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Pre-diagnosis insulin-like growth factor-I and risk of epithelial invasive ovarian cancer by histological subtypes: A collaborative re-analysis from the Ovarian Cancer Cohort Consortium

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Abstract

Purpose

Biologic evidence suggests that the Insulin-like growth factor (IGF)-family may be involved in the etiology of epithelial invasive ovarian cancer (EOC). However, prospective studies investigating the role of IGF-I in ovarian carcinogenesis have yielded conflicting results.

Methods

We pooled and harmonized data from 6 case–control studies nested within the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis IGF-I concentrations and subsequent risk of EOC. We evaluated IGF-I concentrations and risk of EOC overall and by tumor subtype (defined by histology, grade, stage) in 1,270 cases and 2,907 matched controls. Multivariable conditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI).

Results

Doubling of IGF-I concentration was associated with significantly lower risk of overall EOC [ORlog2 = 0.82; CI 0.72–0.93]. We observed no heterogeneity by tumor characteristics (e.g., histology, p het = 0.62), menopausal status at blood collection (p het = 0.79), or age at diagnosis (p het = 0.60).

Conclusions

These results suggest that IGF-I concentrations are inversely associated with EOC risk, independent of histological phenotype. Future prospective research should consider potential mechanisms for this association, including, considering other members of the IGF-family to better characterize the role of IGF-signaling in the etiology of EOC.

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Acknowledgments

We thank the participants and staff of the Nurses’ Health Study and Nurses’ Health Study II for their valuable contributions as well as the following state cancer registries for their help: Alabama, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Nebraska, New Hampshire, New Jersey, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Tennessee, Texas, Virginia, Washington, and Wyoming. We thank the participants and staff of CLUE II for their contributions as well as the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Department of Health and Mental Hygiene, 201W. Preston Street, Room 400, Baltimore, MD 21201, http://phpa.dhmh.maryland.gov/cancer, 410-767-4055. We acknowledge the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries of the Centers for Disease Control and Prevention for the funds that support the collection and availability of the cancer registry data.

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Corresponding author

Correspondence to Renée T. Fortner.

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No potential conflicts of interest were disclosed.

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The authors assume full responsibility for analyses and interpretation of these data.

Grant Support

The OC3 is supported by Department of Defense Ovarian Cancer Research Program Grant No. W81XWH-12-1-0561. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada; PI13/01162 to EPIC-Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). Support was provided by the following National Institutes of Health/NCI grants: R01 CA120061 (Finnish Maternity Cohort); UM1 CA186107, P01 CA87969, UM1 CA176726, and R01 CA67262 (Nurses’ Health Study, Nurses’ Health Study II); HL043851, HL080467, and HL099355 (Women’s Health Study). CLUEII was supported by National Cancer Institute grant numbers: CA-97857, CA-86308; Grant sponsor: M. Jean Goutal (donation): Grant sponsors: The Woodrow Wilson Foundation/Johnson and Johnson, The Lloyds TSB Charitable Foundation for the Channel Islands. RT Fortner was supported by a Marie Curie International Incoming Fellowship of the European Commission’s Seventh Framework Programme (MC-IIF-623984).

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Ose, J., Schock, H., Poole, E.M. et al. Pre-diagnosis insulin-like growth factor-I and risk of epithelial invasive ovarian cancer by histological subtypes: A collaborative re-analysis from the Ovarian Cancer Cohort Consortium. Cancer Causes Control 28, 429–435 (2017). https://doi.org/10.1007/s10552-017-0852-8

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