NQO1, MPO, and the risk of lung cancer: a HuGE review.
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.
Kiyohara
Chikako
C
Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka, Japan.
Yoshimasu
Kouichi
K
Takayama
Koichi
K
Nakanishi
Yoichi
Y
D020022:Genetic Predisposition to Disease; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D007377:Interleukin-3 / Q000235:genetics*; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D011110:Polymorphism, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D011994:Recombinant Proteins; D012907:Smoking
D007377:Interleukin-3; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C404145:myelopoietin; D016179:Granulocyte Colony-Stimulating Factor; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human