title: Single nucleotide polymorphism of the AXIN2 gene is preferentially associated with human lung cancer risk in a Japanese population.
abstract: The AXIN2 gene, a negative regulator gene of Wnt/beta-catenin signaling, is a putative tumor suppressor gene on human chromosome 17q24. In the genomic locus on which the AXIN2 gene is located, allelic loss and rearrangement were frequently detected in many cancers. An association between human cancer risk and a single nucleotide polymorphism (SNP) at codon 50 of the AXIN2 gene, encoding either proline (CCT) or serine (TCT), remains undefined. We, therefore, investigated the distribution of the SNP at codon 50 in 110 healthy controls and 160 patients with non-small-cell lung cancer, 113 patients with colorectal cancer, and 63 patients with head and neck cancer. We found that the frequency of the homozygous T/T (Ser/Ser) genotype was significantly less in lung cancer patients (5.0%) than in healthy controls (13.6%) (p=0.005). As compared with the C/C (Pro/Pro) genotype of the controls, lung cancer patients with the T/T genotype showed reduced risk of cancer; the adjusted odds ratio (OR) for patients with the homozygous T/T (Ser/Ser) genotype was 0.31 (95% confidence interval (CI), 0.12-0.79). The association was particularly strong in lung cancer patients with lung adenocarcinoma (LAD) (adjusted OR, 0.24; 95% CI, 0.07-0.81), with well-differentiated grade cancer (adjusted OR, 0.12; 95% CI, 0.01-0.99) and with moderately-differentiated grade cancer (adjusted OR, 0.18; 95% CI, 0.04-0.85). These results suggest that the AXIN2 Pro50Ser SNP is associated with development of lung cancer as a protective SNP, while an association between the AXIN2 SNP and risk of colorectal cancer and of head and neck cancer was not observed. This is the first report to show an association between the AXIN2 SNP and lung cancer risk.
authors.affiliation: Department of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kanzaki
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ouchida
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hanafusa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Yano
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Motoi
authors.initials: M
authors.lastname: Aoe
authors.forename: Kazue
authors.initials: K
authors.lastname: Imai
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Shimizu
authors.forename: Kei
authors.initials: K
authors.lastname: Nakachi
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimizu
mesh_terms: D000368:Aged; D060466:Axin Protein; D015179:Colorectal Neoplasms / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011897:Random Allocation; D012307:Risk Factors; D012907:Smoking
chemical_list: C491761:AXIN2 protein, human; D060466:Axin Protein; D003598:Cytoskeletal Proteins