期刊
EUROPEAN RESPIRATORY JOURNAL
卷 35, 期 1, 页码 152-159出版社
EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/09031936.00120808
关键词
Cytochrome P(450); cytochrome P(450) 1A1 gene; haplotype; lung cancer; nonsmall cell lung cancer
资金
- The Prince Charles Hospital Foundation (Brisbane)
- Queensland Smart State (Brisbane) Fellowship
- National Health and Medical Research Council (NHMRC
- Canberra)
- Queensland Cancer Fund (Brisbane)
- NHMRC
Lung cancer remains a leading cause of disease globally, with smoking being the largest single cause. Phase I enzymes, including cytochrome P(450), family 1, subfamily A polypeptide 1 (CYP1A1), are involved in the activation of carcinogens, such as polycyclic aromatic hydrocarbons, to reactive intermediates that are capable of binding covalently to DNA to form DNA adducts, potentially initiating the carcinogenic process. The aim of the present study was to investigate the association of CYP1A1 gene polymorphisms and haplotypes with lung cancer risk. A case-control study was carried out on 1,040 nonsmall cell lung cancer (NSCLC) cases and 784 controls to investigate three CYP1A1 variants, CYP1A1*2A (rs4646903; thymidine to cytosine substitution at nucleotide 3801 (3801T>C)), CYP1A1*2C (rs1048943; 2455A>G; substitution of isoleucine 462 with valine (exon 7)) and CYP1A1*4 (rs1799814; 2453C>A; substitution of threonine 461 with asparagine (exon 7)) using PCR restriction fragment length polymorphism methods. The CYP1A1*2A and CYP1A1*2C variants were significantly over-represented in NSCLC cases compared with controls, whereas the CYP1A1*4 variant was under-represented. CYP1A1 haplotypes (in allelle order CYP1A1*4, CYP1A1*2C, CYP1A1*2A) CGC and CGT were associated with an increased risk of lung cancer, whereas AAT was associated with decreased lung cancer risk in this population. The present study has identified risk haplotypes for CYP1A1 in NSCLC and confirmed that CYP1A1 polymorphisms are a minor risk factor for NSCLC.
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