Abstract
Metallothioneins are intracellular regulators of many biological mechanisms including differentiation, proliferation, angiogenesis and invasion, which are crucial processes in carcinogenesis. This study examines the association between three single-nucleotide polymorphisms at loci −5 A/G (rs28366003) and −209 A/G (rs1610216) in the core promoter region and at locus +838 C/G (rs10636) in 3′UTR region of the metallothionein 2A (MT2A) gene with squamous cell laryngeal cancer (SCLC) risk, as well as with tumor invasiveness according to tumor front grading (TFG). Genotyping was performed using the polymerase chain reaction–restriction fragment length polymorphism technique in 323 genetically unrelated individuals with SCLC and 418 randomly selected healthy volunteers. Only one SNP (rs28366003) was significantly related to laryngeal cancer in the study population. Compared with homozygous common allele carriers, heterozygous and homozygous for the G variant had significantly increased risk of SCLC [adjusted odds ratio (OR) = 2.90, 95 % confidence interval (CI) 1.53–5.21, p dominant < 0.001]. The A/G allele carriers at rs28366003 MT2A were at higher risk of SCLC development (OR = 2.63, 95 % CI 1.41–2.85, p < 0.001]. There was a significant association between the rs28366003 and stage and TFG classification. Most carriers of minor allele had a higher stage (OR = 2.76, 95 % CI 1.11–7.52, p = 0.03), increased cancer aggressiveness, as defined by a higher total TFG score (>18 points) (OR = 3.76, 95 % CI 1.15–12.56, p = 0.03) and diffuse tumor growth (OR = 5.86, 95 % Cl 0.72–44.79, p = 0.08). The results of this study raise a possibility that a genetic variation of MT2A may be implicated in the etiology of laryngeal cancer in a Polish population.
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Acknowledgments
This work was supported, in part, by grant from the National Science Council, Poland (N403 043 32/2326) and by the statutory fund of the Department of Cytobiochemistry, University of Łódź, Poland (506/811).
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The authors declare to have no conflict of interests.
Ethical statement
The investigations were performed with the approval of the Bioethical Commission of the Medical University of Łódź and the National Science Council, Poland (approval no. RNN/60/13/KE).
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Starska, K., Krześlak, A., Forma, E. et al. Genetic polymorphism of metallothionein 2A and risk of laryngeal cancer in a Polish population. Med Oncol 31, 75 (2014). https://doi.org/10.1007/s12032-014-0075-8
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DOI: https://doi.org/10.1007/s12032-014-0075-8