NQO1, MPO, and the risk of lung cancer

A HuGE review

Chikako Kiyohara, Kouichi Yoshimasu, Koichi Takayama, Yoichi Nakanishi

Research output: Contribution to journalReview article

86 Citations (Scopus)

Abstract

The aim of this study is to summarize the available molecular epidemiologic studies of lung cancer and metabolic genes, such as NAD(P)H quinone reductase 1 (NQO1) and myeloperoxidase (MPO). NQO1 plays a dual role in the detoxification and activation of procarcinogens whereas MPO has Phase I activity by converting lipophilic carcinogens into hydrophilic forms. Variant genotypes of both NQO1 Pro187 Ser and MPO G-463A polymorphisms may be related to low enzyme activity. The Pro/Ser and Ser/Ser genotypes combined of NQO1 was significantly associated with decreased risk of lung cancer in Japanese [random effects odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.56-0.88] among whom the variant allele is common. The variant genotype of MPO was associated with decreased risk of lung cancer among Caucasians (random effects OR = 0.70, 95% CI = 0.47-1.04). Gene-environment interactions in both polymorphisms may be hampered by inaccurate categorization of tobacco exposure. Evidence on gene-gene interactions is extremely limited. As lung cancer is a multifactorial disease, an improved understanding of such interactions may help identify individuals at risk for developing lung cancer. Such a study should include larger sample size and other polymorphisms in the metabolism of tobacco-derived carcinogens and address interactions with smoking status. The effects of polymorphisms are best represented by their haplotypes. In future studies on lung cancer, the development of haplotype-based approaches will facilitate the evaluation of haplotypic effects, either for selected polymorphisms physically close to each other or for multiple genes within the same drug-metabolism pathway.

Original languageEnglish
Pages (from-to)463-478
Number of pages16
JournalGenetics in Medicine
Volume7
Issue number7
DOIs
Publication statusPublished - Sep 1 2005

Fingerprint

Peroxidase
Lung Neoplasms
Genotype
Carcinogens
Haplotypes
Tobacco
Odds Ratio
Confidence Intervals
NAD(P)H Dehydrogenase (Quinone)
Genes
Gene-Environment Interaction
Neoplasm Genes
NAD
Sample Size
Epidemiologic Studies
Smoking
Alleles
Enzymes
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)

Cite this

NQO1, MPO, and the risk of lung cancer : A HuGE review. / Kiyohara, Chikako; Yoshimasu, Kouichi; Takayama, Koichi; Nakanishi, Yoichi.

In: Genetics in Medicine, Vol. 7, No. 7, 01.09.2005, p. 463-478.

Research output: Contribution to journalReview article

Kiyohara, Chikako ; Yoshimasu, Kouichi ; Takayama, Koichi ; Nakanishi, Yoichi. / NQO1, MPO, and the risk of lung cancer : A HuGE review. In: Genetics in Medicine. 2005 ; Vol. 7, No. 7. pp. 463-478.
@article{a2745ad044d84156a13a9edd7db25a46,
title = "NQO1, MPO, and the risk of lung cancer: A HuGE review",
abstract = "The aim of this study is to summarize the available molecular epidemiologic studies of lung cancer and metabolic genes, such as NAD(P)H quinone reductase 1 (NQO1) and myeloperoxidase (MPO). NQO1 plays a dual role in the detoxification and activation of procarcinogens whereas MPO has Phase I activity by converting lipophilic carcinogens into hydrophilic forms. Variant genotypes of both NQO1 Pro187 Ser and MPO G-463A polymorphisms may be related to low enzyme activity. The Pro/Ser and Ser/Ser genotypes combined of NQO1 was significantly associated with decreased risk of lung cancer in Japanese [random effects odds ratio (OR) = 0.70, 95{\%} confidence interval (CI) = 0.56-0.88] among whom the variant allele is common. The variant genotype of MPO was associated with decreased risk of lung cancer among Caucasians (random effects OR = 0.70, 95{\%} CI = 0.47-1.04). Gene-environment interactions in both polymorphisms may be hampered by inaccurate categorization of tobacco exposure. Evidence on gene-gene interactions is extremely limited. As lung cancer is a multifactorial disease, an improved understanding of such interactions may help identify individuals at risk for developing lung cancer. Such a study should include larger sample size and other polymorphisms in the metabolism of tobacco-derived carcinogens and address interactions with smoking status. The effects of polymorphisms are best represented by their haplotypes. In future studies on lung cancer, the development of haplotype-based approaches will facilitate the evaluation of haplotypic effects, either for selected polymorphisms physically close to each other or for multiple genes within the same drug-metabolism pathway.",
author = "Chikako Kiyohara and Kouichi Yoshimasu and Koichi Takayama and Yoichi Nakanishi",
year = "2005",
month = "9",
day = "1",
doi = "10.1097/01.gim.0000177530.55043.c1",
language = "English",
volume = "7",
pages = "463--478",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "Lippincott Williams and Wilkins",
number = "7",

}

TY - JOUR

T1 - NQO1, MPO, and the risk of lung cancer

T2 - A HuGE review

AU - Kiyohara, Chikako

AU - Yoshimasu, Kouichi

AU - Takayama, Koichi

AU - Nakanishi, Yoichi

PY - 2005/9/1

Y1 - 2005/9/1

N2 - The aim of this study is to summarize the available molecular epidemiologic studies of lung cancer and metabolic genes, such as NAD(P)H quinone reductase 1 (NQO1) and myeloperoxidase (MPO). NQO1 plays a dual role in the detoxification and activation of procarcinogens whereas MPO has Phase I activity by converting lipophilic carcinogens into hydrophilic forms. Variant genotypes of both NQO1 Pro187 Ser and MPO G-463A polymorphisms may be related to low enzyme activity. The Pro/Ser and Ser/Ser genotypes combined of NQO1 was significantly associated with decreased risk of lung cancer in Japanese [random effects odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.56-0.88] among whom the variant allele is common. The variant genotype of MPO was associated with decreased risk of lung cancer among Caucasians (random effects OR = 0.70, 95% CI = 0.47-1.04). Gene-environment interactions in both polymorphisms may be hampered by inaccurate categorization of tobacco exposure. Evidence on gene-gene interactions is extremely limited. As lung cancer is a multifactorial disease, an improved understanding of such interactions may help identify individuals at risk for developing lung cancer. Such a study should include larger sample size and other polymorphisms in the metabolism of tobacco-derived carcinogens and address interactions with smoking status. The effects of polymorphisms are best represented by their haplotypes. In future studies on lung cancer, the development of haplotype-based approaches will facilitate the evaluation of haplotypic effects, either for selected polymorphisms physically close to each other or for multiple genes within the same drug-metabolism pathway.

AB - The aim of this study is to summarize the available molecular epidemiologic studies of lung cancer and metabolic genes, such as NAD(P)H quinone reductase 1 (NQO1) and myeloperoxidase (MPO). NQO1 plays a dual role in the detoxification and activation of procarcinogens whereas MPO has Phase I activity by converting lipophilic carcinogens into hydrophilic forms. Variant genotypes of both NQO1 Pro187 Ser and MPO G-463A polymorphisms may be related to low enzyme activity. The Pro/Ser and Ser/Ser genotypes combined of NQO1 was significantly associated with decreased risk of lung cancer in Japanese [random effects odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.56-0.88] among whom the variant allele is common. The variant genotype of MPO was associated with decreased risk of lung cancer among Caucasians (random effects OR = 0.70, 95% CI = 0.47-1.04). Gene-environment interactions in both polymorphisms may be hampered by inaccurate categorization of tobacco exposure. Evidence on gene-gene interactions is extremely limited. As lung cancer is a multifactorial disease, an improved understanding of such interactions may help identify individuals at risk for developing lung cancer. Such a study should include larger sample size and other polymorphisms in the metabolism of tobacco-derived carcinogens and address interactions with smoking status. The effects of polymorphisms are best represented by their haplotypes. In future studies on lung cancer, the development of haplotype-based approaches will facilitate the evaluation of haplotypic effects, either for selected polymorphisms physically close to each other or for multiple genes within the same drug-metabolism pathway.

UR - http://www.scopus.com/inward/record.url?scp=26844484537&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=26844484537&partnerID=8YFLogxK

U2 - 10.1097/01.gim.0000177530.55043.c1

DO - 10.1097/01.gim.0000177530.55043.c1

M3 - Review article

VL - 7

SP - 463

EP - 478

JO - Genetics in Medicine

JF - Genetics in Medicine

SN - 1098-3600

IS - 7

ER -