Tagging single nucleotide polymorphisms in MBD4 are associated with risk of lung cancer in a Chinese population.

MBD4 (methyl-CpG binding domain protein 4) was identified as a methyl-CpG binding protein and plays an important role in DNA methylation and carcinogenesis. We hypothesized that genetic variants in MBD4 were associated with lung cancer risk. We selected and genotyped three tagging SNPs (rs2311394, rs140693, and rs2005618) of MBD4 using the illumina SNP genotyping BeadLab platform in a case-control study of 500 incident lung cancer patients and 517 cancer-free controls in a Chinese population. We observed a significantly decreased risk of lung cancer associated with the rs140693 GA genotype (adjusted OR=0.70, 95% CI=0.52-0.93), and the combined rs140693 GA/AA variant genotypes (adjusted OR=0.76, 95% CI=0.58-1.00), compared with the wild-type homozygote rs140693 GG. The reduced lung cancer risk in non-smokers carrying rs140693 GA/AA genotypes was more predominant (adjusted OR=0.56, 95% CI=0.35-0.87). However, there was no statistic evidence of gene-smoking interaction. These findings suggest that genetic variants of MBD4 rs140693 may modulate risk of lung cancer. Further larger case-control and functional studies are needed to validate these findings.

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