Smoking status at diagnosis and colorectal cancer prognosis according to tumor lymphocytic reaction
Fujiyoshi, Kenji; Chen, Yang; Haruki, Koichiro; Ugai, Tomotaka; Kishikawa, Junko; Hamada, Tsuyoshi; Liu, Li; Arima, Kota; Borowsky, Jennifer; Vayrynen, Juha P.; Zhao, Melissa; Lau, Mai Chan; Gu, Simeng; Shi, Shanshan; Akimoto, Naohiko; Twombly, Tyler S.; Drew, David A.; Song, Mingyang; Chan, Andrew T.; Giovannucci, Edward L.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Nishihara, Reiko; Lennerz, Jochen K.; Giannakis, Marios; Nowak, Jonathan A.; Zhang, Xuehong; Wu, Kana; Ogino, Shuji (2020-05-14)
Kenji Fujiyoshi, MD, PhD, Yang Chen, MD, PhD, Koichiro Haruki, MD, PhD, Tomotaka Ugai, MD, PhD, Junko Kishikawa, MD, PhD, Tsuyoshi Hamada, MD, PhD, Li Liu, MD, PhD, Kota Arima, MD, PhD, Jennifer Borowsky, MBChB, Juha P Väyrynen, MD, PhD, Melissa Zhao, MD, Mai Chan Lau, PhD, Simeng Gu, MB, Shanshan Shi, PhD, Naohiko Akimoto, MD, PhD, Tyler S Twombly, BS, David A Drew, PhD, Mingyang Song, MD, ScD, Andrew T Chan, MD, MPH, Edward L Giovannucci, MD, ScD, Jeffrey A Meyerhardt, MD, MPH, Charles S Fuchs, MD, MPH, Reiko Nishihara, PhD, Jochen K Lennerz, MD, PhD, Marios Giannakis, MD, PhD, Jonathan A Nowak, MD, PhD, Xuehong Zhang, MD, ScD, Kana Wu, MD, PhD, Shuji Ogino, MD, PhD, MS, Smoking Status at Diagnosis and Colorectal Cancer Prognosis According to Tumor Lymphocytic Reaction, JNCI Cancer Spectrum, Volume 4, Issue 5, October 2020, pkaa040, https://doi.org/10.1093/jncics/pkaa040
© The Author(s) 2020. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
https://creativecommons.org/licenses/by/4.0/
https://urn.fi/URN:NBN:fi-fe202103106945
Tiivistelmä
Abstract
Background: Smoking has been associated with worse colorectal cancer patient survival and may potentially suppress the immune response in the tumor microenvironment. We hypothesized that the prognostic association of smoking behavior at colorectal cancer diagnosis might differ by lymphocytic reaction patterns in cancer tissue.
Methods: Using 1474 colon and rectal cancer patients within 2 large prospective cohort studies (Nurses’ Health Study and Health Professionals Follow-up Study), we characterized 4 patterns of histopathologic lymphocytic reaction, including tumor-infiltrating lymphocytes (TILs), intratumoral periglandular reaction, peritumoral lymphocytic reaction, and Crohn’s-like lymphoid reaction. Using covariate data of 4420 incident colorectal cancer patients in total, an inverse probability weighted multivariable Cox proportional hazards regression model was conducted to adjust for selection bias due to tissue availability and potential confounders, including tumor differentiation, disease stage, microsatellite instability status, CpG island methylator phenotype, long interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations.
Results: The prognostic association of smoking status at diagnosis differed by TIL status. Compared with never smokers, the multivariable-adjusted colorectal cancer–specific mortality hazard ratio for current smokers was 1.50 (95% confidence interval = 1.10 to 2.06) in tumors with negative or low TIL and 0.43 (95% confidence interval = 0.16 to 1.12) in tumors with intermediate or high TIL (2-sided Pinteraction = 0.009). No statistically significant interactions were observed in the other patterns of lymphocytic reaction.
Conclusions: The association of smoking status at diagnosis with colorectal cancer mortality may be stronger for carcinomas with negative or low TIL, suggesting a potential interplay of smoking and lymphocytic reaction in the colorectal cancer microenvironment.
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