title: Body mass index and risk of colorectal cancer according to tumor lymphocytic infiltrate.
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.
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hanyuda
authors.affiliation: Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.|Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.|Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Shuji
authors.initials: S
authors.lastname: Ogino
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Zhi Rong
authors.initials: ZR
authors.lastname: Qian
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.|Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.|Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Reiko
authors.initials: R
authors.lastname: Nishihara
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.|Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.|Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.|Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Song
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Mima
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.|Division of Pathology, Cancer Institute, JFCR, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Inamura
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Masugi
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Kana
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Meyerhardt
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.|Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.|Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.|Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.|Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000368:Aged; D015415:Biomarkers; D015992:Body Mass Index; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015897:Comorbidity; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D060787:Neoplasm Grading; D012042:Registries; D012306:Risk; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D015415:Biomarkers
keywords: body mass index; colorectal carcinoma; lymphocytic reaction; molecular pathological epidemiology