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Serum ghrelin is associated with risk of colorectal adenocarcinomas in the ATBC study
  1. Gwen Murphy1,
  2. Amanda J Cross2,
  3. Sanford M Dawsey1,
  4. Frank Z Stanczyk3,
  5. Farin Kamangar1,4,
  6. Stephanie J Weinstein1,
  7. Philip R Taylor1,
  8. Satu Männistö5,
  9. Demetrius Albanes1,
  10. Christian C Abnet1,
  11. Neal D Freedman1
  1. 1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
  2. 2 Department of Epidemiology and Biostatistics, Imperial College London, London, UK
  3. 3 Departments of Obstetrics and Gynecology and Preventive Medicine, University of Southern California, Los Angeles, California, USA
  4. 4 Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, Maryland, USA
  5. 5 Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
  1. Correspondence to Gwen Murphy, Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, 9609 Medical Center Dr, 6E428, Bethesda, MD 20850, USA; murphygw{at}


Background Colorectal cancers are the third most common cancers in women and men in the USA. While dietary and lifestyle factors such as Western diet, physical inactivity and obesity have been linked to an increased risk of this malignancy, the mechanisms for these associations are unclear. GI hormones, including ghrelin, are involved in energy balance by mediating appetite and metabolism; however, the association between ghrelin and colorectal cancer has not been studied.

Methods We conducted a case–control study nested within the all-male Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish smokers (aged 50–69 years) to examine serum ghrelin concentration and colorectal cancer risk. Data from 284 colon and 239 rectal cancers and 523 controls (matched on age, date of blood draw and serum availability) were analysed. ORs and 95% CIs were calculated using multivariable (conditional) logistic regression.

Results Overall, low-serum ghrelin was significantly associated with increased risk of colorectal cancer (Q1 vs Q4: OR:1.57, 95% CI 1.05 to 2.34). For individuals developing tumours within 10 years of blood draw, those in the lowest quartile of serum ghrelin concentrations were statistically significantly more likely to develop colorectal cancers than those with higher serum ghrelin concentrations (OR: 10.86, 95% CI 5.01 to 23.55). However, for individuals with tumours developing more than 20 years after blood draw, low-serum ghrelin concentrations were associated with a decreased risk of colorectal cancer relative to those with the highest serum ghrelin concentrations (OR: 0.26, 95% CI 0.11 to 0.64).

Conclusion Low-serum ghrelin was associated with an increased colorectal cancer risk within 10 years of blood draw with a decreased risk for developing colorectal cancer more than 20 years after blood draw. These results suggest that ghrelin concentrations may vary across the carcinogenic process.

  • ghrelin
  • colon cancer
  • rectal cancer
  • gastrointestinal hormones

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  • Contributors GM: study conception and design, analysis, interpretation and writing of manuscript. AJC and NDF: study design and interpretation. CCA, SMD and FK: interpretation of results. FZS: lab analysis. SJW, SM and DA: provision of samples and interpretation.

  • Competing interests None declared.

  • Ethics approval National Cancer Institute, USA.

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