IJC International Journal of Cancer
Authors’ response to Letter to the Editor ~o-Vinyals1,2,3,4, Javier Llorca4,5,6, Marina Pollan4,7,8 and Manolis Kogevinas1,2,4,9 Kyriaki Papantoniou1,2,3,4, Gemma Castan 1
Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain IMIM (Hospital Del Mar Medical Research Institute), Barcelona, Spain 3 Universitat Pompeu Fabra (UPF), Barcelona, Spain 4 blica (CIBERESP), Madrid, Spain CIBER Epidemiologıa Y Salud Pu 5 Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, Santander, Spain 6 IDIVAL, Santander, Spain 7 Environmental and Cancer Epidemiology Area, National Center of Epidemiology, Carlos III Health Institute, Madrid, Spain 8 Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta De Hierro, Madrid, Spain 9 National School of Public Health, Athens, Greece
Letter to the Editor
2
Dear Sir, We thank Dr. Erren and coworkers for their comments.1 We agree with them that individual characteristics such as chronotype, but not only, may modify risks from night work related circadian disruption. This is why we took considerable effort to use a valid instrument evaluating chronotype2 and also why we are examining in a new analysis, genes related to circadian disruption, melatonin signaling and sleep. We do not agree, however, with them in their flat statement that we did not evaluate “night shift work that involves circadian disruption.” “Night shift work that involves circadian disruption” is work that takes place over the biologic night. Given that most people are not extreme chronotypes, night work over the dark period would have caused them considerable amounts of circadian disruption. That is exactly what we tried to capture basing our exposure assessment on time schedules for each job. In addition to the main analysis, we also compared the effect of overnight work to only early morning or only late evening work and results were consistent with the overall effect. We evaluated not only rotating night shifts but also permanent (or “fixed”) night work schedules and we did not find important differences between the two types of night work. Concerning the control group, as already stated in the manuscript, in sensitivity analysis rotating shift workers without night work were excluded and results remained unchanged. Chronotype or circadian/sleep genes may modify the potential effect of night shift on prostate cancer. Some workers, as correctly mentioned by Erren and coworkers may adapt more efficiently than others to a non-normal day–night schedule. Modification, however, implies in most occasions a main effect even in the absence of the effect modifier. In this case, the main effect is circadian disruption due to night shift and the effect modifier is chronotype. Although theoretically possible, there is frankly no evidence that the circadian rhythm of any worker would not be affected by night shift whatever their morningness/eveningness individual characteristics are. In one of the most comprehensive studies,3 we have shown that night shift workers had lower levels and a delay in peak time of 6-sulfatoxymelatonin production over a
C 2015 UICC Int. J. Cancer: 137, 1786–1787 (2015) V
24 hr period from day workers. We also showed that differences were modified by diurnal preference and intensity of light-at-night exposure, but the main differences between night and day workers were present irrespective of the effect modification. Others have also shown similar findings.4 Erren et al.1 may not appreciate well the complications when defining time schedules of workers during a lifetime in population based research. These complex exposure scenarios in epidemiological studies complicate the evaluation of “clean” shift scenarios—such as those described in their letter—as can be done in experimental studies We are actually not even sure whether there is, yet, any primary data supporting the definition suggested by Erren et al. for night work involving circadian disruption according to chronotype. If possible, we would be happy to test this hypothesis within the MCC-Spain study in future analyses. A final consideration refers to the correspondence of acute effects from shift work (e.g., sleepiness) with chronic effects from shift work (e.g., prostate cancer). We know that chronotype is related to the first. Erren is right in mentioning that we may also have differences by chronotype in chronic effects and for this precise reason we did our research. We have, unfortunately, still little evidence on interactions of individual characteristics with shift work conditions and chronic diseases. Whether existing evidence allows us in this phase to target subgroups of researchers for prevention as suggested by Erren et al., is a question; we believe that it is too early to do such recommendations. We hate repeating cliches but in this case “more research is needed. . .”
Authors Contribution All authors participated in writing the letter to the editor, read and approved the final manuscript.
References 1. 2.
Erren TC, Morfeld p, Groß JV. Night shift work, chronotype and prostate cancer risk: incentives for additional analyses and prevention. Int J Cancer, in press. Papantoniou K, Casta~ no-Vinyals G, Espinosa A, et al. Night shift work, chronotype and prostate cancer risk in the MCC-Spain case-control study. Int J Cancer, in press.
Letter to the Editor
3.
DOI: 10.1002/ijc.29523 History: Received 27 Feb 2015; Accepted 3 Mar 2015; Online 21 Mar 2015 Correspondence to: Manolis Kogevinas, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Doctor Aiguader, 88 08003 Barcelona, Spain, E-mail: [email protected]
Letter to the Editor
4.
Papantoniou K, Pozo OJ, Espinosa A, et al. Circadian variation of melatonin, light exposure, and diurnal preference in day and night shift workers of both sexes. Cancer Epidemiol Biomarkers Prev 2014;23:1176–86. Gomez-Acebo I, Dierssen-Sotos T, Papantoniou K, et al. Association between exposure to rotating night shift versus day shift using levels of 6sulfatoxymelatonin and cortisol and other sex hormones in women. Chronobiol Int 2015;32:128–35.
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C 2015 UICC Int. J. Cancer: 137, 1786–1787 (2015) V
Authors’ response to Letter to the Editor ~o-Vinyals1,2,3,4, Javier Llorca4,5,6, Marina Pollan4,7,8 and Manolis Kogevinas1,2,4,9 Kyriaki Papantoniou1,2,3,4, Gemma Castan 1
Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain IMIM (Hospital Del Mar Medical Research Institute), Barcelona, Spain 3 Universitat Pompeu Fabra (UPF), Barcelona, Spain 4 blica (CIBERESP), Madrid, Spain CIBER Epidemiologıa Y Salud Pu 5 Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, Santander, Spain 6 IDIVAL, Santander, Spain 7 Environmental and Cancer Epidemiology Area, National Center of Epidemiology, Carlos III Health Institute, Madrid, Spain 8 Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta De Hierro, Madrid, Spain 9 National School of Public Health, Athens, Greece
Letter to the Editor
2
Dear Sir, We thank Dr. Erren and coworkers for their comments.1 We agree with them that individual characteristics such as chronotype, but not only, may modify risks from night work related circadian disruption. This is why we took considerable effort to use a valid instrument evaluating chronotype2 and also why we are examining in a new analysis, genes related to circadian disruption, melatonin signaling and sleep. We do not agree, however, with them in their flat statement that we did not evaluate “night shift work that involves circadian disruption.” “Night shift work that involves circadian disruption” is work that takes place over the biologic night. Given that most people are not extreme chronotypes, night work over the dark period would have caused them considerable amounts of circadian disruption. That is exactly what we tried to capture basing our exposure assessment on time schedules for each job. In addition to the main analysis, we also compared the effect of overnight work to only early morning or only late evening work and results were consistent with the overall effect. We evaluated not only rotating night shifts but also permanent (or “fixed”) night work schedules and we did not find important differences between the two types of night work. Concerning the control group, as already stated in the manuscript, in sensitivity analysis rotating shift workers without night work were excluded and results remained unchanged. Chronotype or circadian/sleep genes may modify the potential effect of night shift on prostate cancer. Some workers, as correctly mentioned by Erren and coworkers may adapt more efficiently than others to a non-normal day–night schedule. Modification, however, implies in most occasions a main effect even in the absence of the effect modifier. In this case, the main effect is circadian disruption due to night shift and the effect modifier is chronotype. Although theoretically possible, there is frankly no evidence that the circadian rhythm of any worker would not be affected by night shift whatever their morningness/eveningness individual characteristics are. In one of the most comprehensive studies,3 we have shown that night shift workers had lower levels and a delay in peak time of 6-sulfatoxymelatonin production over a
C 2015 UICC Int. J. Cancer: 137, 1786–1787 (2015) V
24 hr period from day workers. We also showed that differences were modified by diurnal preference and intensity of light-at-night exposure, but the main differences between night and day workers were present irrespective of the effect modification. Others have also shown similar findings.4 Erren et al.1 may not appreciate well the complications when defining time schedules of workers during a lifetime in population based research. These complex exposure scenarios in epidemiological studies complicate the evaluation of “clean” shift scenarios—such as those described in their letter—as can be done in experimental studies We are actually not even sure whether there is, yet, any primary data supporting the definition suggested by Erren et al. for night work involving circadian disruption according to chronotype. If possible, we would be happy to test this hypothesis within the MCC-Spain study in future analyses. A final consideration refers to the correspondence of acute effects from shift work (e.g., sleepiness) with chronic effects from shift work (e.g., prostate cancer). We know that chronotype is related to the first. Erren is right in mentioning that we may also have differences by chronotype in chronic effects and for this precise reason we did our research. We have, unfortunately, still little evidence on interactions of individual characteristics with shift work conditions and chronic diseases. Whether existing evidence allows us in this phase to target subgroups of researchers for prevention as suggested by Erren et al., is a question; we believe that it is too early to do such recommendations. We hate repeating cliches but in this case “more research is needed. . .”
Authors Contribution All authors participated in writing the letter to the editor, read and approved the final manuscript.
References 1. 2.
Erren TC, Morfeld p, Groß JV. Night shift work, chronotype and prostate cancer risk: incentives for additional analyses and prevention. Int J Cancer, in press. Papantoniou K, Casta~ no-Vinyals G, Espinosa A, et al. Night shift work, chronotype and prostate cancer risk in the MCC-Spain case-control study. Int J Cancer, in press.
Letter to the Editor
3.
DOI: 10.1002/ijc.29523 History: Received 27 Feb 2015; Accepted 3 Mar 2015; Online 21 Mar 2015 Correspondence to: Manolis Kogevinas, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Doctor Aiguader, 88 08003 Barcelona, Spain, E-mail: [email protected]
Letter to the Editor
4.
Papantoniou K, Pozo OJ, Espinosa A, et al. Circadian variation of melatonin, light exposure, and diurnal preference in day and night shift workers of both sexes. Cancer Epidemiol Biomarkers Prev 2014;23:1176–86. Gomez-Acebo I, Dierssen-Sotos T, Papantoniou K, et al. Association between exposure to rotating night shift versus day shift using levels of 6sulfatoxymelatonin and cortisol and other sex hormones in women. Chronobiol Int 2015;32:128–35.
1787
C 2015 UICC Int. J. Cancer: 137, 1786–1787 (2015) V
