Genetic Variants in <i>MUC4</i> Gene Are Associated with Lung Cancer Risk in a Chinese Population

<div><p>Mucin MUC4, which is encoded by the <i>MUC4</i> gene, plays an important role in epithelial cell proliferation and differentiation. Aberrant <i>MUC4</i> overexpression is associated with invasive tumor proliferation and poor outcome in epithelial cancers. Collectively, the existing evidence suggests that <i>MUC4</i> has tumor-promoter functions. In this study, we performed a case-control study of 1,048 incident lung cancer cases and 1,048 age- and sex frequency-matched cancer-free controls in a Chinese population to investigate the role of <i>MUC4</i> gene polymorphism in lung cancer etiology. We identified nine SNPs that were significantly associated with increased lung cancer risk (<i>P</i> = 0.0425 for rs863582, <i>0.0333</i> for rs842226, <i>0.0294</i> for rs842225, <i>0.0010</i> for rs2550236, <i>0.0149</i> for rs2688515, <i>0.0191</i> for rs 2641773, <i>0.0058</i> for rs3096337, <i>0.0077</i> for rs859769, and <i>0.0059</i> for rs842461 in an additive model). Consistent with these single-locus analysis results, the haplotype analyses revealed an adverse effect of the haplotype “GGC” of rs3096337, rs859769, and rs842461 on lung cancer. Both the haplotype and diplotype “CTGAGC” of rs863582, rs842226, rs2550236, rs842225, and rs2688515 had an adverse effect on lung cancer, which is also consistent with the single-locus analysis. Moreover, we observed statistically significant interactions for rs863582 and rs842461 in heavy smokers. Our results suggest that <i>MUC4</i> gene polymorphisms and their interaction with smoking may contribute to lung cancer etiology. </p> </div

Graphical representation of the SNP locations and LD structure of nine genotyped SNPs of <i>MUC4</i> in 1,048 southern Han Chinese controls.

<p>The exact SNP positions are listed in Table 1. Two haplotype blocks (colored) were defined by the Haploview program using the approach described by Gabriel et al. ^[34] with default settings (the 95% CI for a strong LD was minimal for upper 0.98 and low 0.7, and maximal for a strong recombination of 0.9, and a fraction of strong LD in informative comparisons was at least 0.95). The rs number (top, from right to left) corresponds to the SNP name, and the numbers in squares are D' values (|D'|×100). The measure of LD (D') among all possible pairs of SNPs is shown graphically according to red shading, where white represents very low D', and dark red represents very high D'.</p