The impact of genetic variations in retinoid X receptor alpha on the risk and prognosis of HPV-negative oral carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is characterized by a high recurrence rate and poor survival. The retinoid X receptor (RXR) is a nuclear receptor that modulates a variety of biological processes related to cancer, including apoptosis, cellular adhesion, and immune function. A number of cancers exhibit aberrant expression and altered function of the RXR isoform alpha (RXRA), but the polymorphisms in the RXRA gene have not been investigated previously in patients with oral cancer. The current study examined the RXRA rs7864987 and rs3118523 genetic variants, assessed by the real-time PCR Taq-Man method, in 95 HPV-negative OSCC patients and 101 age- and sex-matched healthy controls. Kaplan-Meier analysis revealed that RXRA rs7864987 was significantly associated with worse overall survival and showed a tendency toward lower recurrence-free survival when compared with the wild-type allele carriers (combined TC+TT genotypes) to the mutant genotype CC. RXRA rs7864987, however, did not independently predict overall survival. The C allele of the RXRA rs3118523 genetic variant was associated with a reduced risk of OSCC. Our study indicates that polymorphisms of the RXRA gene may be prognostic and disease-predisposing genetic factors for OSCC. Additionally, RXRA polymorphisms might influence a potential genetic profile-based approach for retinoid therapy in OSCC.