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

Akiko Hanyuda, Shuji Ogino, Zhi Rong Qian, Reiko Nishihara, Mingyang Song, Kosuke Mima, Kentaro Inamura, Yohei Masugi, Kana Wu, Jeffrey A. Meyerhardt, Andrew T. Chan, Charles S. Fuchs, Edward L. Giovannucci, Yin Cao

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)854-868
Number of pages15
JournalInternational Journal of Cancer
Issue number4
Publication statusPublished - 2016 Aug 15
Externally publishedYes


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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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