Revisiting the metallothionein genes polymorphisms and the risk of oral squamous cell carcinoma in a Brazilian population / Revisando los polimorfismos de los genes de metalotioneína y el riesgo de carcinoma oral de células escamosas en una población brasileña

ABSTRACT

Background: Metallothioneins (MTs) gene polymorphisms have been associated with the ability of free radicalscavenging and detoxification of heavy metals leading to cancer development. Our aim was to revisit, in a Brazil-ian population, single-nucleotide polymorphisms (SNPs) of the MT gene family previously associated with oralsquamous cell carcinoma (OSCC).Material and Methods: A case-control investigation with 28 OSCC patients and 45 controls was conducted, usingconventional risk factors (tobacco use and alcohol consumption) as covariates. SNPs genotyping for rs8052334(MT1B), rs964372 (MT1B), and rs1610216 (MT2A) was performed by PCR-RFLP, and SNPs for rs11076161(MT1A) were analyzed by TaqMan assay.Results: The only SNP associated with increased risk for OSCC was the MT-1A AA genotype (OR = 4.7; p = 0.01).We have also evidenced for the first time a significant linkage disequilibrium between the SNPs of MT-2A andMT-1A in this population with the highest frequency (30%) of the unfavorable haplotype G/A/C/T (rs1610216 /rs11076161 / rs964372 / rs8052334) of MT gene polymorphisms (OR = 6.2; p = 0.04). Interestingly, after removingthe effects of conventional risk factors, we have uncovered the significance of the AA genotype of the rs11076161with increased odds of 19-fold higher towards OSCC development.Conclusions: This is the first demonstration that a significant linkage disequilibrium among gene polymor-phisms of the MT family may affect susceptibility to oral cancer, which is conditioned by the G/A/C/T haplotype(rs1610216/rs11076161/rs964372/ rs8052334) and the MT-1A gene polymorphism has a potential clinical utility forthe OSCC risk assessment.(AU)