Analysis of Klotho 1 gene variants in not melanocytic skin cancer

Abstract

Aim of the study: The incidence of the vast majority of cancers, including melanoma and not melanocytic skin cancer (NMSC) increases with advancing age. However, the mechanism by which aging influences the risk of developing cancer is not fully understood. Whether this is attributable to declines in immunity or other changes, such as changes in the aging microenvironment, remains unclear. Amongst the many proteins implicated in aging is the protein Klotho. Loss of Klotho function results in the early appearance of several pathologies associated with human aging, downregulation of Klotho was found in several cancers, such as pancreatic cancer, HCC, and other tumors. Downregulation of Klotho resulted in promoted proliferation and reduced apoptosis of cancer cells. At the gene level mRNA expression and Klotho protein production is influenced by the presence of a number of SNPs. In particular, the Klotho rs577912, located in intron 1 of the Klotho gene might affect Klotho function. Cells from subjects who had either AA or AC genotype at rs577912 expressed higher levels of Klotho mRNA compared with subjects CC positive. In this view we are evaluating the role of Klotho rs577912 in not melanocytic skin cancer susceptibility. Methods: A group of 44 individuals diagnosed as affected by not melanocytic skin cancer (including 29 Basal Cell Cancer and 15 Squamous Cell Cancer) and 96 unrelated healthy subjects were typed for Klotho1 rs577912, using KASPar SNP genotyping method. Data were statistically analyzed using dominant, codominant, and recessive models. Results: Frequencies of rs577912 Klotho1 genotypes were not different between patients and controls with the exception of a not significant increased frequency of ancestral cytokine homozygous CC genotype in the patients respect to the controls. Conclusions: these preliminary results seem to suggest that Klotho l rs577912 is not involved in NMSC susceptibility.