Nonetheless, in this cohort, the downregulation in the mRNA expression of ABCB1 (p-glycoprotein), ABCC1, ERCC1, p-53, and RFC1 in the COS patients suggests the involvement of unknown biological risk factors of genomic instability such as cancer cell mutations, tumour microenvironment (cell types, signalling molecules, and extracellular matrix), epigenetic changes (DNA methylation and histone modification), dysregulation signalling pathways, immune response, and metabolic changes. This evidence concerns the gene RFC1 and cancer.