CYP1B1, CYP1A1, MPO, and GSTP1 polymorphisms and lung cancer risk in never-smoking Korean women.
Polymorphisms in metabolic genes encoding phase I and phase II enzymes are thought to modulate the risk of lung cancer via changes in enzymatic activity. Recently, the effect of these metabolic enzymes and their interaction with environmental factors has been studied in both smokers and also never-smokers, since never-smokers are a good model in which to study genetic susceptibility at low-dose carcinogen exposure. Here, we investigated the association of CYP1A1 Ile462Val, CYP1B1 Leu432Val, GSTP1 Ile105Val, MPO G-463A polymorphisms and lung cancer risk in never-smoking Korean women. In this case-control study of 213 lung cancer patients and 213 age-matched healthy controls, we found that carrying one variant allele of the CYP1A1 Ile462Val polymorphism was associated with a significantly decreased risk of lung adenocarcinoma (adjusted odds ratio (OR)=0.63; 95% confidence interval (CI), 0.41-0.99). Furthermore, the combination of risk genotypes of CYP1B1 Leu432Val with CYP1A1 Ile462Val was associated with the risk of lung adenocarcinoma (adjusted OR=2.16; 95% CI, 1.02-4.57) as well as overall lung cancer (adjusted OR=2.23; 95% CI 1.01-4.89). The polymorphisms of GSTP1 Ile105Val and MPO G-463A showed no significant association with lung cancer. Theses results suggest that the CYP1A1 Ile462Val polymorphism is associated with a reduced risk of lung adenocarcinoma in never-smoking Korean women, whereas specific combinations of variant genotypes for metabolic enzymes increase lung cancer risk considerably.
Yoon
Kyong-Ah
KA
Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, South Korea.
Kim
Jin Hee
JH
Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, South Korea.
Gil
Hyea-Jin
HJ
Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, South Korea.
Hwang
Hyukkee
H
Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, South Korea.
Hwangbo
Bin
B
Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, South Korea.
Lee
Jin Soo
JS
Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, South Korea. Electronic address: jslee@ncc.re.kr.
D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008875:Middle Aged; D009195:Peroxidase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012907:Smoking
D003577:Cytochrome P-450 Enzyme System; D009195:Peroxidase; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi