Abstract B11: Asthma and risk of colorectal cancer according to tumor immunity and molecular subtypes
Authors: Yu Li, Mingyang Song, Reiko Nishihara, Zhi Rong Qian, Raphaelle Varraso, Kentaro Inamura, Yohei Masugi, Edward L. Giovannucci, Molin Wang, Carlos A. Camargo, Charles S. Fuchs, Andrew T. Chan, Shuji Ogino, Yin Cao
Journal: Cancer Research (2017)

Abstract Background: Immune cell infiltration are important prognostic factors for colorectal cancer. Immunologic disorders such as asthma may influence cancer risks. However, no study has examined the association between history of asthma and colorectal cancer risks according to immune cell density. Methods: We collected data on self-reported and confirmed asthma, allergic rhinitis, COPD, as well as colorectal cancer during follow-up of 118,161 women of the Nurses' Health Study and 48,923 men of the Health Professional Follow-up Study. We subtyped 768 cancer cases according to densities of CD3+, CD8+, CD45RO+, and FOXP3+ T cells, and degree of tumor-infiltrating lymphocytes, intratumoral periglandular reaction, peritumoral lymphocytic reaction, and Crohn's-like lymphoid reaction in cancer using archival cancer tissue. Duplication-method Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the association between asthma and colorectal cancer according to subgroups of immune infiltration. Likelihood ratio tests were used to assess statistical trend for etiologic heterogeneity across ordinal cancer subgroups. Results: History of self-reported asthma was not associated with overall risk of colorectal cancer (multivariable hazard ratio=0.97, 95% CI, 0.87-1.09); but there was a non-significant differential association according to CD45RO+ cell density (p for heterogeneity=0.05) and CD8+ cell density (p for heterogeneity=0.08). The HR for the association of asthma and risk of colorectal cancer decreased from 1.26 (95% CI, 0.78, 2.04) for colorectal cancer with the lowest density of CD45RO+ cell (Quartile 1) to 0.61 (95% CI, 0.32, 1.16) for colorectal cancer with the highest density of CD45RO+ cell (Quartile 4). The HR for asthma and risk of colorectal cancer decreased from 1.37 (95% CI, 0.85, 2.22) for colorectal cancer with the lowest CD8+ cell density (Quartile 1) to 0.69 (95% CI, 0.35, 1.36) for colorectal cancer with the highest quartile of CD8+ cell density. Consistent trends were observed using allergic asthma (as defined by asthma and allergic rhinitis) for both CD45RO+ and CD8+ subtypes. Conclusion: Although asthma is not associated with overall colorectal cancer risk, immunologic derangement present in asthma patients may influence the recruitment and distribution of CD45RO+ and CD8+ memory T cells to the tumor site. Citation Format: Yu Li, Mingyang Song, Reiko Nishihara, Zhi Rong Qian, Raphaelle Varraso, Kentaro Inamura, Yohei Masugi, Edward L. Giovannucci, Molin Wang, Carlos A. Camargo, Charles S. Fuchs, Andrew T. Chan, Shuji Ogino, Yin Cao. Asthma and risk of colorectal cancer according to tumor immunity and molecular subtypes. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr B11.