期刊
ENDOCRINE-RELATED CANCER
卷 21, 期 4, 页码 629-638出版社
BIOSCIENTIFICA LTD
DOI: 10.1530/ERC-14-0121
关键词
breast cancer; case-control study; circadian rhythm; nightwork
资金
- French National Institute of Cancer (INCa)
- Fondation de France
- French Agency for Environmental and Occupational Health Safety (ANSES - ex-AFSSET)
- French National Research Agency (ANR)
- League against Cancer
- Medical Research Council [MC_UP_0801/1] Funding Source: researchfish
- MRC [MC_UP_0801/1] Funding Source: UKRI
Night shiftwork has been associated with an increased risk of breast cancer pointing to a role of circadian disruption. We investigated the role of circadian clock gene polymorphisms and their interaction with nightwork in breast cancer risk in a population-based case-control study in France including 1126 breast cancer cases and 1174 controls. We estimated breast cancer risk associated with each of the 577 single nucleotide polymorphisms (SNPs) in 23 circadian clock genes. We also used a gene-and pathway-based approach to investigate the overall effect on breast cancer of circadian clock gene variants that might not be detected in analyses based on individual SNPs. Interactions with nightwork were tested at the SNP, gene, and pathway levels. We found that two SNPs in RORA (rs1482057 and rs12914272) were associated with breast cancer in the whole sample and among postmenopausal women. In this subpopulation, we also reported an association with rs11932595 in CLOCK, and with CLOCK, RORA, and NPAS2 in the analyses at the gene level. Breast cancer risk in postmenopausal women was also associated with overall genetic variation in the circadian gene pathway (P=0.04), but this association was not detected in premenopausal women. There was some evidence of an interaction between PER1 and nightwork in breast cancer in the whole sample (P=0.024), although the effect was not statistically significant after correcting for multiple testing (P=0.452). Our results support the hypothesis that circadian clock gene variants modulate breast cancer risk.
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