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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 and , 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 or 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 ( = 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 -positive tumors (multivariable HR = 2.69; 95% CI, 1.48-4.89; = 0.001, ≥15 years night shifts vs. never) but not with -negative tumors (multivariable HR = 0.90; 95% CI, 0.54-1.51; = 0.72; for = 0.008). Similarly, the corresponding multivariable HRs were 1.81 for -positive tumors (95% CI, 0.94-3.48; = 0.06) and 1.13 for -negative tumors (95% CI, 0.71-1.80; = 0.56; for = 0.02).

CONCLUSIONS: Our molecular pathologic epidemiology data suggest a potential role of 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.