Genetic polymorphism in myeloperoxidase but not GSTM1 is associated with risk of lung squamous cell carcinoma in a Chinese population

Wenfu Lu, Deyin Xing, Jun Qi, Wen Tan, Xiaoping Miao, Dongxin Lin

Research output: Contribution to journalArticle

Abstract

Myeloperoxidase (MPO), an enzyme derived from neutrophils, metabolically activates a wide range of carcinogens, whereas glutathione S-transferase M1 (GSTM1) detoxifies various electrophilic metabolites. A -463G→A polymorphism in the promoter region of the MPO gene diminishes the expression of MPO and has been consistently shown to be associated with reduced risk of lung cancer in different ethnic populations. In our study, we have assessed the role of this polymorphism in lung cancer risk in a Chinese population. Genotypes of MPO and GSTM1 were determined by PCR-SSCP and multiplex PCR in 314 patients with lung cancer and 320 frequency-matched controls. The allele frequency for MPO -463A was found to be 0.155 in controls and 0.114 in cases. Subjects with the MPO -463GG genotype were at an increased risk of squamous cell carcinoma (SCC) of the lung compared to those having at least one -463A variant allele (adjusted odds ratio [OR] 2.35; 95% confidence interval [C1] 1.40-3.94). Stratified analysis suggested an interaction between heavy smoking (≥26 pack-years) and the MPO-463GG genotype. The adjusted OR of lung SCC for those having MPO-463GG genotype and smoked ≥26 pack-years was 20.50 (95% C1 5.58-75.33) compared to 6.22 (95% C1 1.72-22.47) for those smoked ≥26 pack-years but having at least one variant A allele (p = 0.023, test for homogeneity). This effect of the MPO polymorphism was not observed in lung adenocarcinoma. GSTM1 deletion was quite common in both controls (49.4%) and cases (50.3%) but was not associated with risk of lung cancer alone or in combination with the MPO polymorphism. Our results confirm the previous reports showing that the variant A allele of MPO has a protective effect against risk of lung cancer.

Original languageEnglish (US)
Pages (from-to)275-279
Number of pages5
JournalInternational Journal of Cancer
Volume102
Issue number3
DOIs
StatePublished - Nov 20 2002
Externally publishedYes

Fingerprint

Genetic Polymorphisms
Peroxidase
Squamous Cell Carcinoma
Lung
Population
Lung Neoplasms
Genotype
Alleles
glutathione S-transferase M1
Odds Ratio
Single-Stranded Conformational Polymorphism
Multiplex Polymerase Chain Reaction
Genetic Promoter Regions
Gene Frequency
Carcinogens
Neutrophils
Smoking
Confidence Intervals
Gene Expression
Polymerase Chain Reaction

Keywords

  • Genetic polymorphism
  • GSTM1
  • Lung cancer
  • Myeloperoxidase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Genetic polymorphism in myeloperoxidase but not GSTM1 is associated with risk of lung squamous cell carcinoma in a Chinese population. / Lu, Wenfu; Xing, Deyin; Qi, Jun; Tan, Wen; Miao, Xiaoping; Lin, Dongxin.

In: International Journal of Cancer, Vol. 102, No. 3, 20.11.2002, p. 275-279.

Research output: Contribution to journalArticle

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abstract = "Myeloperoxidase (MPO), an enzyme derived from neutrophils, metabolically activates a wide range of carcinogens, whereas glutathione S-transferase M1 (GSTM1) detoxifies various electrophilic metabolites. A -463G→A polymorphism in the promoter region of the MPO gene diminishes the expression of MPO and has been consistently shown to be associated with reduced risk of lung cancer in different ethnic populations. In our study, we have assessed the role of this polymorphism in lung cancer risk in a Chinese population. Genotypes of MPO and GSTM1 were determined by PCR-SSCP and multiplex PCR in 314 patients with lung cancer and 320 frequency-matched controls. The allele frequency for MPO -463A was found to be 0.155 in controls and 0.114 in cases. Subjects with the MPO -463GG genotype were at an increased risk of squamous cell carcinoma (SCC) of the lung compared to those having at least one -463A variant allele (adjusted odds ratio [OR] 2.35; 95{\%} confidence interval [C1] 1.40-3.94). Stratified analysis suggested an interaction between heavy smoking (≥26 pack-years) and the MPO-463GG genotype. The adjusted OR of lung SCC for those having MPO-463GG genotype and smoked ≥26 pack-years was 20.50 (95{\%} C1 5.58-75.33) compared to 6.22 (95{\%} C1 1.72-22.47) for those smoked ≥26 pack-years but having at least one variant A allele (p = 0.023, test for homogeneity). This effect of the MPO polymorphism was not observed in lung adenocarcinoma. GSTM1 deletion was quite common in both controls (49.4{\%}) and cases (50.3{\%}) but was not associated with risk of lung cancer alone or in combination with the MPO polymorphism. Our results confirm the previous reports showing that the variant A allele of MPO has a protective effect against risk of lung cancer.",
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AU - Lin, Dongxin

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AB - Myeloperoxidase (MPO), an enzyme derived from neutrophils, metabolically activates a wide range of carcinogens, whereas glutathione S-transferase M1 (GSTM1) detoxifies various electrophilic metabolites. A -463G→A polymorphism in the promoter region of the MPO gene diminishes the expression of MPO and has been consistently shown to be associated with reduced risk of lung cancer in different ethnic populations. In our study, we have assessed the role of this polymorphism in lung cancer risk in a Chinese population. Genotypes of MPO and GSTM1 were determined by PCR-SSCP and multiplex PCR in 314 patients with lung cancer and 320 frequency-matched controls. The allele frequency for MPO -463A was found to be 0.155 in controls and 0.114 in cases. Subjects with the MPO -463GG genotype were at an increased risk of squamous cell carcinoma (SCC) of the lung compared to those having at least one -463A variant allele (adjusted odds ratio [OR] 2.35; 95% confidence interval [C1] 1.40-3.94). Stratified analysis suggested an interaction between heavy smoking (≥26 pack-years) and the MPO-463GG genotype. The adjusted OR of lung SCC for those having MPO-463GG genotype and smoked ≥26 pack-years was 20.50 (95% C1 5.58-75.33) compared to 6.22 (95% C1 1.72-22.47) for those smoked ≥26 pack-years but having at least one variant A allele (p = 0.023, test for homogeneity). This effect of the MPO polymorphism was not observed in lung adenocarcinoma. GSTM1 deletion was quite common in both controls (49.4%) and cases (50.3%) but was not associated with risk of lung cancer alone or in combination with the MPO polymorphism. Our results confirm the previous reports showing that the variant A allele of MPO has a protective effect against risk of lung cancer.

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