Association between CLOCK, PER3 and CCRN4L with non‑small cell lung cancer in Brazilian patients

Circadian rhythms comprise of daily oscillations in a variety of biological processes and are regulated by an endogenous clock. Disruption of these rhythms has been associated with cancer progression, and understanding natural oscillations in cellular growth control, tumor suppression and cancer treatment, may reveal how clock and clock‑controlled genes are regulated in normal physiological functioning. To investigate the association between clock genes and non‑small cell lung cancer (NSCLC), we genotyped three tag SNPs (rs938836, rs17050680, rs3805213) in the Nocturnin gene (CCRN4L), five SNPs (rs228727, rs228644, rs228729, rs707467, rs104620202) in the period 3 (PER3) gene and one SNP (rs6855837) in the CLOCK gene, in 78 Brazilian patients with NSCLC. One tag SNP in CCRN4L (rs3805213) and another tag SNP from PER3 (rs228729) demonstrated a significant correlation with genotype and allele frequency in lung cancer (P=4.4x10‑3 and P=5.7x10‑2; P=0.004 and P=0.02, respectively). The results of our study suggest these polymorphisms in the CCRN4L and PER3 genes may represent a risk factor in the occurrence and development of NSCLC in Brazilian patients.