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.

• Authors: Chikako Kiyohara, Kouichi Yoshimasu, Koichi Takayama, Yoichi Nakanishi
• Journal: Genetics in medicine : official journal of the American College of Medical Genetics (Genet Med) Vol. 7 Issue 7 Pg. 463-78 (Sep 2005) ISSN: 1098-3600 [Print] United States
• PMID: 16170238 (Publication Type: Journal Article, Meta-Analysis, Review)

Chemical References

• Interleukin-3
• Recombinant Fusion Proteins
• Recombinant Proteins
• myelopoietin
• Granulocyte Colony-Stimulating Factor
• NAD(P)H Dehydrogenase (Quinone)
• NQO1 protein, human

Topics

• Genetic Predisposition to Disease
• Granulocyte Colony-Stimulating Factor (genetics)
• Humans
• Interleukin-3 (genetics)
• Lung Neoplasms (epidemiology, etiology, genetics)
• NAD(P)H Dehydrogenase (Quinone) (genetics)
• Polymorphism, Genetic
• Recombinant Fusion Proteins (genetics)
• Recombinant Proteins
• Smoking