Body Mass Index and Other Anthropomorphic Variables in Relation to Risk of Colorectal Carcinoma Subtypes Classified by Tumor Differentiation Status
Authors: Borowsky Jennifer , Hanyuda Akiko , Nishihara Reiko , Song Mingyang , Lennerz Jochen K. , Meyerhardt Jeffrey A. , Chan Andrew T. , Fuchs Charles S. , Giovannucci Edward L. , Nowak Jonathan A. , Hamada Tsuyoshi , Ogino Shuji 
Published: June 2021

Metabolic energy dysregulation may affect intestinal epithelial cell homeostasis, and thus promote colorectal carcinogenesis. Yet, little is known about the association between obesity and enterocyte differentiation during tumor development.We hypothesized that an association between anthropomorphic measurements and colorectal carcinoma incidence might differ according to tumor histopathologic differentiation status. Anthropomorphic variables evaluated included Body Mass Index (BMI), Hip circumference (HC), Waist circumference (WC), and Waist‐Hip Ratio (WHR).Using data from the Nurses' Health Study and Health Professionals' Follow‐up Study, and performing duplication‐method Cox proportional hazard models, we prospectively examined an association between BMI, mean waist/hip circumference (WC/HC), and waist‐hip ratio (WHR) with the incidence of colorectal carcinoma subtypes classified by differentiation status. 120,813 participants were followed for 26 or 32 years and 1528 colorectal cancer cases with available tumor pathological data were documented.The association between BMI and colorectal cancer risk significantly differed depending on the presence or absence of poorly differentiated tumor foci (Pheterogeneity = 0.006). Higher BMI was associated with higher risk of colorectal carcinoma without poorly differentiated foci (≥30.0 vs. 18.5–22.4 kg/m2: multivariable‐adjusted hazard ratio, 1.87; 95% confidence interval, 1.49–2.34; Ptrend <0.001), but not with risk of carcinoma with poorly‐differentiated foci (Ptrend = 0.56). While in men, high WC, HC, and WHR were associated with overall incidence of colorectal carcinoma (Ptrend ≤ 0.01), there was no statistically significant association between these variables and tumor differentiation status (Pheterogeneity >0.27). Furthermore, the association between anthropomorphic variables and colorectal carcinoma did not differ significantly by overall tumor grade, mucinous differentiation, or the presence of a signet‐ring‐cell component (PHeterogeneity > 0.03, with the adjusted α of 0.01). The differential association of BMI with tumor differentiation appeared to be consistent in strata of tumor microsatellite instability and fatty acid synthase (FASN) expression, although statistical power was limited.Whilst BMI was associated with increased risk of the colorectal cancer subtype lacking poorly differentiated foci, there was no independent association between tumor differentiation and measures of central adiposity. Our findings suggest that the carcinogenic effect of generalized excess body adiposity may be stronger for tumors that retain greater degrees of intestinal differentiation.Support or Funding InformationThis work was supported by U.S. National Institutes of Health (NIH) grants (P01 CA87969 to M.J. Stampfer; UM1 CA186107 to M.J. Stampfer; P01 CA55075 to W.C. Willett; UM1 CA167552 to W.C. Willett; U01 CA167552 to W.C. Willett and L.A. Mucci; P50 CA127003 to C.S.F.; R01 CA118553 to C.S.F.; R01 CA169141 to C.S.F.; R01 CA137178 to A.T.C.; K24 DK098311 to A.T.C.; R35 CA197735 to S.O.; R01 CA151993 to S.O.; K07 CA190673 to R.N.; and K07 CA188126 to X.Z.); by Nodal Award from the Dana‐Farber Harvard Cancer Center (to S.O.); and by grants from the Project P Fund, The Friends of the Dana‐Farber Cancer Institute, Bennett Family Fund, and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance, and by Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant (to C.S.F. and M.Gi.). J.B. was supported by the Australia Awards‐Endeavour Scholarships and Fellowships Program. K.K. was supported by grants from Overseas Research Fellowship (JP2017–775) from Japan Society for the Promotion of Science. T.H. was supported by a fellowship grant from the Mitsukoshi Health and Welfare Foundation.T.H. was supported by a fellowship grant from the Mitsukoshi Health and Welfare Foundation. L.L. was supported by a scholarship grant from Chinese Scholarship Council and a fellowship grant from Huazhong University of Science and Technology. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.