A myeloperoxidase polymorphism associated with reduced risk of lung cancer

Matthew B. Schabath; Margaret R. Spitz; Waun K. Hong; George L. Delclos; Wanda F. Reynolds; Gary B. Gunn; Lawrence W. Whitehead; Xifeng Wu

doi:10.1016/S0169-5002(02)00034-X

A myeloperoxidase polymorphism associated with reduced risk of lung cancer

Matthew B. Schabath, Margaret R. Spitz, Waun K. Hong, George L. Delclos, Wanda F. Reynolds, Gary B. Gunn, Lawrence W. Whitehead, Xifeng Wu

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84 Scopus citations

Abstract

Myeloperoxidase (MPO) is a metabolic/oxidative enzyme found in neutrophils and monocytes that contributes to pulmonary carcinogenesis through activation of specific procarcinogens including benzo[a]pyrene intermediates, 4-aminobiphenyl and the arylamines. There is a G→A polymorphism located in the 5′ untranslated region of the MPO gene that may be responsible for reduced transcriptional activity due to the decreased binding affinity for the SP1 transcription factor. Individuals with one or two copies of the A-allele may be afforded protection due to decreased transcriptional activity of MPO and subsequent decreased metabolic activation of procarcinogens. Previous studies have reported a range of protective effects in different ethnic populations. We employed a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) assay to identify the MPO genotypes in 375 lung cancer cases and 378 healthy controls, all of whom were Caucasian. Our results demonstrate a reduced risk of lung cancer when the A-allele genotypes (G/A+A/A) were combined (odds ratio (OR)=0.66; 95% confidence interval (CI) 0.49-0.90). We also noted a protective effect (OR=0.63; 95% CI 0.45-0.87) in ever smokers with the A-allele genotypes which was not evident in never smokers (OR=1.14; 95% CI 0.42-3.11). We observed an incremental decrease in the protective effects as cigarette pack-years increased. Thus, lightest smokers were provided the greatest protection. When the data were stratified by gender, there was a statistically significant reduced risk of lung cancer among men (OR=0.55; 95% CI 0.36-0.84), but not among women (OR=0.81; 95% CI 0.55-1.26) for the A-allele genotypes. Lastly, an age effect was evident only in men but not women. The protective effects of the A-allele genotypes decreased with increasing age. This report provides further support for the hypothesis that a single nucleotide polymorphism in the MPO gene is a protective factor in lung cancer carcinogenesis.

Original language	English (US)
Pages (from-to)	35-40
Number of pages	6
Journal	Lung Cancer
Volume	37
Issue number	1
DOIs	https://doi.org/10.1016/S0169-5002(02)00034-X
State	Published - 2002

Keywords

Genetic susceptibility
Lung cancer
MPO
Molecular epidemiology
Single nucleotide polymorphism

ASJC Scopus subject areas

Oncology
Pulmonary and Respiratory Medicine
Cancer Research

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10.1016/S0169-5002(02)00034-X

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@article{e38a7f8b02e54a28ad1db44dd03dc396,

title = "A myeloperoxidase polymorphism associated with reduced risk of lung cancer",

abstract = "Myeloperoxidase (MPO) is a metabolic/oxidative enzyme found in neutrophils and monocytes that contributes to pulmonary carcinogenesis through activation of specific procarcinogens including benzo[a]pyrene intermediates, 4-aminobiphenyl and the arylamines. There is a G→A polymorphism located in the 5′ untranslated region of the MPO gene that may be responsible for reduced transcriptional activity due to the decreased binding affinity for the SP1 transcription factor. Individuals with one or two copies of the A-allele may be afforded protection due to decreased transcriptional activity of MPO and subsequent decreased metabolic activation of procarcinogens. Previous studies have reported a range of protective effects in different ethnic populations. We employed a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) assay to identify the MPO genotypes in 375 lung cancer cases and 378 healthy controls, all of whom were Caucasian. Our results demonstrate a reduced risk of lung cancer when the A-allele genotypes (G/A+A/A) were combined (odds ratio (OR)=0.66; 95% confidence interval (CI) 0.49-0.90). We also noted a protective effect (OR=0.63; 95% CI 0.45-0.87) in ever smokers with the A-allele genotypes which was not evident in never smokers (OR=1.14; 95% CI 0.42-3.11). We observed an incremental decrease in the protective effects as cigarette pack-years increased. Thus, lightest smokers were provided the greatest protection. When the data were stratified by gender, there was a statistically significant reduced risk of lung cancer among men (OR=0.55; 95% CI 0.36-0.84), but not among women (OR=0.81; 95% CI 0.55-1.26) for the A-allele genotypes. Lastly, an age effect was evident only in men but not women. The protective effects of the A-allele genotypes decreased with increasing age. This report provides further support for the hypothesis that a single nucleotide polymorphism in the MPO gene is a protective factor in lung cancer carcinogenesis.",

keywords = "Genetic susceptibility, Lung cancer, MPO, Molecular epidemiology, Single nucleotide polymorphism",

author = "Schabath, {Matthew B.} and Spitz, {Margaret R.} and Hong, {Waun K.} and Delclos, {George L.} and Reynolds, {Wanda F.} and Gunn, {Gary B.} and Whitehead, {Lawrence W.} and Xifeng Wu",

note = "Funding Information: We gratefully acknowledge laboratory assistance provided by Anna L. Beardsley, field epidemiology assistance provided by Susan Honn, and editorial assistance provided by Dr Maureen E. Goode. This study was supported by grants CA 55769 and CA 74880 from the National Cancer Institute. Matthew B. Schabath was also supported, in part, by a cancer prevention fellowship supported by the National Cancer Institute grant R25 CA57730, Robert M. Chamberlain, Ph.D., Principal Investigator.",

year = "2002",

doi = "10.1016/S0169-5002(02)00034-X",

language = "English (US)",

volume = "37",

pages = "35--40",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "Elsevier Ireland Ltd",

number = "1",

}

TY - JOUR

T1 - A myeloperoxidase polymorphism associated with reduced risk of lung cancer

AU - Schabath, Matthew B.

AU - Spitz, Margaret R.

AU - Hong, Waun K.

AU - Delclos, George L.

AU - Reynolds, Wanda F.

AU - Gunn, Gary B.

AU - Whitehead, Lawrence W.

AU - Wu, Xifeng

N1 - Funding Information: We gratefully acknowledge laboratory assistance provided by Anna L. Beardsley, field epidemiology assistance provided by Susan Honn, and editorial assistance provided by Dr Maureen E. Goode. This study was supported by grants CA 55769 and CA 74880 from the National Cancer Institute. Matthew B. Schabath was also supported, in part, by a cancer prevention fellowship supported by the National Cancer Institute grant R25 CA57730, Robert M. Chamberlain, Ph.D., Principal Investigator.

PY - 2002

Y1 - 2002

N2 - Myeloperoxidase (MPO) is a metabolic/oxidative enzyme found in neutrophils and monocytes that contributes to pulmonary carcinogenesis through activation of specific procarcinogens including benzo[a]pyrene intermediates, 4-aminobiphenyl and the arylamines. There is a G→A polymorphism located in the 5′ untranslated region of the MPO gene that may be responsible for reduced transcriptional activity due to the decreased binding affinity for the SP1 transcription factor. Individuals with one or two copies of the A-allele may be afforded protection due to decreased transcriptional activity of MPO and subsequent decreased metabolic activation of procarcinogens. Previous studies have reported a range of protective effects in different ethnic populations. We employed a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) assay to identify the MPO genotypes in 375 lung cancer cases and 378 healthy controls, all of whom were Caucasian. Our results demonstrate a reduced risk of lung cancer when the A-allele genotypes (G/A+A/A) were combined (odds ratio (OR)=0.66; 95% confidence interval (CI) 0.49-0.90). We also noted a protective effect (OR=0.63; 95% CI 0.45-0.87) in ever smokers with the A-allele genotypes which was not evident in never smokers (OR=1.14; 95% CI 0.42-3.11). We observed an incremental decrease in the protective effects as cigarette pack-years increased. Thus, lightest smokers were provided the greatest protection. When the data were stratified by gender, there was a statistically significant reduced risk of lung cancer among men (OR=0.55; 95% CI 0.36-0.84), but not among women (OR=0.81; 95% CI 0.55-1.26) for the A-allele genotypes. Lastly, an age effect was evident only in men but not women. The protective effects of the A-allele genotypes decreased with increasing age. This report provides further support for the hypothesis that a single nucleotide polymorphism in the MPO gene is a protective factor in lung cancer carcinogenesis.

AB - Myeloperoxidase (MPO) is a metabolic/oxidative enzyme found in neutrophils and monocytes that contributes to pulmonary carcinogenesis through activation of specific procarcinogens including benzo[a]pyrene intermediates, 4-aminobiphenyl and the arylamines. There is a G→A polymorphism located in the 5′ untranslated region of the MPO gene that may be responsible for reduced transcriptional activity due to the decreased binding affinity for the SP1 transcription factor. Individuals with one or two copies of the A-allele may be afforded protection due to decreased transcriptional activity of MPO and subsequent decreased metabolic activation of procarcinogens. Previous studies have reported a range of protective effects in different ethnic populations. We employed a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) assay to identify the MPO genotypes in 375 lung cancer cases and 378 healthy controls, all of whom were Caucasian. Our results demonstrate a reduced risk of lung cancer when the A-allele genotypes (G/A+A/A) were combined (odds ratio (OR)=0.66; 95% confidence interval (CI) 0.49-0.90). We also noted a protective effect (OR=0.63; 95% CI 0.45-0.87) in ever smokers with the A-allele genotypes which was not evident in never smokers (OR=1.14; 95% CI 0.42-3.11). We observed an incremental decrease in the protective effects as cigarette pack-years increased. Thus, lightest smokers were provided the greatest protection. When the data were stratified by gender, there was a statistically significant reduced risk of lung cancer among men (OR=0.55; 95% CI 0.36-0.84), but not among women (OR=0.81; 95% CI 0.55-1.26) for the A-allele genotypes. Lastly, an age effect was evident only in men but not women. The protective effects of the A-allele genotypes decreased with increasing age. This report provides further support for the hypothesis that a single nucleotide polymorphism in the MPO gene is a protective factor in lung cancer carcinogenesis.

KW - Genetic susceptibility

KW - Lung cancer

KW - MPO

KW - Molecular epidemiology

KW - Single nucleotide polymorphism

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U2 - 10.1016/S0169-5002(02)00034-X

DO - 10.1016/S0169-5002(02)00034-X

M3 - Article

C2 - 12057865

AN - SCOPUS:0035985169

SN - 0169-5002

VL - 37

SP - 35

EP - 40

JO - Lung Cancer

JF - Lung Cancer

IS - 1

ER -

A myeloperoxidase polymorphism associated with reduced risk of lung cancer

Abstract

Keywords

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