Genetic polymorphisms in the polycomb group gene EZH2 and the risk of lung cancer.

INTRODUCTION

Polycomb group (PcG) proteins play essential roles in cellular memory systems and as cell cycle regulators by maintaining homeotic genes in their silenced states. EZH1 and EZH2, the human homologues of the Drosophila gene Enhancer of Zeste (E(z)), are defined as PcG proteins and contain a highly conserved motif, called the SET (Su(var)3-9, Enhancer of Zeste, Trithorax) domain, which is required for histone methyltransferase activity. Increased expression of the transcriptional repressor EZH2 has been reported to be associated with poor prognosis in various malignancies including breast cancer and prostate cancer. Altered expression of EZH2 was also demonstrated in lung cancer, suggesting an involvement in the progression of lung cancer.

METHODS

All 41 polymorphisms in EZH2 were genotyped in 335 patients with lung cancer and 335 age- and gender-matched healthy controls. Finally, 26 polymorphisms were selected for the statistical analysis based on minor allele frequency (>0.05) and linkage disequilibrium.

RESULTS

Two polymorphisms of EZH2, rs6950683 and rs3757441, showed a statistically significant association with reduced risk of lung cancer (adjusted OR [aOR] = 0.71, p = 0.007; aOR = 0.73, p = 0.015, respectively). Two copies of a haplotype (Ht2) of EZH2 also showed a significant association with reduced lung cancer risk (aOR = 0.45, 95% confidence interval = 0.23-0.87).

CONCLUSION

This is the first study to show a significant association between polymorphisms of the PcG gene EZH2 and lung cancer risk. This study suggests a correlation between the genotype variants in EZH2 and reduced lung cancer risk and hence presents a possible marker for lung cancer susceptibility.