Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2023 Dec;61(6):2348-2362.
doi: 10.1007/s10528-023-10372-2. Epub 2023 Apr 10.

Relationship Between Breast Cancer Risk and Polymorphisms in CLOCK Gene: A Systematic Review and Meta-Analysis

Affiliations
Meta-Analysis

Relationship Between Breast Cancer Risk and Polymorphisms in CLOCK Gene: A Systematic Review and Meta-Analysis

Yi Shi et al. Biochem Genet. 2023 Dec.

Abstract

Previous studies found that the circadian clock gene participated in the genesis and development of breast cancer. However, research findings on the relationship between polymorphisms in the CLOCK gene and breast cancer risk were inconsistent. This study performed a meta-analysis of the association between CLOCK gene polymorphisms and breast cancer risk. PubMed, Cochrane Library, and Embase databases were electronically searched to collect studies on the association between CLOCK gene polymorphisms and breast cancer risk from inception to February 14, 2022. The quality of the included literature was assessed using the Newcastle-Ottawa Scale. For statistical analysis, odds ratio (OR) and 95% confidence intervals (CIs) were calculated using STATA 14.0. In addition, publication bias was performed by the funnel diagram and the Harbord's regression test. And sensitivity analysis was assessed by the trim and fill method. A total of 6 eligible studies, including 10,164 subjects (5488 breast cancer cases and 4676 controls), were screened in this meta-analysis. Though we did not find a significant association between the polymorphisms in the overall CLOCK gene with breast cancer risk [OR (95%CI) = 0.98 (0.96, 1.01), P = 0.148], we found that compared with T/T types of rs3749474 in CLOCK, T/C and C/C types of rs3749474 were associated with lower risk of breast cancer [OR (95%CI) = 0.93 (0.88, 0.98), P = 0.003]. The sensitivity analysis confirmed the robustness of the results. The funnel plot showed no significant publication bias. Polymorphisms in the CLOCK gene might be associated with breast cancer risk. More studies are needed to confirm the conclusion.

Keywords: Breast cancer; CLOCK gene; Meta-analysis; Polymorphisms.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart illustrating the article selection process according to the PRISMA guidelines
Fig. 2
Fig. 2
Forest plot of the relationship between polymorphisms in CLOCK gene and breast cancer risk (dominant model)
Fig. 3
Fig. 3
Forest plot of the relationship between polymorphisms in CLOCK gene and breast cancer risk (over-dominant model)
Fig. 4
Fig. 4
Forest plot of the relationship between polymorphisms in CLOCK gene and breast cancer risk (recessive model)
Fig. 5
Fig. 5
Forest plot of the relationship between polymorphisms in rs3749474and breast cancer risk (dominant model)
Fig. 6
Fig. 6
Sensitivity analysis of the relationship between polymorphisms in CLOCK gene and breast cancer risk
Fig. 7
Fig. 7
Cutting and patching method of the relationship between polymorphisms in CLOCK gene and breast cancer risk
Fig. 8
Fig. 8
Funnel Plot for publication bias

Similar articles

Cited by

References

    1. Bass J, Takahashi JS. Circadian integration of metabolism and energetics. Science. 2010;330:1349–1354. doi: 10.1126/science.1195027. - DOI - PMC - PubMed
    1. Benna C, Helfrich-Förster C, Rajendran S, Monticelli H, Pilati P, Nitti D, Mocellin S. Genetic variation of clock genes and cancer risk: a field synopsis and meta-analysis. Oncotarget. 2017;8:23978–23995. doi: 10.18632/oncotarget.15074. - DOI - PMC - PubMed
    1. Camblor Murube M, Borregon-Rivilla E, Colmenarejo G, Aguilar-Aguilar E, Martínez JA, Ramírez De Molina A, Reglero G, Loria-Kohen V. Polymorphism of CLOCK gene rs3749474 as a modulator of the circadian evening carbohydrate intake impact on nutritional status in an adult sample. Nutrients. 2020 doi: 10.3390/nu12041142. - DOI - PMC - PubMed
    1. Çetin İ, Topçul M. Investigation of the effects of the endogenous cannabinoid anandamide on luminal a breast cancer cell line MCF-7. Cell Mol Biol (Noisy-le-grand) 2022;68:129–133. doi: 10.14715/cmb/2022.68.4.16. - DOI - PubMed
    1. Cheng H, Chen L, Fang Z, Wan Q, Du Z, Ma N, Guo G, Lu W. The effect of miR-138 on the proliferation and apoptosis of breast cancer cells through the NF-κB/VEGF signaling pathway. Cell Mol Biol (Noisy-le-grand) 2022;68:132–137. doi: 10.14715/cmb/2022.68.2.19. - DOI - PubMed