A smoking-related plasma protein score and smoking-related cancer risk and mortality in the Atherosclerosis Risk in Communities study

Meng Ru; Christopher Douville; Aghiles Guenoun; Hana Zahed; Christie M. Ballantyne; Kenneth R. Butler; Josef Coresh; David J. Couper; Panagis Galiatsatos; Marc J. Gunter; Ron C. Hoogeveen; Mattias Johansson; Corinne E. Joshu; P. Martijn Kolijn; Christina M. Lill; Jiayun Lu; Michael T. Marrone; Giovanna Masala; David C. Muller; Anna E. Prizment; Raul Zamora-Ros; Nilanjan Chatterjee; Adrienne Tin; Elizabeth A. Platz

doi:10.1093/jnci/djag004

A smoking-related plasma protein score and smoking-related cancer risk and mortality in the Atherosclerosis Risk in Communities study

Meng Ru
, Christopher Douville
, Aghiles Guenoun
, Hana Zahed
, Christie M. Ballantyne
, Kenneth R. Butler
, Josef Coresh
, David J. Couper
, Panagis Galiatsatos
, Marc J. Gunter
, Ron C. Hoogeveen
, Mattias Johansson
, Corinne E. Joshu
, P. Martijn Kolijn
, Christina M. Lill
, Jiayun Lu
, Michael T. Marrone
, Giovanna Masala
, David C. Muller
, Anna E. Prizment

Raul Zamora-Ros, Nilanjan Chatterjee, Adrienne Tin, Elizabeth A. Platz

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Background: Self-reported smoking may not fully capture individualized risk of smoking-related cancer, but circulating proteins may reflect biological consequences of smoking. Thus, we developed a score based on smoking-related proteins and evaluated its association with smoking-related cancer. Methods: This prospective cohort study included 10 563 participants aged 47-70 years in the Atherosclerosis Risk in Communities study. Plasma proteins were measured using the SomaScan Platform (SomaLogic Operating Co, Inc). The score was constructed from proteins associated with current smoking, pack-years, or recent quitting identified by linear regression and elastic net regression. Cox regression was used to estimate adjusted hazard ratios and 95% confidence intervals (CIs). We confirmed the association in a case-cohort study in the European Prospective Investigation into Cancer and Nutrition. Results: Adjusted hazard ratios comparing score quartiles 4 to 1 for total incidence and mortality of 13 smoking-related cancers were 3.89 (95% CI = 3.06 to 4.96) and 5.73 (95% CI = 4.08 to 8.06) before and 2.28 (95% CI = 1.65 to 3.15) and 2.07 (95% CI = 1.74 to 4.10) after adjusting for self-reported smoking. Adjusted hazard ratios for lung cancer were 12.1 (95% CI = 7.11 to 20.6) and 14.2 (95% CI = 7.58 to 26.8) before and 3.04 (95% CI = 1.59 to 5.81) and 4.12 (95% CI = 1.99 to 8.53) after adjusting. In European Prospective Investigation into Cancer and Nutrition, adjusted hazard ratios for lung cancer were 9.47 (95% CI = 6.82 to 13.15) before and 2.23 (95% CI = 1.48 to 3.35) after adjusting. Conclusion: The smoking-related protein score provided relative risk information for smoking-associated cancers beyond self-reported smoking, which was confirmed in an independent cohort. Such a score may be considered for use in risk stratification for prevention and cancer screening in settings in which detailed smoking history cannot be obtained.

Original language	English (US)
Pages (from-to)	917-925
Number of pages	9
Journal	Journal of the National Cancer Institute
Volume	118
Issue number	5
DOIs	https://doi.org/10.1093/jnci/djag004
State	Published - May 2026

Bibliographical note

Publisher Copyright:
© The Author(s) 2026. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected]. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/pages/standard-publication-reuse-rights)

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SDG 3 Good Health and Well-being

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10.1093/jnci/djag004

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Ru, M., Douville, C., Guenoun, A., Zahed, H., Ballantyne, C. M., Butler, K. R., Coresh, J., Couper, D. J., Galiatsatos, P., Gunter, M. J., Hoogeveen, R. C., Johansson, M., Joshu, C. E., Kolijn, P. M., Lill, C. M., Lu, J., Marrone, M. T., Masala, G., Muller, D. C., ... Platz, E. A. (2026). A smoking-related plasma protein score and smoking-related cancer risk and mortality in the Atherosclerosis Risk in Communities study. Journal of the National Cancer Institute, 118(5), 917-925. https://doi.org/10.1093/jnci/djag004

Ru, M, Douville, C, Guenoun, A, Zahed, H, Ballantyne, CM, Butler, KR, Coresh, J, Couper, DJ, Galiatsatos, P, Gunter, MJ, Hoogeveen, RC, Johansson, M, Joshu, CE, Kolijn, PM, Lill, CM, Lu, J, Marrone, MT, Masala, G, Muller, DC, Prizment, AE, Zamora-Ros, R, Chatterjee, N, Tin, A & Platz, EA 2026, 'A smoking-related plasma protein score and smoking-related cancer risk and mortality in the Atherosclerosis Risk in Communities study', Journal of the National Cancer Institute, vol. 118, no. 5, pp. 917-925. https://doi.org/10.1093/jnci/djag004

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title = "A smoking-related plasma protein score and smoking-related cancer risk and mortality in the Atherosclerosis Risk in Communities study",

abstract = "Background: Self-reported smoking may not fully capture individualized risk of smoking-related cancer, but circulating proteins may reflect biological consequences of smoking. Thus, we developed a score based on smoking-related proteins and evaluated its association with smoking-related cancer. Methods: This prospective cohort study included 10 563 participants aged 47-70 years in the Atherosclerosis Risk in Communities study. Plasma proteins were measured using the SomaScan Platform (SomaLogic Operating Co, Inc). The score was constructed from proteins associated with current smoking, pack-years, or recent quitting identified by linear regression and elastic net regression. Cox regression was used to estimate adjusted hazard ratios and 95\% confidence intervals (CIs). We confirmed the association in a case-cohort study in the European Prospective Investigation into Cancer and Nutrition. Results: Adjusted hazard ratios comparing score quartiles 4 to 1 for total incidence and mortality of 13 smoking-related cancers were 3.89 (95\% CI = 3.06 to 4.96) and 5.73 (95\% CI = 4.08 to 8.06) before and 2.28 (95\% CI = 1.65 to 3.15) and 2.07 (95\% CI = 1.74 to 4.10) after adjusting for self-reported smoking. Adjusted hazard ratios for lung cancer were 12.1 (95\% CI = 7.11 to 20.6) and 14.2 (95\% CI = 7.58 to 26.8) before and 3.04 (95\% CI = 1.59 to 5.81) and 4.12 (95\% CI = 1.99 to 8.53) after adjusting. In European Prospective Investigation into Cancer and Nutrition, adjusted hazard ratios for lung cancer were 9.47 (95\% CI = 6.82 to 13.15) before and 2.23 (95\% CI = 1.48 to 3.35) after adjusting. Conclusion: The smoking-related protein score provided relative risk information for smoking-associated cancers beyond self-reported smoking, which was confirmed in an independent cohort. Such a score may be considered for use in risk stratification for prevention and cancer screening in settings in which detailed smoking history cannot be obtained.",

author = "Meng Ru and Christopher Douville and Aghiles Guenoun and Hana Zahed and Ballantyne, \{Christie M.\} and Butler, \{Kenneth R.\} and Josef Coresh and Couper, \{David J.\} and Panagis Galiatsatos and Gunter, \{Marc J.\} and Hoogeveen, \{Ron C.\} and Mattias Johansson and Joshu, \{Corinne E.\} and Kolijn, \{P. Martijn\} and Lill, \{Christina M.\} and Jiayun Lu and Marrone, \{Michael T.\} and Giovanna Masala and Muller, \{David C.\} and Prizment, \{Anna E.\} and Raul Zamora-Ros and Nilanjan Chatterjee and Adrienne Tin and Platz, \{Elizabeth A.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2026. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site{\textemdash}for further information please contact [email protected]. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/pages/standard-publication-reuse-rights)",

year = "2026",

month = may,

doi = "10.1093/jnci/djag004",

language = "English (US)",

volume = "118",

pages = "917--925",

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TY - JOUR

T1 - A smoking-related plasma protein score and smoking-related cancer risk and mortality in the Atherosclerosis Risk in Communities study

AU - Ru, Meng

AU - Douville, Christopher

AU - Guenoun, Aghiles

AU - Zahed, Hana

AU - Ballantyne, Christie M.

AU - Butler, Kenneth R.

AU - Coresh, Josef

AU - Couper, David J.

AU - Galiatsatos, Panagis

AU - Gunter, Marc J.

AU - Hoogeveen, Ron C.

AU - Johansson, Mattias

AU - Joshu, Corinne E.

AU - Kolijn, P. Martijn

AU - Lill, Christina M.

AU - Lu, Jiayun

AU - Marrone, Michael T.

AU - Masala, Giovanna

AU - Muller, David C.

AU - Prizment, Anna E.

AU - Zamora-Ros, Raul

AU - Chatterjee, Nilanjan

AU - Tin, Adrienne

AU - Platz, Elizabeth A.

N1 - Publisher Copyright: © The Author(s) 2026. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected]. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/pages/standard-publication-reuse-rights)

PY - 2026/5

Y1 - 2026/5

N2 - Background: Self-reported smoking may not fully capture individualized risk of smoking-related cancer, but circulating proteins may reflect biological consequences of smoking. Thus, we developed a score based on smoking-related proteins and evaluated its association with smoking-related cancer. Methods: This prospective cohort study included 10 563 participants aged 47-70 years in the Atherosclerosis Risk in Communities study. Plasma proteins were measured using the SomaScan Platform (SomaLogic Operating Co, Inc). The score was constructed from proteins associated with current smoking, pack-years, or recent quitting identified by linear regression and elastic net regression. Cox regression was used to estimate adjusted hazard ratios and 95% confidence intervals (CIs). We confirmed the association in a case-cohort study in the European Prospective Investigation into Cancer and Nutrition. Results: Adjusted hazard ratios comparing score quartiles 4 to 1 for total incidence and mortality of 13 smoking-related cancers were 3.89 (95% CI = 3.06 to 4.96) and 5.73 (95% CI = 4.08 to 8.06) before and 2.28 (95% CI = 1.65 to 3.15) and 2.07 (95% CI = 1.74 to 4.10) after adjusting for self-reported smoking. Adjusted hazard ratios for lung cancer were 12.1 (95% CI = 7.11 to 20.6) and 14.2 (95% CI = 7.58 to 26.8) before and 3.04 (95% CI = 1.59 to 5.81) and 4.12 (95% CI = 1.99 to 8.53) after adjusting. In European Prospective Investigation into Cancer and Nutrition, adjusted hazard ratios for lung cancer were 9.47 (95% CI = 6.82 to 13.15) before and 2.23 (95% CI = 1.48 to 3.35) after adjusting. Conclusion: The smoking-related protein score provided relative risk information for smoking-associated cancers beyond self-reported smoking, which was confirmed in an independent cohort. Such a score may be considered for use in risk stratification for prevention and cancer screening in settings in which detailed smoking history cannot be obtained.

AB - Background: Self-reported smoking may not fully capture individualized risk of smoking-related cancer, but circulating proteins may reflect biological consequences of smoking. Thus, we developed a score based on smoking-related proteins and evaluated its association with smoking-related cancer. Methods: This prospective cohort study included 10 563 participants aged 47-70 years in the Atherosclerosis Risk in Communities study. Plasma proteins were measured using the SomaScan Platform (SomaLogic Operating Co, Inc). The score was constructed from proteins associated with current smoking, pack-years, or recent quitting identified by linear regression and elastic net regression. Cox regression was used to estimate adjusted hazard ratios and 95% confidence intervals (CIs). We confirmed the association in a case-cohort study in the European Prospective Investigation into Cancer and Nutrition. Results: Adjusted hazard ratios comparing score quartiles 4 to 1 for total incidence and mortality of 13 smoking-related cancers were 3.89 (95% CI = 3.06 to 4.96) and 5.73 (95% CI = 4.08 to 8.06) before and 2.28 (95% CI = 1.65 to 3.15) and 2.07 (95% CI = 1.74 to 4.10) after adjusting for self-reported smoking. Adjusted hazard ratios for lung cancer were 12.1 (95% CI = 7.11 to 20.6) and 14.2 (95% CI = 7.58 to 26.8) before and 3.04 (95% CI = 1.59 to 5.81) and 4.12 (95% CI = 1.99 to 8.53) after adjusting. In European Prospective Investigation into Cancer and Nutrition, adjusted hazard ratios for lung cancer were 9.47 (95% CI = 6.82 to 13.15) before and 2.23 (95% CI = 1.48 to 3.35) after adjusting. Conclusion: The smoking-related protein score provided relative risk information for smoking-associated cancers beyond self-reported smoking, which was confirmed in an independent cohort. Such a score may be considered for use in risk stratification for prevention and cancer screening in settings in which detailed smoking history cannot be obtained.

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DO - 10.1093/jnci/djag004

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EP - 925

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 5

ER -

A smoking-related plasma protein score and smoking-related cancer risk and mortality in the Atherosclerosis Risk in Communities study

Abstract

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