Smoking and risk of colorectal cancer sub-classified by tumor-infiltrating T cells

Tsuyoshi Hamada, Jonathan A. Nowak, Yohei Masugi, David A. Drew, Mingyang Song, Yin Cao, Keisuke Kosumi, Kosuke Mima, Tyler S. Twombly, Li Liu, Yan Shi, Annacarolina Da Silva, Mancang Gu, Wanwan Li, Katsuhiko Nosho, Nana Keum, Marios Giannakis, Jeffrey A. Meyerhardt, Kana Wu, Molin WangAndrew T. Chan, Edward L. Giovannucci, Charles S. Fuchs, Reiko Nishihara, Xuehong Zhang, Shuji Ogino

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background Evidence indicates not only carcinogenic effect of cigarette smoking but also its immunosuppressive effect. We hypothesized that the association of smoking with colorectal cancer risk might be stronger for tumors with lower anti-tumor adaptive immune response. Methods During follow-up of 134 981 participants (3 490 851 person-years) in the Nurses' Health Study and Health Professionals Follow-up Study, we documented 729 rectal and colon cancer cases with available data on T-cell densities in tumor microenvironment. Using the duplication-method Cox regression model, we examined a differential association of smoking status with risk of colorectal carcinoma subclassified by densities of CD3 + cells, CD8 + cells, CD45RO (PTPRC) + cells, or FOXP3 + cells. All statistical tests were two-sided. Results The association of smoking status with colorectal cancer risk differed by CD3 + cell density (P heterogeneity =.007). Compared with never smokers, multivariable-adjusted hazard ratios for CD3 + cell-low colorectal cancer were 1.38 (95% confidence interval = 1.09 to 1.75) in former smokers and 1.59 (95% confidence interval = 1.14 to 2.23) in current smokers (P trend =.002, across smoking status categories). In contrast, smoking status was not associated with CD3 + cell-high cancer risk (P trend =.52). This differential association appeared consistent in strata of microsatellite instability, CpG island methylator phenotype, or BRAF mutation status. There was no statistically significant differential association according to densities of CD8 + cells, CD45RO + cells, or FOXP3 + cells (P heterogeneity >.04, with adjusted α of 0.01). Conclusions Colorectal cancer risk increased by smoking was stronger for tumors with lower T-lymphocyte response, suggesting an interplay of smoking and immunity in colorectal carcinogenesis.

Original languageEnglish
Article numberdjy137
JournalJournal of the National Cancer Institute
Volume111
Issue number1
DOIs
Publication statusPublished - 2019 Jan 1
Externally publishedYes

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Colorectal Neoplasms
Smoking
T-Lymphocytes
Neoplasms
Cell Count
Confidence Intervals
Microsatellite Instability
CpG Islands
Tumor Microenvironment
Health
Adaptive Immunity
Immunosuppressive Agents
Rectal Neoplasms
Proportional Hazards Models
Colonic Neoplasms
Immunity
Carcinogenesis
Nurses
Phenotype
Mutation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Smoking and risk of colorectal cancer sub-classified by tumor-infiltrating T cells. / Hamada, Tsuyoshi; Nowak, Jonathan A.; Masugi, Yohei; Drew, David A.; Song, Mingyang; Cao, Yin; Kosumi, Keisuke; Mima, Kosuke; Twombly, Tyler S.; Liu, Li; Shi, Yan; Da Silva, Annacarolina; Gu, Mancang; Li, Wanwan; Nosho, Katsuhiko; Keum, Nana; Giannakis, Marios; Meyerhardt, Jeffrey A.; Wu, Kana; Wang, Molin; Chan, Andrew T.; Giovannucci, Edward L.; Fuchs, Charles S.; Nishihara, Reiko; Zhang, Xuehong; Ogino, Shuji.

In: Journal of the National Cancer Institute, Vol. 111, No. 1, djy137, 01.01.2019.

Research output: Contribution to journalArticle

Hamada, T, Nowak, JA, Masugi, Y, Drew, DA, Song, M, Cao, Y, Kosumi, K, Mima, K, Twombly, TS, Liu, L, Shi, Y, Da Silva, A, Gu, M, Li, W, Nosho, K, Keum, N, Giannakis, M, Meyerhardt, JA, Wu, K, Wang, M, Chan, AT, Giovannucci, EL, Fuchs, CS, Nishihara, R, Zhang, X & Ogino, S 2019, 'Smoking and risk of colorectal cancer sub-classified by tumor-infiltrating T cells', Journal of the National Cancer Institute, vol. 111, no. 1, djy137. https://doi.org/10.1093/jnci/djy137
Hamada, Tsuyoshi ; Nowak, Jonathan A. ; Masugi, Yohei ; Drew, David A. ; Song, Mingyang ; Cao, Yin ; Kosumi, Keisuke ; Mima, Kosuke ; Twombly, Tyler S. ; Liu, Li ; Shi, Yan ; Da Silva, Annacarolina ; Gu, Mancang ; Li, Wanwan ; Nosho, Katsuhiko ; Keum, Nana ; Giannakis, Marios ; Meyerhardt, Jeffrey A. ; Wu, Kana ; Wang, Molin ; Chan, Andrew T. ; Giovannucci, Edward L. ; Fuchs, Charles S. ; Nishihara, Reiko ; Zhang, Xuehong ; Ogino, Shuji. / Smoking and risk of colorectal cancer sub-classified by tumor-infiltrating T cells. In: Journal of the National Cancer Institute. 2019 ; Vol. 111, No. 1.
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abstract = "Background Evidence indicates not only carcinogenic effect of cigarette smoking but also its immunosuppressive effect. We hypothesized that the association of smoking with colorectal cancer risk might be stronger for tumors with lower anti-tumor adaptive immune response. Methods During follow-up of 134 981 participants (3 490 851 person-years) in the Nurses' Health Study and Health Professionals Follow-up Study, we documented 729 rectal and colon cancer cases with available data on T-cell densities in tumor microenvironment. Using the duplication-method Cox regression model, we examined a differential association of smoking status with risk of colorectal carcinoma subclassified by densities of CD3 + cells, CD8 + cells, CD45RO (PTPRC) + cells, or FOXP3 + cells. All statistical tests were two-sided. Results The association of smoking status with colorectal cancer risk differed by CD3 + cell density (P heterogeneity =.007). Compared with never smokers, multivariable-adjusted hazard ratios for CD3 + cell-low colorectal cancer were 1.38 (95{\%} confidence interval = 1.09 to 1.75) in former smokers and 1.59 (95{\%} confidence interval = 1.14 to 2.23) in current smokers (P trend =.002, across smoking status categories). In contrast, smoking status was not associated with CD3 + cell-high cancer risk (P trend =.52). This differential association appeared consistent in strata of microsatellite instability, CpG island methylator phenotype, or BRAF mutation status. There was no statistically significant differential association according to densities of CD8 + cells, CD45RO + cells, or FOXP3 + cells (P heterogeneity >.04, with adjusted α of 0.01). Conclusions Colorectal cancer risk increased by smoking was stronger for tumors with lower T-lymphocyte response, suggesting an interplay of smoking and immunity in colorectal carcinogenesis.",
author = "Tsuyoshi Hamada and Nowak, {Jonathan A.} and Yohei Masugi and Drew, {David A.} and Mingyang Song and Yin Cao and Keisuke Kosumi and Kosuke Mima and Twombly, {Tyler S.} and Li Liu and Yan Shi and {Da Silva}, Annacarolina and Mancang Gu and Wanwan Li and Katsuhiko Nosho and Nana Keum and Marios Giannakis and Meyerhardt, {Jeffrey A.} and Kana Wu and Molin Wang and Chan, {Andrew T.} and Giovannucci, {Edward L.} and Fuchs, {Charles S.} and Reiko Nishihara and Xuehong Zhang and Shuji Ogino",
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T1 - Smoking and risk of colorectal cancer sub-classified by tumor-infiltrating T cells

AU - Hamada, Tsuyoshi

AU - Nowak, Jonathan A.

AU - Masugi, Yohei

AU - Drew, David A.

AU - Song, Mingyang

AU - Cao, Yin

AU - Kosumi, Keisuke

AU - Mima, Kosuke

AU - Twombly, Tyler S.

AU - Liu, Li

AU - Shi, Yan

AU - Da Silva, Annacarolina

AU - Gu, Mancang

AU - Li, Wanwan

AU - Nosho, Katsuhiko

AU - Keum, Nana

AU - Giannakis, Marios

AU - Meyerhardt, Jeffrey A.

AU - Wu, Kana

AU - Wang, Molin

AU - Chan, Andrew T.

AU - Giovannucci, Edward L.

AU - Fuchs, Charles S.

AU - Nishihara, Reiko

AU - Zhang, Xuehong

AU - Ogino, Shuji

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background Evidence indicates not only carcinogenic effect of cigarette smoking but also its immunosuppressive effect. We hypothesized that the association of smoking with colorectal cancer risk might be stronger for tumors with lower anti-tumor adaptive immune response. Methods During follow-up of 134 981 participants (3 490 851 person-years) in the Nurses' Health Study and Health Professionals Follow-up Study, we documented 729 rectal and colon cancer cases with available data on T-cell densities in tumor microenvironment. Using the duplication-method Cox regression model, we examined a differential association of smoking status with risk of colorectal carcinoma subclassified by densities of CD3 + cells, CD8 + cells, CD45RO (PTPRC) + cells, or FOXP3 + cells. All statistical tests were two-sided. Results The association of smoking status with colorectal cancer risk differed by CD3 + cell density (P heterogeneity =.007). Compared with never smokers, multivariable-adjusted hazard ratios for CD3 + cell-low colorectal cancer were 1.38 (95% confidence interval = 1.09 to 1.75) in former smokers and 1.59 (95% confidence interval = 1.14 to 2.23) in current smokers (P trend =.002, across smoking status categories). In contrast, smoking status was not associated with CD3 + cell-high cancer risk (P trend =.52). This differential association appeared consistent in strata of microsatellite instability, CpG island methylator phenotype, or BRAF mutation status. There was no statistically significant differential association according to densities of CD8 + cells, CD45RO + cells, or FOXP3 + cells (P heterogeneity >.04, with adjusted α of 0.01). Conclusions Colorectal cancer risk increased by smoking was stronger for tumors with lower T-lymphocyte response, suggesting an interplay of smoking and immunity in colorectal carcinogenesis.

AB - Background Evidence indicates not only carcinogenic effect of cigarette smoking but also its immunosuppressive effect. We hypothesized that the association of smoking with colorectal cancer risk might be stronger for tumors with lower anti-tumor adaptive immune response. Methods During follow-up of 134 981 participants (3 490 851 person-years) in the Nurses' Health Study and Health Professionals Follow-up Study, we documented 729 rectal and colon cancer cases with available data on T-cell densities in tumor microenvironment. Using the duplication-method Cox regression model, we examined a differential association of smoking status with risk of colorectal carcinoma subclassified by densities of CD3 + cells, CD8 + cells, CD45RO (PTPRC) + cells, or FOXP3 + cells. All statistical tests were two-sided. Results The association of smoking status with colorectal cancer risk differed by CD3 + cell density (P heterogeneity =.007). Compared with never smokers, multivariable-adjusted hazard ratios for CD3 + cell-low colorectal cancer were 1.38 (95% confidence interval = 1.09 to 1.75) in former smokers and 1.59 (95% confidence interval = 1.14 to 2.23) in current smokers (P trend =.002, across smoking status categories). In contrast, smoking status was not associated with CD3 + cell-high cancer risk (P trend =.52). This differential association appeared consistent in strata of microsatellite instability, CpG island methylator phenotype, or BRAF mutation status. There was no statistically significant differential association according to densities of CD8 + cells, CD45RO + cells, or FOXP3 + cells (P heterogeneity >.04, with adjusted α of 0.01). Conclusions Colorectal cancer risk increased by smoking was stronger for tumors with lower T-lymphocyte response, suggesting an interplay of smoking and immunity in colorectal carcinogenesis.

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