ABSTRACT
Over the past two decades, several studies have attempted to understand the hypothesis that disrupting the circadian rhythm may promote the development of cancer. Some have suggested that night work and some circadian genes polymorphisms are associated with cancer, including prostate cancer. Our study aims to test the hypothesis that prostate cancer risk among night workers may be modulated by genetic polymorphisms in the circadian pathway genes based on data from the EPICAP study, a population-based case-control study including 1511 men (732 cases/779 controls) with genotyped data. We estimated odds ratio (ORs) and P values of the association between prostate cancer and circadian gene variants using logistic regression models. We tested the interaction between circadian genes variants and night work indicators that were significantly associated with prostate cancer at pathway, gene and SNP levels. Analyses were also stratified by each of these night work indicators and by cancer aggressiveness. The circadian pathway was significantly associated with aggressive prostate cancer among night workers (P = .004), particularly for men who worked at night for <20 years (P = .0002) and those who performed long night shift (>10 hours, P = .001). At the gene level, we observed among night workers significant associations between aggressive prostate cancer and ARNTL, NPAS2 and RORA. At the SNP-level, no significant association was observed. Our findings provide some clues of a potential modulating effect of circadian genes in the relationship between night work and prostate cancer. Further investigation is warranted to confirm these findings and to better elucidate the biological pathways involved.
Subject(s)
ARNTL Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/genetics , Nerve Tissue Proteins/genetics , Nuclear Receptor Subfamily 1, Group F, Member 1/genetics , Polymorphism, Single Nucleotide , Prostatic Neoplasms/pathology , Adult , Aged , Case-Control Studies , Circadian Clocks , Genetic Predisposition to Disease , Genotyping Techniques , Humans , Logistic Models , Male , Middle Aged , Neoplasm Grading , Prostatic Neoplasms/genetics , Shift Work Schedule/adverse effects , Shift Work Schedule/statistics & numerical dataABSTRACT
Circadian rhythms regulate several physiological functions and genes controlling the circadian rhythm were found to regulate cell proliferation, cell cycle and apoptosis. Few studies have investigated the role of those circadian genes in prostate cancer occurrence. We aim to investigate the relationship between circadian genes polymorphisms and prostate cancer risk based on data from the EPICAP study, a population-based case-control study including 1,515 men (732 cases / 783 controls) with genotyped data. Odds Ratios (ORs) for association between prostate cancer and circadian gene variants were estimated for each of the 872 single nucleotide polymorphisms (SNPs) in 31 circadian clock genes. We also used a gene-based and pathway-based approach with a focus on the pathway including 9 core circadian genes. Separate analyses were conducted by prostate cancer aggressiveness. The core-circadian pathway (p = 0.0006) was significantly associated to prostate cancer, for either low (p = 0.002) or high (p = 0.01) grade tumor. At the gene level, we observed significant associations between all prostate cancer and NPAS2 and PER1 after correcting for multiple testing, while only RORA was significant for aggressive tumors. At the SNP-level, no significant association was observed. Our findings provide additional evidence of a potential link between genetic variants in circadian genes and prostate cancer risk. Further investigation is warranted to confirm these findings and to better understand the biological pathways involved.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/genetics , Nerve Tissue Proteins/genetics , Nuclear Receptor Subfamily 1, Group F, Member 1/genetics , Period Circadian Proteins/genetics , Prostatic Neoplasms/pathology , Adult , Aged , Case-Control Studies , Circadian Clocks , Gene Regulatory Networks , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Neoplasm Grading , Odds Ratio , Prostatic Neoplasms/geneticsABSTRACT
Since the publication of the International Agency for Research on Cancer Monograph in 2007 classifying night shift work leading to a disruption of circadian rhythm as probably carcinogenic to humans, there is an increasingly growing interest in understanding how circadian disruption may play a role in cancer development.This systematic review provides a comprehensive update on epidemiologic evidences on circadian disruption and prostate cancer since the last review published in 2012. We identified 12 new studies evaluating the effects of several circadian disruptors such as night shift work, sleep patterns, and circadian genes in prostate cancer risk. In contrast, no new studies have focused on exposure to light at night.Several convincing and biologically plausible hypotheses have been proposed to understand how circadian disruption may be related to cancer. However, the current difficulty of concluding on the role of circadian disruption on prostate cancer risk requires further studies including a better characterization of the different night shift systems, data on sleep patterns and chronotype, measurement of biomarkers, and investigations of polymorphisms in the genes regulating the biological clock. Cancer Epidemiol Biomarkers Prev; 26(7); 985-91. ©2017 AACR.