Variants Identified in the HOXC13 and HOXD13 Genes Suggest Association with Cervical Cancer in a Cohort of Mexican Women

Abstract

HOX genes have been associated with carcinogenesis. However, the molecular mechanism by which tumors are generated remains unclear. The HOXC13 and HOXD13 genes are of interest for their involvement in the development of genitourinary structures. The aim of this first study in the Mexican population was to search for and analyze variants in the coding region of the HOXC13 and HOXD13 genes in women with cervical cancer. Samples from Mexican women with cervical cancer and healthy women were sequenced (50/50). Allelic and genotypic frequencies were compared between groups. The functional impact of the proteins was determined with two bioinformatics servers (SIFT and PolyPhen-2), and the oncogenic potential of the identified nonsynonymous variants was determined using the CGI server. We identified five unreported gene variants: c.895C>A p.(Leu299Ile) and c.777C>T p.(Arg259Arg) in the HOXC13 gene and c.128T>A p.(Phe43Tyr), c.204G>A p.(Ala68Ala), and c.267G>A p.(Ser89Ser) in the HOXD13 gene. In this study, we suggest that the non-synonymous variants c.895C>A p.(Leu299Ile) and c.128T>A p.(Phe43Tyr) could represent a risk factor for the development of the disease, although additional studies in larger patient populations and in different ethnic groups are needed in order to support the results observed.