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Open AccessArticle

Circadian Gene Polymorphisms Associated with Breast Cancer Susceptibility

1
Department of Molecular Genetics and Epigenetics, Nofer Institute of Occupational Medicine, 91-348 Lodz, Poland
2
Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, 91-348 Lodz, Poland
3
Department of Biological and Environmental Monitoring, Nofer Institute of Occupational Medicine, 91-348 Lodz, Poland
4
Department of Medical Laboratory Diagnostics and Bank of Frozen Tissues and Genetic Specimens, Medical University of Gdansk, 80-211 Gdansk, Poland
5
Biobanking and Biomolecular Resources Research Infrastructure (BBMRI.PL), 80-211 Gdansk, Poland
6
Department of Surgical Oncology, Medical University of Gdansk, 80-214 Gdansk, Poland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(22), 5704; https://doi.org/10.3390/ijms20225704
Received: 21 October 2019 / Revised: 10 November 2019 / Accepted: 11 November 2019 / Published: 14 November 2019
(This article belongs to the Special Issue Crosstalk between Circadian Rhythm and Diseases)
Breast cancer (BC) is a major problem for civilization, manifested by continuously increasing morbidity and mortality among women worldwide. Core circadian genes may play an important role in cancer development and progression. To evaluate the effects of single nucleotide polymorphism (SNP) in circadian genes in BC risk, 16 functional SNPs were genotyped in 321 BC patients and 364 healthy women using the TaqMan fluorescence-labelled probes or High-Resolution Melt Curve technique in the Real-Time PCR system. The selected SNPs were analyzed for the risk of BC, progression, and the influence on gene expression in BC tissue pairs to demonstrate the functionality of genetic variants. The study showed a relationship between an increased BC risk under the dominant genetic model of CRY2 rs10838524, PER2 rs934945, and recessive genetic model of PER1 rs2735611. A protective effect of BMAL1 rs2279287 was observed among carriers with at least one variant allele. Moreover, we found an increased risk of estrogen-/progesterone-positive tumors under the dominant genetic model of PER2 rs934945 and estrogen negative tumors under the variant genotype of CRY2 rs10838524, PER1 rs2735611. We demonstrated significantly altered gene expression of BMAL1, CRY2, PER1, PER2, PER3 according to particular genotypes in the BC tissue pairs. Our findings support the hypothesized role of circadian genes in breast carcinogenesis and indicate probable biomarkers for breast cancer susceptibility. View Full-Text
Keywords: single nucleotide polymorphism; gene expression; circadian rhythm; circadian genes; breast cancer single nucleotide polymorphism; gene expression; circadian rhythm; circadian genes; breast cancer
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Lesicka, M.; Jabłońska, E.; Wieczorek, E.; Pepłońska, B.; Gromadzińska, J.; Seroczyńska, B.; Kalinowski, L.; Skokowski, J.; Reszka, E. Circadian Gene Polymorphisms Associated with Breast Cancer Susceptibility. Int. J. Mol. Sci. 2019, 20, 5704.

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