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Genetic Obesity Variants and Risk of Conventional Adenomas and Serrated Polyps

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Abstract

Background

Higher body mass index (BMI) is associated with increased risk of colorectal cancer. How genetically predicted BMI may be associated with colorectal cancer precursors is unknown.

Aims

Our objective was to quantify the association of genetically predicted and measured BMI with risk of colorectal cancer precursors.

Methods

We evaluated the association of genetically predicted and measured BMI with risk of conventional adenomas, serrated polyps, and synchronous polyps among 27,426 participants who had undergone at least one lower gastrointestinal endoscopy in the Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study. Genetic risk score was derived from 97 BMI-related single nucleotide polymorphisms. Multivariable logistic regression evaluated each polyp subtype compared to non-polyps.

Results

For conventional adenomas, the OR per 2-kg/m2 increase was 1.03 (95% CI, 1.01–1.04) for measured BMI and 0.98 (95% CI, 0.88–1.10) for genetically predicted BMI; for serrated polyps, the OR was 1.06 (95% CI, 1.04–1.08) and 1.04 (95% CI, 0.90–1.20), respectively; for synchronous polyps, the OR was 1.10 (95% CI, 1.07–1.13) and 1.09 (95% CI, 0.89–1.34), respectively. Genetically predicted BMI was associated with synchronous polyps in women (OR = 1.37, 95% CI: 1.05–1.79).

Conclusion

Genetically predicted BMI was not associated with colorectal cancer precursor lesions. The confidence intervals were wide and encompassed those for measured BMI, indicating that null findings may be due to insufficient power.

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Acknowledgments

We would like to thank the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data.

Funding

This work was supported by the American Cancer Society Mentored Research Scholar. Grant (MRSG-17–220-01—NEC to M.S.); by the U.S. National Institutes of Health (NIH) grants. [UM1 CA186107; P01 CA87969 to M.J. Stampfer; U01 CA186107 to M.J. Stampfer; P01 CA55075 to W.C. Willett; U01 CA167552 to W.C. Willett; K24 DK098311, R01 CA137178, R01 CA202704, R01 CA176726, to A.T.C.; K99 CA215314 and R00 CA215314 to M.S.; R01 CA67262, R01 CA49449, U01 CA176726]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA

    Alaina M. Bever, Amit D. Joshi & Kana Wu

  2. Harvard Medical School, Boston, MA, USA

    Alaina M. Bever

  3. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Dong Hang, Ming Ding, Edward L. Giovannucci & Mingyang Song

  4. Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Nanjing Medical University, Nanjing, China

    Dong Hang

  5. Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA

    Xiaosheng He, Amit D. Joshi, Kana Wu, Andrew T. Chan & Mingyang Song

  6. Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Xiaosheng He

  7. Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Andrew T. Chan & Edward L. Giovannucci

  8. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA

    Andrew T. Chan

  9. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Edward L. Giovannucci & Mingyang Song

Authors
  1. Alaina M. Bever
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  2. Dong Hang
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  3. Xiaosheng He
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  4. Amit D. Joshi
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  5. Ming Ding
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  6. Kana Wu
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  7. Andrew T. Chan
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  8. Edward L. Giovannucci
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  9. Mingyang Song
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Corresponding author

Correspondence to Mingyang Song.

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Conflict of interests

All authors report no competing interests and/or relevant financial interests in this manuscript.

Ethics approval

The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The study protocol was approved by the institutional review boards of Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required.

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Informed consent was obtained from all individual participants included in the study.

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Bever, A.M., Hang, D., He, X. et al. Genetic Obesity Variants and Risk of Conventional Adenomas and Serrated Polyps. Dig Dis Sci 67, 4078–4085 (2022). https://doi.org/10.1007/s10620-021-07193-x

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  • DOI: https://doi.org/10.1007/s10620-021-07193-x

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