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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention

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Research Article

Night-shift work duration and risk of colorectal cancer according to IRS1 and IRS2 expression

Yan Shi, Li Liu, Tsuyoshi Hamada, Jonathan A. Nowak, Marios Giannakis, Yanan Ma, Mingyang Song, Daniel Nevo, Keisuke Kosumi, Mancang Gu, Sun A Kim, Teppei Morikawa, Kana Wu, Jing Sui, Kyriaki Papantoniou, Molin Wang, Andrew T. Chan, Charles S. Fuchs, Jeffrey A. Meyerhardt, Edward Giovannucci, Shuji Ogino, Eva S Schernhammer, Reiko Nishihara and Xuehong Zhang
Yan Shi
Department of Medical Oncology, Dana-Farber Cancer Institute
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Li Liu
Dana-Farber Cancer Institute and Harvard Medical School
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Tsuyoshi Hamada
Department of Oncologic Pathology, Dana-Farber Cancer Institute
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Jonathan A. Nowak
Department of Pathology, Brigham and Women's Hospital
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Marios Giannakis
Department of Medical Oncology, Dana-Farber Cancer Institute
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Yanan Ma
Biostatistics and Epidemiology, China Medical University
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Mingyang Song
Massachusetts General Hospital
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Daniel Nevo
Statistics and operation research, Tel Aviv University
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Keisuke Kosumi
Department of Oncologic Pathology, Dana-Farber Cancer Institute
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Mancang Gu
Department of Oncologic Pathology, Dana-Farber Cancer Institute
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Sun A Kim
Department of Medical Oncology, Dana-Farber Cancer Institute
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Teppei Morikawa
Department of Medical Oncology, Dana-Farber Cancer Institute
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Kana Wu
Department of Nutrition, Harvard T.H. Chan School of Public Health
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Jing Sui
Brigham and Women's Hospital
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Kyriaki Papantoniou
Centre for Research in Environmental Epidemiology (CREAL), Center for Research in Environmental Epidemiology
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Molin Wang
Harvard School of Public Health
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Andrew T. Chan
Massachusetts General Hospital
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Charles S. Fuchs
Yale Cancer Center, Yale School of Medicine
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Jeffrey A. Meyerhardt
Department of Medical Oncology, Dana-Farber Cancer Institute
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Edward Giovannucci
Department of Nutrition, Harvard T.H. Chan School of Public Health
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Shuji Ogino
Department of Pathology, Brigham and Women's Hospital
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Eva S Schernhammer
Department of Epidemiology, Harvard School of Public Health
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  • ORCID record for Eva S Schernhammer
Reiko Nishihara
Department of Oncologic Pathology, Dana-Farber Cancer Institute
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Xuehong Zhang
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital
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  • For correspondence: xuehong.zhang@channing.harvard.edu
DOI: 10.1158/1055-9965.EPI-19-0325
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Abstract

Background:We hypothesized that the risk of CRC in night-shift workers might be different according to insulin receptor substrates status. Methods:Among 77,470 eligible women having night work assessed in the Nurses' Health Study, we documented a total of 1,397 CRC cases, of which 304 or 308 had available data on IRS1 and IRS2, respectively. We used duplication method Cox proportional hazards regression analysis for competing risks to calculate HRs and 95% CIs for each CRC subtype. We measured tumor IRS1 or IRS2 expression by immunohistochemistry. Results:Compared with women who never worked night-shifts, those working ≥ 15 years night-shifts had a marginal trend of increased overall risk of CRC (Ptrend = 0.06, multivariable HR = 1.20, 95% CI, 0.99 to 1.45). Longer duration of night-shift work was associated with a higher risk of IRS2-positive tumors (multivariable HR = 2.69, 95% CI 1.48 to 4.89, Ptrend = 0.001, ≥ 15 years night-shifts vs. never) but not with IRS2-negative tumors (multivariable HR = 0.90, 95% CI 0.54 to 1.51, Ptrend = 0.72, Pheterogeneity for IRS2 = 0.008). Similarly, the corresponding multivariable HRs were 1.81 for IRS1-positive tumors (95% CI 0.94 to 3.48, Ptrend = 0.06) and 1.13 for IRS1-negative tumors (95% CI 0.71 to 1.80, Ptrend = 0.56, Pheterogeneity for IRS1 = 0.02). Conclusions:Our molecular pathological epidemiology data suggest a potential role of IRS in mediating carcinogenesis induced by night-shift work. Impact:Although these findings need validation, rotating night-shift might increase CRC risk in women with abnormal insulin receptor pathway.

  • Received March 25, 2019.
  • Revision received August 5, 2019.
  • Accepted October 11, 2019.
  • Copyright ©2019, American Association for Cancer Research.

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Published OnlineFirst October 30, 2019
doi: 10.1158/1055-9965.EPI-19-0325

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Night-shift work duration and risk of colorectal cancer according to IRS1 and IRS2 expression
Yan Shi, Li Liu, Tsuyoshi Hamada, Jonathan A. Nowak, Marios Giannakis, Yanan Ma, Mingyang Song, Daniel Nevo, Keisuke Kosumi, Mancang Gu, Sun A Kim, Teppei Morikawa, Kana Wu, Jing Sui, Kyriaki Papantoniou, Molin Wang, Andrew T. Chan, Charles S. Fuchs, Jeffrey A. Meyerhardt, Edward Giovannucci, Shuji Ogino, Eva S Schernhammer, Reiko Nishihara and Xuehong Zhang
Cancer Epidemiol Biomarkers Prev October 30 2019 DOI: 10.1158/1055-9965.EPI-19-0325

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Night-shift work duration and risk of colorectal cancer according to IRS1 and IRS2 expression
Yan Shi, Li Liu, Tsuyoshi Hamada, Jonathan A. Nowak, Marios Giannakis, Yanan Ma, Mingyang Song, Daniel Nevo, Keisuke Kosumi, Mancang Gu, Sun A Kim, Teppei Morikawa, Kana Wu, Jing Sui, Kyriaki Papantoniou, Molin Wang, Andrew T. Chan, Charles S. Fuchs, Jeffrey A. Meyerhardt, Edward Giovannucci, Shuji Ogino, Eva S Schernhammer, Reiko Nishihara and Xuehong Zhang
Cancer Epidemiol Biomarkers Prev October 30 2019 DOI: 10.1158/1055-9965.EPI-19-0325
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