PT - JOURNAL ARTICLE AU - Shi, Yan AU - Liu, Li AU - Hamada, Tsuyoshi AU - Nowak, Jonathan A. AU - Giannakis, Marios AU - Ma, Yanan AU - Song, Mingyang AU - Nevo, Daniel AU - Kosumi, Keisuke AU - Gu, Mancang AU - Kim, Sun A. AU - Morikawa, Teppei AU - Wu, Kana AU - Sui, Jing AU - Papantoniou, Kyriaki AU - Wang, Molin AU - Chan, Andrew T. AU - Fuchs, Charles S. AU - Meyerhardt, Jeffrey A. AU - Giovannucci, Edward AU - Ogino, Shuji AU - Schernhammer, Eva S. AU - Nishihara, Reiko AU - Zhang, Xuehong TI - Night-Shift Work Duration and Risk of Colorectal Cancer According to <em>IRS1</em> and <em>IRS2</em> Expression AID - 10.1158/1055-9965.EPI-19-0325 DP - 2020 Jan 01 TA - Cancer Epidemiology Biomarkers &amp; Prevention PG - 133--140 VI - 29 IP - 1 4099 - http://cebp.aacrjournals.org/content/29/1/133.short 4100 - http://cebp.aacrjournals.org/content/29/1/133.full SO - Cancer Epidemiol Biomarkers Prev2020 Jan 01; 29 AB - Background: We hypothesized that the risk of colorectal cancer in night-shift workers might be different according to insulin receptor substrate status.Methods: Among 77,470 eligible women having night work assessed in the Nurses' Health Study, we documented a total of 1,397 colorectal cancer 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% confidence intervals (CI) for each colorectal cancer subtype. We measured tumor IRS1 or IRS2 expression by immunohistochemistry (IHC).Results: Compared with women who never worked night shifts, those working ≥15 years night shifts had a marginal trend of increased overall risk of colorectal cancer (Ptrend = 0.06; multivariable HR = 1.20; 95% CI, 0.99–1.45). Longer duration of night-shift work was associated with a higher risk of IRS2-positive tumors (multivariable HR = 2.69; 95% CI, 1.48–4.89; Ptrend = 0.001, ≥15 years night shifts vs. never) but not with IRS2-negative tumors (multivariable HR = 0.90; 95% CI, 0.54–1.51; Ptrend = 0.72; Pheterogeneity for IRS2 = 0.008). Similarly, the corresponding multivariable HRs were 1.81 for IRS1-positive tumors (95% CI, 0.94–3.48; Ptrend = 0.06) and 1.13 for IRS1-negative tumors (95% CI, 0.71–1.80; Ptrend = 0.56; Pheterogeneity for IRS1 = 0.02).Conclusions: Our molecular pathologic 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 colorectal cancer risk in women with abnormal insulin receptor pathways.