TY - JOUR
T1 - Smoking status at diagnosis and colorectal cancer prognosis according to tumor lymphocytic reaction
AU - Fujiyoshi, Kenji
AU - Chen, Yang
AU - Haruki, Koichiro
AU - Ugai, Tomotaka
AU - Kishikawa, Junko
AU - Hamada, Tsuyoshi
AU - Liu, Li
AU - Arima, Kota
AU - Borowsky, Jennifer
AU - Väyrynen, Juha P.
AU - Zhao, Melissa
AU - Lau, Mai Chan
AU - Gu, Simeng
AU - Shi, Shanshan
AU - Akimoto, Naohiko
AU - Twombly, Tyler S.
AU - Drew, David A.
AU - Song, Mingyang
AU - Chan, Andrew T.
AU - Giovannucci, Edward L.
AU - Meyerhardt, Jeffrey A.
AU - Fuchs, Charles S.
AU - Nishihara, Reiko
AU - Lennerz, Jochen K.
AU - Giannakis, Marios
AU - Nowak, Jonathan A.
AU - Zhang, Xuehong
AU - Wu, Kana
AU - Ogino, Shuji
N1 - Publisher Copyright:
© The Author(s) 2020.
PY - 2021
Y1 - 2021
N2 - 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 = .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.
AB - 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 = .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.
UR - https://www.scopus.com/pages/publications/85100767893
U2 - 10.1093/JNCICS/PKAA040
DO - 10.1093/JNCICS/PKAA040
M3 - Article
AN - SCOPUS:85100767893
SN - 2515-5091
VL - 4
JO - JNCI Cancer Spectrum
JF - JNCI Cancer Spectrum
IS - 5
M1 - pkaa040
ER -