• Altered circadian genes expression in breast cancer tissue according to the clinical characteristics

      Lesicka, Monika; Jabłońska, Ewa; Wieczorek, Edyta; Seroczyńska, Barbara; Siekierzycka, Anna; Skokowski, Jarosław; Kalinowski, Leszek; Wąsowicz, Wojciech; Reszka, Edyta; Nofer Institute of Occupational Medicine (2018)
      Breast cancer has a multifactorial etiology. One of the supposed and novel mechanisms is an alteration of circadian gene expression. Circadian genes play a crucial role in many physiological processes. These processes, such as genomic stability, DNA repair mechanism and apoptosis, are frequently disrupted in breast tumors. To assess the significance of circadian gene expression in breast cancer, we carried out an analysis of CLOCK, BMAL1, NPAS2, PER1, PER2, PER3 and CRY1, CRY2, TIMELESS, CSNK1E expression by the use of the quantitative Real-Time PCR technique in tumor tissue and non-tumor adjacent normal tissue sampled from 107 women with a newly diagnosed disease. The obtained data were compared to the clinical and histopathological features. PER1, PER2, PER3, CRY2 were found to be significantly down-expressed, while CLOCK, TIMELESS were over-expressed in the studied tumor samples compared to the non-tumor samples. Only gene expression of CRY1 was significantly down-regulated with progression according to the TNM classification. We found significantly decreased expression of CRY2, PER1, PER2 genes in the ER/PR negative breast tumors compared to the ER/PR positive tumors. Additionally, expression of CRY2, NPAS2 genes had a decreased level in the poorly differentiated tumors in comparison with the well and moderately differentiated ones. Our results indicate that circadian gene expression is altered in breast cancer tissue, which confirms previous observations from various animal and in vitro studies.
    • Circadian Gene Polymorphisms Associated with Breast Cancer Susceptibility.

      Lesicka, Monika; Jabłońska, Ewa; Wieczorek, Edyta; Pepłońska, Beata; Gromadzińska, Jolanta; Seroczyńska, Barbara; Kalinowski, Leszek; Skokowski, Jarosław; Reszka, Edyta; Nofer Institute of Occupational Medicine (2019-11-14)
      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.