CYP1A1 and GSTM1 polymorphisms in relation to lung cancer risk in Chinese women.
We examined CYP1A1 (I462V) and GSTM1 null polymorphisms in 200 female cases and 144 female controls selected from a population-based case-control study of lung cancer conducted in northeast China, where the rates of lung cancer among Chinese women are especially high. The CYP1A1 codon 462 point mutation in exon 7 (I462V) causes an Ile-Val substitution near the heme binding site. This mutation correlates with inducibility of aryl hydrocarbon hydrolase (AHH) activity, which activates polycyclic aromatic hydrocarbons (PAHs) in tobacco smoke and in indoor air pollution from coal-burning stoves, a risk factor for lung cancer in this study population. We found that the CYP1A1 I462V genotype (combined ile/val and val/val) was significantly associated with lung cancer risk. The odds ratio (OR) was 2.5 (95% confidence interval [CI], 1.55-4.03) after adjustment for significant risk factors such as age, ever smoking status, family history of cancer, and eye irritation when cooking. The association was more pronounced among non-smokers (OR=3.67; 95% CI, 1.85-7.28) than among smokers (OR=1.74, 95% CI, 0.85-3.54). In contrast, we did not find a significant association with the GSTM1 null genotype. In summary, our case-control study of lung cancer among women in northeast China revealed an elevated risk associated with the CYP1A1 I462V genotype, but no interaction with smoking or indoor air pollution was found.
Yang
Xiaohong R
XR
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd, Bethesda MD 20892, USA. royang@mail.nih.gov
Wacholder
Sholom
S
Xu
Zhaoyi
Z
Dean
Michael
M
Clark
Vanessa
V
Gold
Bert
B
Brown
Linda M
LM
Stone
B J
BJ
Fraumeni
Joseph F
JF
Caporaso
Neil E
NE
D016902:Air Pollution, Indoor / Q000009:adverse effects; D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D003296:Cooking; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology* / Q000209:etiology / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase