departments of Epidemiology & Biostatistics and Urology, University of California San Francisco, CA, USA.
⁹ Division of Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹⁰ Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, and CIBER Epidemiología y Salud Pública, Spain.
¹¹ Sorbonne Paris Cité Epidemiology and Biostatistics Research Center, Nutritional Epidemiology Research Team, Inserm U1153, Inra U1125, Cnam, University Paris 13, University Paris 5, University Paris 7, F-93017, Bobigny, France.
¹² Intramural Research Program, National Institute on Aging, Baltimore, MD, USA.
¹³ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, and Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Victoria, Australia.
¹⁴ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
¹⁵ Department of Nutrition and Department of Medicine, Harvard School of Public Health, Boston, MA, USA.
¹⁶ Division of Research, Kaiser Permanente, Northern California, Oakland, California, USA.
¹⁷ Nuffield Department of Surgery, University of Oxford, UK.
¹⁸ The Prevention and Research Center, Mercy Medical Center, Baltimore, MD, USA.
¹⁹ Erasmus MC, Dept Internal Medicine, Rotterdam, the Netherlands.
²⁰ Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
²¹ University of Occupational and Environmental Health, Kitakyushu, Japan.
²² University of Hawaii Cancer Center, Honolulu, HI, USA.
²³ Department of Neurology, University of Tennessee Health Science Center, Memphis, TN.
²⁴ Kyoto Prefectural University of Medicine, Kyoto, Japan.
²⁵ Wolfson Institute of Preventive Medicine, Queen Mary University of London, Charterhouse Square, London, UK.
²⁶ Department of Oncology, University of Cambridge, UK.
²⁷ Radiation Effects Research Foundation, Hiroshima, Japan.
²⁸ Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.
²⁹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
³⁰ Departments of Medicine and Oncology, McGill University, Montreal, QC, Canada.
³¹ Erasmus MC, Dept of Urology Rotterdam, the Netherlands.
³² Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
³³ Department of Epidemiology, University of Washington, Seattle, WA, USA.
³⁴ Human Genetics Foundation, Torino, Italy.
³⁵ Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
³⁶ Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
³⁷ Hokkaido University Graduate School of Medicine, Sapporo, Japan.
³⁸ SWOG Statistical Center, Fred Hutchinson Cancer Research Center, and Department of Biostatistics, University of Washington, Seattle, WA, USA.
³⁹ Clinical Trials Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

^# Contributed equally.

PMID: 26921328
PMCID: PMC4873385
DOI: 10.1158/0008-5472.CAN-15-1551

Abstract

The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. Cancer Res; 76(8); 2288-300. ©2016 AACR.

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Figures

Figure 1. Odds ratios (95% confidence intervals) for prostate cancer associated with study-specific fifths of concentrations of selected insulin-like growth factors and their binding proteins in all studies and then restricted to prospective studies
Estimates are from logistic regression conditioned on the matching variables within each study and without mutual adjustment for the other analytes. Ptrend was calcuated by replacing the fifths of concentration with a continuous variable that was scored 0, 0.25, 0.5, 0.75 and 1 in the conditional logistic regression model. 80%le = 80 percentile; CI = confidence interval; P_tr = Ptrend.

**Figure 2. Study-specific odds ratios (95% confidence intervals) for prostate cancer associated with an 80 percentile increase in IGF-I**
Estimates are from logistic regression conditioned on the matching variables within each study and without mutual adjustment for the other analytes. Heterogeneity in linear trends between studies was tested by comparing the X² values for models with and without a (studies) × (linear trend) interaction term. For expansion of study names see Table 1.

**Figure 3. Odds ratios (95% confidence intervals) for prostate cancer associated with an 80 percentile increase in IGF-I in prospective studies, subdivided by various factors**
Estimates are from logistic regression conditioned on the matching variables within each study and without mutual adjustment for the other analytes. Odds ratios are for risk of prostate cancer overall, unless otherwise specified. Tests for heterogeneity for case-defined factors were obtained by fitting separate models for each subgroup and assuming independence of the ORs using a method analogous to a meta-analysis Tests for heterogeneity for non-case defined factors were assessed with a χ²-test of interaction between subgroup and the continuous trend test variable.

Figure 4. Odds ratios (95% confidence intervals) for aggressive prostate cancer associated with study-specific fifths of concentrations of selected insulin-like growth factors and their binding proteins
Estimates are from logistic regression conditioned on the matching variables within each study and without mutual adjustment for the other analytes.

See this image and copyright information in PMC

References

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A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk

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A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk

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