Body mass index and risk of colorectal carcinoma subtypes classified by tumor differentiation status

Akiko Hanyuda; Yin Cao; Tsuyoshi Hamada; Jonathan A Nowak; Zhi Rong Qian; Yohei Masugi; Annacarolina da Silva; Li Liu; Keisuke Kosumi; Thing Rinda Soong; Iny Jhun; Kana Wu; Xuehong Zhang; Mingyang Song; Jeffrey A Meyerhardt; Andrew T Chan; Charles S Fuchs; Edward L Giovannucci; Shuji Ogino; Reiko Nishihara

doi:10.1007/s10654-017-0254-y

Body mass index and risk of colorectal carcinoma subtypes classified by tumor differentiation status

Eur J Epidemiol. 2017 May;32(5):393-407. doi: 10.1007/s10654-017-0254-y. Epub 2017 May 16.

Authors

Akiko Hanyuda^{1

2}, Yin Cao^{1

3

4}, Tsuyoshi Hamada⁵, Jonathan A Nowak⁶, Zhi Rong Qian^{5

7}, Yohei Masugi⁵, Annacarolina da Silva⁵, Li Liu^{1

5}, Keisuke Kosumi⁵, Thing Rinda Soong⁶, Iny Jhun⁶, Kana Wu^{1

7}, Xuehong Zhang⁸, Mingyang Song^{1

3

4}, Jeffrey A Meyerhardt⁵, Andrew T Chan^{3

4

8

9}, Charles S Fuchs^{5

8}, Edward L Giovannucci^{1

8

10}, Shuji Ogino^{11

12

13

14}, Reiko Nishihara^{15

16

17

18

19

20}

Affiliations

¹ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
² Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
³ Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁴ Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁵ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
⁶ Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁸ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁹ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹¹ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. shuji_ogino@dfci.harvard.edu.
¹² Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. shuji_ogino@dfci.harvard.edu.
¹³ Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA. shuji_ogino@dfci.harvard.edu.
¹⁴ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. shuji_ogino@dfci.harvard.edu.
¹⁵ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. rnishiha@hsph.harvard.edu.
¹⁶ Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. rnishiha@hsph.harvard.edu.
¹⁷ Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA. rnishiha@hsph.harvard.edu.
¹⁸ Broad Institute of MIT and Harvard, Cambridge, MA, USA. rnishiha@hsph.harvard.edu.
¹⁹ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. rnishiha@hsph.harvard.edu.
²⁰ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. rnishiha@hsph.harvard.edu.

Abstract

Previous studies suggest that abnormal energy balance status may dysregulate intestinal epithelial homeostasis and promote colorectal carcinogenesis, yet little is known about how host energy balance and obesity influence enterocyte differentiation during carcinogenesis. We hypothesized that the association between high body mass index (BMI) and colorectal carcinoma incidence might differ according to tumor histopathologic differentiation status. Using databases of the Nurses' Health Study and Health Professionals Follow-up Study, and duplication-method Cox proportional hazards models, we prospectively examined an association between BMI and the incidence of colorectal carcinoma subtypes classified by differentiation features. 120,813 participants were followed for 26 or 32 years and 1528 rectal and colon 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 foci (P_{heterogeneity} = 0.006). Higher BMI was associated with a 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; P_trend < 0.001), but not with risk of carcinoma with poorly-differentiated foci (P_trend = 0.56). This differential association appeared to be consistent in strata of tumor microsatellite instability or FASN expression status, although the statistical power was limited. The association between BMI and colorectal carcinoma risk did not significantly differ by overall tumor differentiation, mucinous differentiation, or signet ring cell component (P_{heterogeneity} > 0.03, with the adjusted α of 0.01). High BMI was associated with risk of colorectal cancer subtype containing no poorly-differentiated focus. Our findings suggest that carcinogenic influence of excess energy balance might be stronger for tumors that retain better intestinal differentiation throughout the tumor areas.

Keywords: Epigenetics; Glandular epithelium; Metabolism; Molecular pathological epidemiology; Overweight; Stem cell.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Body Mass Index*
Cell Differentiation / genetics*
Colorectal Neoplasms / epidemiology
Colorectal Neoplasms / genetics
Colorectal Neoplasms / pathology*
Epigenomics
Follow-Up Studies
Humans
Incidence
Microsatellite Instability
Molecular Epidemiology
Obesity* / complications
Pathology, Molecular
Risk Factors
United States / epidemiology

Abstract

Publication types

MeSH terms

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