Abstract
BRCA1 and BRCA2 genes are involved in DNA double-strand break repair and related to breast cancer. Shift work is associated with biological clock alterations and with a higher risk of breast cancer. The aim of this study was to investigate the variability of expression of BRCA genes through the day in healthy subjects and to measure BRCA expression levels in shift workers. The study was approached in two ways. First, we examined diurnal variation of BRCA1 and BRCA2 genes in lymphocytes of 15 volunteers over a 24-hour period. Second, we measured the expression of these genes in lymphocytes from a group of shift and daytime workers. The change in 24-hour expression levels of BRCA1 and BRCA2 genes was statistically significant, decreasing from the peak at midday to the lowest level at midnight. Lower levels for both genes were found in shift workers compared to daytime workers. Diurnal variability of BRCA1 and BRCA2 expression suggests a relation of DNA double-strand break repair system with biological clock. Lower levels of BRCA1 and BRCA2 found in shift workers may be one of the potential factors related to the higher risk of breast cancer.
Highlights
Increasing evidences have demonstrated diurnal variability and involvement of the biological clock in several DNA repair mechanisms [1,2,3,4,5]
Among all genes involved in DNA repair pathways, Breast Cancer 1 (BRCA1) and Breast Cancer 2 (BRCA2) genes are characterized by a particular association with breast cancer [47]
Considering the reduced amplitude observed for the PER2 gene expression in shift workers after a day off [60] and the correlation that we found between BRCA and PER2 gene expression, we speculate that a reduced amplitude of BRCA1 and BRCA2 gene expression in shift workers is probable
Summary
Increasing evidences have demonstrated diurnal variability and involvement of the biological clock in several DNA repair mechanisms [1,2,3,4,5]. Pigmentosum A) protein, implicated in the DNA nucleotide excision repair (NER) system, showed a circadian oscillation in the brain [6]. The HMGB1 (High mobility group box 1) protein, involved in the DNA mismatch repair (MMR), showed a diurnal oscillation in retina [7]. A diurnal modulation of OGG1 (8-oxoguanine DNA glycosylase), responsible for oxidative DNA damage repair and involved in the BER (Basic Excision Repair) system, was found in human lymphocytes by our research group [8]. Breast Cancer 1 (BRCA1) located on chromosome 17 and Breast Cancer 2 (BRCA2) located on chromosome 13 are tumor-suppressor genes involved in the DNA double-strand breaks (DBS) repair. The DBS repair systems are mainly represented by homologous recombination (HR)
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