2018 ASCO Annual Meeting!
Session: Gastrointestinal (Colorectal) Cancer
Type: Poster Session
Time: Sunday June 3, 8:00 AM to 11:30 AM
Location: Hall A
Night shift work duration and risk of colorectal cancer according to IRS1 and IRS2 expression.
Gastrointestinal (Colorectal) Cancer
2018 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #64)
J Clin Oncol 36, 2018 (suppl; abstr 3571)
Author(s): Yan Shi, Li Liu, Reiko Nishihara, Tsuyoshi Hamada, Mingyang Song, Daniel Nevo, Keisuke Kosumi, Mancang Gu, Kana Wu, Marios Giannakis, Yanan Ma, Jonathan Nowak, Andrew T. Chan, Charles S. Fuchs, Jeffrey A. Meyerhardt, Edward Giovannucci, Guanghai Dai, Eva S Schernhammer, Shuji Ogino, Xuehong Zhang; Chinese PLA General Hospital, Beijing, China; Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, China; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA; Harvard School of Public Health, Boston, MA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, China; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School,, Boston, MA; Channing Laboratory, Boston, MA; Dana-Farber Cancer Institute, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; Brigham and Women's Hospital, Boston, MA; Massachusetts General Hospital/Harvard Medical School, Boston, MA; Smilow Cancer Hospital, Yale New Haven Health, New Haven, CT; Dana-Farber Cancer Institute/ Partners Cancer Care, Boston, MA; Channing Laboratory, Department of Medicine, Harvard Medical School, Boston, MA; General Hospital of Chinese People's Liberation Army, Beijing, China; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA
Background: Although accumulating evidence supports an association between night shift work and an increased risk of colorectal cancer (CRC), the mechanism remains elusive. Notably, metabolic disorders, including insulin resistance, play an important role in both CRC development and other chronic diseases caused by circadian disruption. IRS1 (insulin receptor substrate 1) and IRS2 are the primary mediators of insulin-dependent mitogenesis and could respond to the metabolic microenvironment. We therefore hypothesized that the risk of CRC in night shift workers might be different according to IRSs expression level. Methods: Among 77,470 eligible women with available night work data in the Nurses’ Health Study, we documented a total of 1,397 physician-confirmed CRCs during 24 years of follow-up, of which 304 and 308 had available data on IRS1 and IRS2, respectively. We used duplication method Cox proportional hazards regression analysis for competing risks data to calculate age-adjusted and multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for each CRC subtype. We measured tumor IRS1 or IRS2 protein expression by immunohistochemistry. Results: Compared with women who never worked night shifts, those working a rotating night shift for 15 years or more had a trend of increased overall risk of CRC [Ptrend= 0.06, multivariable HR = 1.20, 95%CI, 0.99 to 1.45]. For the same comparison, longer of night shift duration was associated with a higher risk of IRS1-positive tumors (multivariable HR = 1.81, 95%CI 0.94 to 3.48, Ptrend= 0.06) but not with IRS1-negative tumors (multivariable HR = 1.13, 95%CI 0.71 to 1.80, Ptrend= 0.56, Pheterogeneity for IRS1 subtypes = 0.02). The corresponding multivariable HRs were 2.69 for IRS2-positive tumors (95%CI 1.48 to 4.89, Ptrend= 0.001) and 0.90 for IRS2-negative tumors (95%CI 0.54 to 1.51, Ptrend= 0.72, Pheterogeneity for IRS2 subtypes = 0.008). Conclusions: Working 15 years or more of rotating night shift was associated with higher risk of CRC with IRS1-positive or IRS2-positive, but not negative tumors. This molecular pathological epidemiology data suggest a potential role of insulin receptor substrate in mediating carcinogenesis induced by night shifts.