Circadian Gene Polymorphisms Associated with Breast Cancer Susceptibility

Abstract

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 <i>CRY2</i> rs10838524, <i>PER2</i> rs934945, and recessive genetic model of <i>PER1</i> rs2735611. A protective effect of <i>BMAL1</i> 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 <i>PER2</i> rs934945 and estrogen negative tumors under the variant genotype of <i>CRY2</i> rs10838524, <i>PER1</i> rs2735611. We demonstrated significantly altered gene expression of <i>BMAL1</i>, <i>CRY2</i>, <i>PER1</i>, <i>PER2</i>, <i>PER3</i> 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.