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Association between pre-diagnostic circulating adipokines and colorectal cancer and adenoma in the CLUE II cohort

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Abstract

Objective

Obesity is a known risk factor for colorectal cancer (CRC) and adenoma. Obese individuals have higher circulating concentrations of certain endocrine and immune factors produced by adipocytes thought to partially underlie the association between obesity and colorectal neoplasia. Thus, we evaluated the association of plasma concentrations of adiponectin, leptin, and soluble tumor necrosis factor receptor-2 (sTNFR2) with CRC and adenoma.

Methods

We ascertained 193 CRC cases and 193 matched controls, and 131 colorectal adenoma cases and 131 matched controls who had had an endoscopy nested in the CLUE II cohort of Washington County, MD. Plasma markers were measured using ELISA. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from conditional logistic regression for quartiles of the plasma markers separately for CRC and adenoma.

Results

Adjusting for leptin and adiponectin, sTNFR2 was positively associated with CRC only in men (Q4 vs. Q1: OR = 3.14, 95% CI 1.11–8.86), which was unchanged adjusting for BMI (3.46, 95% CI 1.19–10.06). Leptin and adiponectin were not associated with CRC risk overall or in men or women. Adiponectin, leptin, and sTNFR2 were not associated with adenoma risk overall or in men or women.

Conclusion

In this study, leptin and adiponectin were not associated with colorectal carcinogenesis and thus do not appear to underlie the association between obesity and colorectal carcinogenesis. sTNFR2, which we measured as a correlate of TNF-α, was positively associated with CRC in men adjusting for BMI, suggesting that TNF-α may influence colorectal carcinogenesis independent of adipocyte production.

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Acknowledgments

Dr. Kathy Helzlsouer and Judith Hoffman-Bolton for their assistance and support of this work. Cancer incidence data were provided by the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Maryland Department of Health, 201 W. Preston Street, Room 400, Baltimore, MD 21201. 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 helped support the availability of the cancer registry data. The datasets generated during and/or analysed during the current study are not publicly available but are available from the PI of CLUE, Dr. Kala Visvanathan, on reasonable request to the CLUE Steering Committee.

Funding

This research was supported by a grant from the American Institute for Cancer Research (Platz). Dr. Marrone was supported by National Cancer Institute grant T32 CA009314 (Platz). This work was further supported by NCI Cancer Center Support Grant P30 CA006973 (Nelson) and the Maryland Cigarette Restitution Fund at Johns Hopkins (Nelson).

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Authors and Affiliations

  1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Rm. E6133, Baltimore, MD, 21205, USA

    Michael T. Marrone, Jiayun Lu, Kala Visvanathan, Corinne E. Joshu & Elizabeth A. Platz

  2. Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins, Baltimore, MD, USA

    Kala Visvanathan, Corinne E. Joshu & Elizabeth A. Platz

  3. Department of Urology and the, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Elizabeth A. Platz

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  1. Michael T. Marrone
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  2. Jiayun Lu
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  4. Corinne E. Joshu
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  5. Elizabeth A. Platz
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Correspondence to Michael T. Marrone.

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Marrone, M.T., Lu, J., Visvanathan, K. et al. Association between pre-diagnostic circulating adipokines and colorectal cancer and adenoma in the CLUE II cohort. Cancer Causes Control 32, 871–881 (2021). https://doi.org/10.1007/s10552-021-01441-1

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  • DOI: https://doi.org/10.1007/s10552-021-01441-1

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