Investigating the association between anthropometry and colorectal cancer survival: a two-sample Mendelian randomization analysis.

Authors

Kanellopoulou A, Bouras E, Chan AT, Marchand LL, Wolk A, Wu AH, Gunter MJ, Nimptsch K, Haycock P, Lewis SJ, Martin RM, Zuber V, Phipps AI, Peters U, Van Duijnhoven FJB, Tsilidis KK

Affiliations

• Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece.
• Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
• Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
• Population Sciences in the Pacific Program, University of Hawaii Cancer Center, Honolulu, HI, United States.
• Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
• Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
• Molecular Epidemiology Research Group, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
• MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
• Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
• Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.

Abstract

BACKGROUND: Observational epidemiologic studies on the association of anthropometric traits and colorectal cancer (CRC) survival provide inconsistent results, and potential limitations prohibit the investigation of causality. We examined the associations between seven genetically predicted anthropometric traits [height, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-hip circumference ratio, birth weight and body fat percentage] and CRC-specific mortality among CRC cases using two-sample Mendelian randomization (MR).

METHODS: Analyses were performed using 16 964 CRC cases, out of which 4010 died due to their disease, from the Genetics and Epidemiology of Colorectal Cancer Consortium and Colon Cancer Family Registry. We further conducted stratified analyses by anatomical site and stage. We applied the inverse variance weighted approach, and sensitivity analyses were conducted to assess the impact of potential violations of MR assumptions and adjust for collider bias.

RESULTS: One standard deviation (SD 13.4 cm) higher genetically predicted levels of WC were associated with worse CRC survival [hazard ratio (HR); 1.22, 95% confidence interval (CI); 1.02-1.47]. Positive associations were further observed for a SD higher genetically predicted BMI (SD; 4.8 kg/m2, HR; 1.5, 95% CI; 1.15-1.95) and HC (SD; 9.2 cm, HR; 1.32, 95% CI; 1.02-1.73) and CRC-specific mortality in cases of stages II/III. The latter associations were generally robust to sensitivity analyses. Positive but imprecisely estimated associations were found for most other anthropometric traits.

CONCLUSIONS: Despite the limitations of cancer survival research, our findings support that CRC cases should avoid obesity. Further research should inform the development of recommendations targeting overweight/obesity management during cancer surveillance.