Abstract
The purpose of this study was to assess the LEPR gene Gln223Arg polymorphism (rs1137101) in oral squamous cell carcinoma (OSCC) and in potentially malignant oral lesions (PMOL) in comparison to normal oral mucosa in a Brazilian population. Smokers (n = 89) were selected from a representative sample of 471 individuals from the general population of Montes Claros, Brazil. Participants were age and gender matched to patients with OSCC (n = 25) and oral epithelial dysplasia (n = 25). We investigated the LEPR Gln223Arg polymorphism (A>G; rs1137101) in these groups. Genotype variants were assessed by RFLP-PCR, using MspI (HPAII) restriction endonuclease. The institutional review board of the Universidade Estadual de Montes Claros approved the study (process number 2667/2011). Written informed consent for this study was obtained from all participants. The GG genotype (Arg223Arg) appears to be the more relevant polymorphic variant in OSCC. It occurred, approximately, twice as frequently in OSCC patients than in the general population. In contrast, the A allele in its homozygosis form (Gln223Gln) is significantly associated with the development of PMOL; 80% of the samples from the PMOL group exhibit AA genotype. Our findings suggest new insights regarding LEPR gene variations in the development of OSCC and PMOL.
Highlights
Leptin (LEP) is a protein of the cytokine family, comprised of 167 amino acids
No associations were observed among controls, potentially malignant oral lesions (PMOL), oral squamous cell carcinoma (OSCC) and clinicopathological variables
Leptin (LEP) is a hormone secreted from adipocytes that plays an important role in energetic metabolism, control of food intake, and obesity through its binding to Leptin receptor protein (LEPR) receptors (Dutta et al 2012)
Summary
Leptin (LEP) is a protein of the cytokine family, comprised of 167 amino acids. It is mainly synthesized in adipose tissue and is related to energy metabolism and body weight through hypothalamic regulation. One recently developed peptide was associated with the inhibition of several Leptin-induced pathway in breast and colorectal cancer, including JAK/STAT3, MAPK/ERK1/2 and PI3K/AKT, cyclin D1, and E-cadherin (Beccari et al 2013). Polymorphisms in the LEP and LEPR genes have been associated with several cancer types, such as colon, prostate, and breast cancers (Ribeiro et al 2004; Okobia et al 2008; Slattery et al 2008). Analysis of LEP polymorphism rs7799039 demonstrated that the A allele was associated with higher expression of the Leptin receptor (Ribeiro et al 2004). Leptin has been reported to interfere with the expression of oncogenic c-myc and antiapoptotic bcl-2, regulate cell turnover and facilitate the progression of cervical cancer (Yuan et al 2013)
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