Single nucleotide polymorphism of the AXIN2 gene is preferentially associated with human lung cancer risk in a Japanese population

Hirotaka Kanzaki, Mamoru Ouchida, Hiroko Hanafusa, Masaaki Yano, Hiromitsu Suzuki, Motoi Aoe, Kazue Imai, Nobuyoshi Shimizu, Kei Nakachi, Kenji Shimizu

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Abstract

The AXIN2 gene, a negative regulator gene of Wnt/β-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.

Original languageEnglish
Pages (from-to)279-284
Number of pages6
JournalInternational Journal of Molecular Medicine
Volume18
Issue number2
Publication statusPublished - Aug 2006

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Single Nucleotide Polymorphism
Lung Neoplasms
Population
Genes
Head and Neck Neoplasms
Odds Ratio
Genotype
Confidence Intervals
Neoplasms
Codon
Colorectal Neoplasms
Catenins
Loss of Heterozygosity
Human Chromosomes
Regulator Genes
Tumor Suppressor Genes
Proline
Non-Small Cell Lung Carcinoma
Serine

Keywords

  • β-catenin
  • AXIN2
  • Cancer-predisposition
  • Non-small-cell lung cancer
  • Single nucleotide polymorphism
  • Wnt signaling pathway

ASJC Scopus subject areas

  • Genetics

Cite this

Single nucleotide polymorphism of the AXIN2 gene is preferentially associated with human lung cancer risk in a Japanese population. / Kanzaki, Hirotaka; Ouchida, Mamoru; Hanafusa, Hiroko; Yano, Masaaki; Suzuki, Hiromitsu; Aoe, Motoi; Imai, Kazue; Shimizu, Nobuyoshi; Nakachi, Kei; Shimizu, Kenji.

In: International Journal of Molecular Medicine, Vol. 18, No. 2, 08.2006, p. 279-284.

Research output: Contribution to journalArticle

Kanzaki, Hirotaka ; Ouchida, Mamoru ; Hanafusa, Hiroko ; Yano, Masaaki ; Suzuki, Hiromitsu ; Aoe, Motoi ; Imai, Kazue ; Shimizu, Nobuyoshi ; Nakachi, Kei ; Shimizu, Kenji. / Single nucleotide polymorphism of the AXIN2 gene is preferentially associated with human lung cancer risk in a Japanese population. In: International Journal of Molecular Medicine. 2006 ; Vol. 18, No. 2. pp. 279-284.
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abstract = "The AXIN2 gene, a negative regulator gene of Wnt/β-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.",
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T1 - Single nucleotide polymorphism of the AXIN2 gene is preferentially associated with human lung cancer risk in a Japanese population

AU - Kanzaki, Hirotaka

AU - Ouchida, Mamoru

AU - Hanafusa, Hiroko

AU - Yano, Masaaki

AU - Suzuki, Hiromitsu

AU - Aoe, Motoi

AU - Imai, Kazue

AU - Shimizu, Nobuyoshi

AU - Nakachi, Kei

AU - Shimizu, Kenji

PY - 2006/8

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N2 - The AXIN2 gene, a negative regulator gene of Wnt/β-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.

AB - The AXIN2 gene, a negative regulator gene of Wnt/β-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.

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