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Int J Cancer. 2016 Aug 15;139(4):854-68. doi: 10.1002/ijc.30122. Epub 2016 May 10.

Body mass index and risk of colorectal cancer according to tumor lymphocytic infiltrate.

Hanyuda A1, Ogino S2,3,4,5, Qian ZR4, Nishihara R1,4,5,6, Song M1,4,7,8, Mima K4, Inamura K4,9, Masugi Y4, Wu K1, Meyerhardt JA4, Chan AT4,7,8,10, Fuchs CS3,10, Giovannucci EL1,5,10, Cao Y1,7,8.

Author information

1
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
2
Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
3
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
4
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
5
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
6
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA.
7
Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
8
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
9
Division of Pathology, Cancer Institute, JFCR, Tokyo, Japan.
10
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Abstract

Higher body mass index (BMI), higher body adiposity and obesity have been associated with increased risk of colorectal cancer. Evidence suggests that excess energy balance may influence systemic immune and inflammatory status. Thus, we hypothesized that the positive association between BMI and colorectal cancer risk might differ according to colorectal carcinoma subtypes according to levels of histopathological lymphocytic reaction to tumor. We collected biennial questionnaire data on weight and baseline height information in two prospective cohort studies, the Nurses' Health Study (1980-2010) and the Health Professionals Follow-up Study (1986-2010). Utilizing duplication-method Cox proportional hazards regression models, we prospectively assessed the association between BMI and risk of colorectal cancer subtypes according to the degree of Crohn's-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, tumor-infiltrating lymphocytes, the overall lymphocytic reaction score, or T-cell [CD3(+) , CD8(+) , CD45RO (PTPRC)(+) or FOXP3(+) ] density in tumor tissue. Statistical significance level was adjusted for multiple hypotheses testing by Bonferroni correction. During follow up of 1,708,029 men and women (over 3,346,752 person-years), we documented 1,436 incident rectal and colon cancer cases with available formalin-fixed paraffin-embedded tumor tissue materials and pathological immunity data. BMI was significantly associated with higher risk of overall colorectal cancer (Ptrend  < 0.001); however, the association of BMI with colorectal carcinoma risk did not significantly differ by the level of lymphocytic reaction or T-cell infiltration in tumor tissue status (Pheterogeneity  > 0.10). BMI may be associated with risk of colorectal cancer regardless of levels of lymphocytic response to tumor.

KEYWORDS:

body mass index; colorectal carcinoma; lymphocytic reaction; molecular pathological epidemiology

PMID:
27037951
PMCID:
PMC5328655
DOI:
10.1002/ijc.30122
[Indexed for MEDLINE]
Free PMC Article

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