Evidence already supports a connection between night shift work and an increased risk of colorectal cancer (CRC), but the mechanism has been difficult to pinpoint. In a study presented at the 2018 American Society of Clinical Oncology Annual Meeting, researchers evaluated the insulin receptor substrate (IRS) 1 and 2 proteins and presented the role they play in the connection of night shift work and CRC.

According to researchers, metabolic disorders can play a part in chronic diseases, including CRC, that are caused by circadian disruption. Two primary mediators that could respond to the metabolic microenvironment are IRS1 and IRS2, and the researchers hypothesized that the risk of CRC in night shift workers might be different, according to IRS expression level.

The study followed 77,470 women who had available night work data, courtesy of the Nurses’ Health Study, for 24 years. A total of 1,397 developed physician-confirmed cases of CRC; of those, 304 and 308 had available data on IRS1 and IRS2, respectively.

Results showed that women working night shifts for 15 years or more had an increased risk of CRC (ptrend = 0.06, multivariable hazard ratio [HR] = 1.20, 95% confidence interval [CI] = 0.99–1.45); the risk of IRS1-positive tumors was higher with a longer night shift duration (multivariable HR = 1.81, 95% CI = 0.94–3.48, ptrend = 0.06).

“Working 15 years or more of rotating night shifts was associated with higher risk of CRC with IRS1-positive or IRS2-positive, but not negative tumors,” the authors said. “These molecular pathologic epidemiology data suggest a potential role of insulin receptor substrate in mediating carcinogenesis induced by night shifts.”