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Original research
Metabolic syndrome, metabolic comorbid conditions and risk of early-onset colorectal cancer
  1. Hanyu Chen1,2,
  2. Xiaobin Zheng1,3,4,
  3. Xiaoyu Zong1,
  4. Zitong Li1,5,
  5. Na Li1,6,
  6. Jinhee Hur7,
  7. Cassandra DL Fritz1,8,
  8. William Chapman Jr9,
  9. Katelin B Nickel10,
  10. Andrew Tipping10,
  11. Graham A Colditz1,11,
  12. Edward L Giovannucci7,12,
  13. Margaret A Olsen1,10,
  14. Ryan C Fields11,13,
  15. Yin Cao1,8,11
  1. 1Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine in Saint Louis, Saint Louis, Missouri, USA
  2. 2Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
  3. 3Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
  4. 4Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
  5. 5Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  6. 6Brown School at Washington University in St. Louis, Saint Louis, Missouri, USA
  7. 7Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  8. 8Division of Gastroenterology, Department of Medicine, Washington University School of Medicine in Saint Louis, Saint Louis, Missouri, USA
  9. 9Department of Surgery, Washington University School of Medicine in Saint Louis, Saint Louis, Missouri, USA
  10. 10Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine in Saint Louis, Saint Louis, Missouri, USA
  11. 11Alvin J. Siteman Cancer Center, Washington University School of Medicine in Saint Louis, Saint Louis, Missouri, USA
  12. 12Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  13. 13Section of Surgical Oncology, Department of Surgery, Washington University School of Medicine in Saint Louis, Saint Louis, Missouri, USA
  1. Correspondence to Dr Yin Cao, Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine in Saint Louis, Saint Louis, MO 63110, USA; yin.cao{at}wustl.edu

Abstract

Objective Factors that lead to metabolic dysregulation are associated with increased risk of early-onset colorectal cancer (CRC diagnosed under age 50). However, the association between metabolic syndrome (MetS) and early-onset CRC remains unexamined.

Design We conducted a nested case–control study among participants aged 18–64 in the IBM MarketScan Commercial Database (2006–2015). Incident CRC was identified using pathologist-coded International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, and controls were frequency matched. MetS was defined as presence of ≥3 conditions among obesity, hypertension, hyperlipidaemia and hyperglycaemia/type 2 diabetes, based on ICD-9-CM and use of medications. Multivariable logistic regressions were used to estimate ORs and 95% CIs.

Results MetS was associated with increased risk of early-onset CRC (n=4673; multivariable adjusted OR 1.25; 95% CI 1.09 to 1.43), similar to CRC diagnosed at age 50–64 (n=14 928; OR 1.21; 95% CI 1.15 to 1.27). Compared with individuals without a metabolic comorbid condition, those with 1, 2 or ≥3 conditions had a 9% (1.09; 95% CI 1.00 to 1.17), 12% (1.12; 95% CI 1.01 to 1.24) and 31% (1.31; 95% CI 1.13 to 1.51) higher risk of early-onset CRC (ptrend <0.001). No associations were observed for one or two metabolic comorbid conditions and CRC diagnosed at age 50–64. These positive associations were driven by proximal (OR per condition 1.14; 95% CI 1.06 to 1.23) and distal colon cancer (OR 1.09; 95% CI 1.00 to 1.18), but not rectal cancer (OR 1.03; 95% CI 0.97 to 1.09).

Conclusions Metabolic dysregulation was associated with increased risk of early-onset CRC, driven by proximal and distal colon cancer, thus at least in part contribute to the rising incidence of early-onset CRC.

  • colorectal cancer
  • cancer epidemiology
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Footnotes

  • HC, XBZ and XYZ contributed equally.

  • Contributors HC and YC had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. HC, XBZ, ELG, MAO, and YC helped in study concept and design. KBN, AT, MAO and YC helped in acquisition of data. All coauthors performed analysis and interpretation of data. Drafting of the manuscript was done by HC, XBZ, XYZ, ZL, NL and YC. Critical revision of the manuscript for important intellectual content was done by all coauthors. HC, XYZ, ZL and YC helped in statistical analysis. YC helped in obtaining funding. Administrative, technical or material support was provided by MAO and YC. Study supervision was done by YC.

  • Funding This work was supported by US National Institutes of Health (NIH) grant P30CA091842. The Center for Administrative Data Research is supported in part by the Washington University Institute of Clinical and Translational Sciences grant UL1 TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the NIH and Grant Number R24 HS19455 through the Agency for Healthcare Research and Quality (AHRQ). HC is a self-funded visiting scholar without financial support from the First Affiliated Hospital of China Medical University. XBZ was supported by the International Program for PhD Candidates, Sun Yat-sen University (grant/award number: NA). ZL is a self-funded visiting scholar without financial support from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. CDF was supported by T32 DK007130.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data may be obtained from a third party and are not publicly available.

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