title: Genetic variants in MUC4 gene are associated with lung cancer risk in a Chinese population.
abstract: Mucin MUC4, which is encoded by the MUC4 gene, plays an important role in epithelial cell proliferation and differentiation. Aberrant MUC4 overexpression is associated with invasive tumor proliferation and poor outcome in epithelial cancers. Collectively, the existing evidence suggests that MUC4 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 MUC4 gene polymorphism in lung cancer etiology. We identified nine SNPs that were significantly associated with increased lung cancer risk (P = 0.0425 for rs863582, 0.0333 for rs842226, 0.0294 for rs842225, 0.0010 for rs2550236, 0.0149 for rs2688515, 0.0191 for rs 2641773, 0.0058 for rs3096337, 0.0077 for rs859769, and 0.0059 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 MUC4 gene polymorphisms and their interaction with smoking may contribute to lung cancer etiology.
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Zili
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Jianxing
authors.initials: J
authors.lastname: He
authors.forename: Zeguang
authors.initials: Z
authors.lastname: Zheng
authors.forename: Xiansheng
authors.initials: X
authors.lastname: Zeng
authors.forename: Chenting
authors.initials: C
authors.lastname: Zhang
authors.forename: Jinmei
authors.initials: J
authors.lastname: Ye
authors.forename: Yajie
authors.initials: Y
authors.lastname: Zhang
authors.forename: Nanshan
authors.initials: N
authors.lastname: Zhong
authors.forename: Wenju
authors.initials: W
authors.lastname: Lu
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D055264:Mucin-4 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: C524658:MUC4 protein, human; D055264:Mucin-4