Night shift work, chronotype, and prostate cancer risk: Incentives for additional analyses and prevention

Dear Sir, With interest we read the thought-provoking case–control study by Papantoniou et al. into night shift work and prostate cancer risk. We compliment the authors for employing chronotype information in their analyses as a means to capture the endogenous propensity to be awake and asleep. Indeed, whether work is timed during an individual’s endogenous biological night or day must be expected to impact on the resulting stress and strain which has been hypothesized to contribute to the development of cancer. However, we wish to complement (i) that stratifying observed associations of night shift work and prostate cancer by chronotype may mask real effects of “shift work that involves circadian disruption. ” Importantly, (ii) the study results appear to be in line with, albeit limited evidence, that extremes of chronotype may become a promising target for prevention measures. Regarding (i), we explained elsewhere that “it is inappropriate to adjust for chronotype as if it were a bias confounding the relationship between occupational exposure and cancer incidence. ” Thus, we welcome the authors’ approach to consider chronotype as an effect modifier. However, their analysis via stratification and interaction modeling still assumes that all night shifts have the same potency for circadian disruption or chronodisruption (CD) irrespective of the individual chronotype. To overcome this shortcoming, we suggested incorporating “the chronotype information into the exposure assessment in such a way that it takes account of the interaction structure at the design stage already. ” Our suggested definition of a CD metric fills the gap how “shift work that involves circadian disruption” may be defined and used in epidemiological studies, namely “as the split physiological nexus of internal and external times. ” Papantoniou et al. stated that their “data suggest that night shift work that involves circadian disruption may be associated with cancer promotion and therefore decreased survival. ” From our point of view, the authors analysed “night shift work” but not necessarily “night shift work that involves circadian disruption. ” Furthermore, the authors did not examine night work alone but mixed rotating shifts with variable amounts of night shifts. They even included rotating shifts without night work within the reference group which may have further confused findings. For instance, early shifts may be associated with substantial circadian or CD in late chronotypes who, if links between CD and cancer risks were not falsified, may be at increased prostate cancer risks even though not having worked at night. Thus, we suggest focusing on the amount of circadian disruption introduced by all shifts performed in order to measure the effect of appropriately defined “shift work that involves circadian disruption” on prostate cancer risk. Regarding (ii), the authors found that overall risks after long-term night work were higher in evening chronotypes and morning chronotypes. This is in line with what was suggested earlier: “owls” or “larks” may do better during isolated or fixed late day shifts and night shifts or early day shifts, respectively. But both extremes may suffer more than intermediate chronotypes from shift-work rotating through all 24-hr time windows, disallowing to adjust their circadian rhythmicity like people who are neither evening nor morning types. ” Since Papantoniou et al. did not examine night work alone but mixed rotating shifts with variable amounts of night shifts included, their results are compatible with what was “predicted” for extreme chronotypes engaged in rotating shift regimens and cited above. Further empirical evidence supports this rationale: When Hansen and Lassen and Bhatti et al. considered chronobiological propensity or chronotype, respectively, higher cancer risks were observed in extreme chronotypes than in intermediate ones. In addition, Grundy et al. reported circumstantial information on possible selection effects: A Canadian study population, at least with 20 years of shift-work, appeared to consist of less “owls” and “larks” than may have been expected from another study in middle-aged working adults. Demonstration that extreme chronotypes engaged in rotating shift-work were to experience more chronobiological stress and strain than intermediate chronotypes could be relevant to contain hypothesized cancer risks in rotating shift-workers. Indeed, this could imply that we may direct preventative measures to the roughly 25% extreme (comprising 5% early and 20% late chronotypes) chronotypes within the general population. Overall, in terms of methodological rigor, it would be valuable to see the MCC-Spain study additionally analyzed as suggested above with regard to chronotype and “shift work that involved circadian disruption. ” In terms of prevention, limited evidence is compatible with chronobiologically plausible links between certain shift-work schedules with increased cancer risks in certain chronotypes. If this notion is not falsified, possible prevention strategies may target extremes of chronotype to dissuade them from shift-work rotating through all 24-hr time windows. Le tt er to th e E di to r