Waist Circumference, a Body Shape Index, and Molecular Subtypes of Colorectal Cancer: A Pooled Analysis of Four Cohort Studies.

Authors

Chalitsios CV, Markozannes G, Papagiannopoulos C, Aglago EK, Berndt SI, Buchanan DD, Campbell PT, Cao Y, Chan AT, Dimou N, Drew DA, French AJ, Georgeson P, Giannakis M, Gruber SB, Gunter MJ, Harrison TA, Hoffmeister M, Hsu L, Huang WY, ...show more Hullar MAJ, Huyghe JR, Lynch BM, Moreno V, Newton CC, Nowak JA, Obón-Santacana M, Ogino S, Qu C, Schmit SL, Steinfelder RS, Sun W, Thomas CE, Toland AE, Trinh QM, Ugai T, Um CY, Van Guelpen B, Zaidi SH, Murphy N, Peters U, Phipps AI, Tsilidis KK

Affiliations

• Department of Hygiene and Epidemiology, University of Ioannina, Ioannina, Greece.
• Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
• Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
• Colorectal Oncogenomics Group, Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Parkville, Australia.
• Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
• Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, Missouri.
• Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
• Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
• Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
• Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Abstract

BACKGROUND: Waist circumference (WC) and its allometric counterpart, "a body shape index" (ABSI), are risk factors for colorectal cancer; however, it is uncertain whether associations with these body measurements are limited to specific molecular subtypes of the disease.

METHODS: Data from 2,772 colorectal cancer cases and 3,521 controls were pooled from four cohort studies within the Genetics and Epidemiology of Colorectal Cancer Consortium. Four molecular markers (BRAF mutation, KRAS mutation, CpG island methylator phenotype, and microsatellite instability) were analyzed individually and in combination (Jass types). Multivariable logistic and multinomial logistic models were used to assess the associations of WC and ABSI with overall colorectal cancer risk and, in case-only analyses, to evaluate heterogeneity by molecular subtype, respectively.

RESULTS: Higher WC (ORper 5 cm = 1.06, 95% confidence interval, 1.04-1.09) and ABSI (ORper 1-SD = 1.07, 95% confidence interval, 1.00-1.14) were associated with elevated colorectal cancer risk. There was no evidence of heterogeneity between the molecular subtypes. No difference was observed regarding the influence of WC and ABSI on the four major molecular markers in proximal colon, distal colon, and rectal cancers, as well as in early- and late-onset colorectal cancers. Associations did not differ in the Jass-type analysis.

CONCLUSIONS: Higher WC and ABSI were associated with elevated colorectal cancer risk; however, they do not differentially influence all four major molecular mutations involved in colorectal carcinogenesis but underscore the importance of maintaining a healthy body weight in colorectal cancer prevention.

IMPACT: The proposed results have potential utility in colorectal cancer prevention.