Interaction between MLL3 genetic polymorphisms, smoking, and alcohol drinking in laryngeal cancer: a case-control study

Abstract

A previous study indicated that MLL3 genetic polymorphisms were associated with human cancer. However, whether MLL3 genetic variants are associated with the risk of laryngeal cancer is not clear. This study investigated the association between MLL3 gene polymorphisms and laryngeal cancer in a Chinese population. Four polymorphisms of the MLL3 gene (rs6943984, rs4725443, rs3800836, rs6464211) were genotyped using the TaqMan method in 592 patients with larynx cancer and 602 age- and sex-matched noncancer controls. We found that rs6943984 and rs4725443 of the MLL3 gene were significantly associated with the risk of larynx cancer after Bonferroni correction. The minor allele A for rs6943984 was associated with increased larynx cancer risk (P < 0.001, OR = 1.960, 95% CI = 1.587-2.420). C allele frequency (0.151) for rs4725443 was significantly higher in the case group than the control group (0.072, P < 0.001). Haplotype analyses showed that haplotypes A-T-A-C and G-T-G-C increased the risk of laryngeal cancer (OR = 2.406, 95% CI: 1.820-3.180, P < 0.001; OR = 1.399, 95% CI: 1.180-1.659, respectively), and haplotypes G-T-A-C and G-T-G-T significantly reduced the risk of laryngeal cancer (OR = 0.332, 95% CI: 0.271-0.408, P < 0.001; OR = 0.742, 95% CI: 0.607-0.908, respectively). We also found that MLL3 rs6943984 and rs4725443 polymorphisms had synergistic effects with smoking or alcohol drinking for the risk of laryngeal cancer. This study indicated that MLL3 genetic polymorphisms and haplotypes were associated with larynx cancer in a Chinese population. There was a mutually synergistic effect between smoking, alcohol drinking, and MLL3 gene polymorphisms for laryngeal cancer.

Keywords: Haplotype; MLL3; laryngeal cancer; polymorphism.

Figure 1

Genetic variations in the human MLL3 gene. Using Haploview 4.2 software and the HapMap phrase II database, we scanned 53‐genotyped single‐nucleotide polymorphisms (SNPs) in Chinese Han. Linkage disequilibrium (LD) blocks across the locus in Chinese Han. LD block derived using the solid spline method in Haploview 4.2. LD values are shown: (A) |D′| × 100; |D′| color scheme: |D′| = 0: white; 0 < |D′| < 1: shades of pink; |D′| = 1: red; (B) r ² × 100; r ² color scheme: r ² = 0: white; 0 < r ² < 1: shades of gray; r ² = 1: black.

Figure 2

Patterns of linkage disequilibrium in the MLL3 gene, with their |D′| (A) and r ² values (B).