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

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.