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Titre de la thèse : Perturbation du rythme circadien et risque de cancer de la prostate : rôle du travail de nuit, des gènes circadiens et de leurs interactions

Abstract : In 2007, the International Agency for Research on Cancer (IARC) classified "shift work leading to a disruption of circadian rhythm» as probably carcinogenic to humans (Group 2A) on the basis of sufficient evidence in animals but limited evidence in humans. To date, few studies have focused on the role of night work and clock genes in prostate cancer occurrence. In this context, we studied the role of night work, circadian genes and their interactions in prostate cancer risk, using data from EPICAP, a population-based case-control study, including 819 cases and 879 controls. A standardized questionnaire was used to collect detailed information on both fixed and rotating night work. Biological samples were also collected for DNA genotyping and for prostate cancer-clock genes association study. Overall, we did not find an association between night work and prostate cancer whatever the disease aggressiveness, while we observed an increased risk in men with an evening chronotype. At least 20 years of exposure to fixed night work was associated with aggressive prostate cancer and this was more stricken in combination with long nights (on average more than 10 hours per night shift) or more than 6 consecutive night shifts. We observed a significant association with prostate cancer for the clock genes NPAS2 and PER1, while only RORA was significant for aggressive cancers. We found significant interaction between clock genes and night work in the risk of prostate cancer for RBX1, CRY1, NPAS2 and PRKAG2. Our results provide support for the hypothesis that night work disrupting circadian rhythm could be associated with prostate cancer and they also provide new evidence of a potential link between clock genes variants and prostate cancer. These results may particularly contribute to the identification of new prostate cancer risk factors that could be modifiable and available for prevention. Further studies are warranted to better understand the biological mechanisms involving circadian genes in the development of prostate cancer and their interactions with night work.
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Submitted on : Friday, December 20, 2019 - 1:04:23 AM
Last modification on : Saturday, October 15, 2022 - 3:54:23 AM
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  • HAL Id : tel-02420530, version 1


Meyomo Wendeu-Foyet. Titre de la thèse : Perturbation du rythme circadien et risque de cancer de la prostate : rôle du travail de nuit, des gènes circadiens et de leurs interactions. Santé publique et épidémiologie. Université Paris-Saclay, 2018. Français. ⟨NNT : 2018SACLS591⟩. ⟨tel-02420530⟩



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