Lung cancer risk associated with selenium status is modified in smoking individuals by Sep15 polymorphism

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Abstract
Background Selenium (Se) is a trace element suggested to act chemopreventive in lung cancer. The mechanism by which Se suppresses tumour development may be associated with some of the functions of selenoproteins, including 15 kDa selenoprotein (Sep15). This protein exhibits antioxidant properties and thus may be involved in the process of carcinogenesis. Recently, it has been shown that the genetic polymorphism of Sep15, resulting in different response of the protein to Se, is associated with the risk of breast and head and neck cancers. Aim of the study The aim of the study was to investigate the possible association between lung cancer risk and Sep15 polymorphism in combination with Se status in the Polish population. Methods The study concerned 325 cases and 287 controls. All the participants were smokers. Plasma Se concentration was determined using graphite furnace atomic absorption spectrometry, and Sep15 polymorphism (1125 G/A transition within 3′-untranslated region) was detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results The adjusted odds ratios (ORs) for lung cancer cases, compared to individuals with Sep15 wild type variant (GG), were: 0.91 (95% CI: 0.64–1.32) for the heterozygous variant (GA) and 0.80 (95% CI: 0.39–1.65) for the homozygous variant (AA). Although plasma Se concentration was statistically lower in lung cancer cases (49.4 ± 17.4 ng/ml) compared to controls (53.3 ± 14.0 ng/ml, p < 0.002), the analysis of the joint effect of Sep15 polymorphism and Se status for lung cancer development revealed that lung cancer risk differed between the Se15 genotype groups. An increasing Se concentration was associated with a decreased risk in all individuals; however, at Se concentration above 80 ng/ml, the risk started to increase in individuals possessing the Sep15 1125 GG or GA genotype. Conclusions It appears that among smoking individuals, those with the Sep15 1125 AA genotype may benefit most from a higher Se intake, whereas in those with the GG or GA genotype, a higher Se status may increase the risk for lung cancer.