Abstract
The G184C and G134A single nucleotide polymorphisms (SNPs) of the CYP1A1 gene result in Ala62Pro and Gly45Asp substitutions, respectively. Here, we tested whether these SNPs are associated with an alteration in lung cancer incidence. We examined 80 Korean subjects with lung cancer and 240 age- and sex-matched controls. For each subject, the CYP1A1 gene was PCR amplified and sequenced. We observed that the odds ratio (OR) for lung cancer was 3.37 higher in subjects with the G184C polymorphism than in controls (95% confidence interval (CI), 0.89~12.73, P = 0.07). In contrast, the OR for lung cancer was 1.23 in subjects with the G134A polymorphism compared to controls (95% CI, 0.68~2.20, P = 0.49). The G184C polymorphism exacerbated the effects of smoking on lung cancer development. Gene-smoking interaction analyses revealed that past or present smokers with the G184C polymorphism had a higher incidence of lung cancer (OR, 24.72; 95% CI, 4.48~136.31; P < 0.01) than control smokers (OR, 6.65; 95% CI, 2.72~16.28; P < 0.01). However, there was only a slight difference in the ORs for lung cancer between control smokers and smokers with the G134A polymorphism. These findings suggest that the G184C polymorphism, but not the G134A polymorphism, is associated with an increased risk of lung cancer.
Keywords: CYP1A1, Single nucleotide polymorphism, G134A, G184C, Gly45Asp, Ala62Pro, Lung cancer
Abbreviations
- CYP
cytochrome P-450
- CI
confidence interval
- OR
odds ratio
- PCR
polymerase chain reaction
- SNP
single nucleotide polymorphism
- WT
wild-type
References
- Bartsch H, Nair U, Risch A, Rojas M, Wikman H, Alexandrov K. Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco-related cancers. Cancer Epidemiol. Biomarkers Prev. 2000;9:3–28. [PubMed] [Google Scholar]
- Crofts F, Cosma GN, Currie D, Taioli E, Toniolo P, Garte SJ. A novel CYP1A1 gene polymorphism in African-Americans. Carcinogenesis. 1993;14:1729–1731. doi: 10.1093/carcin/14.9.1729. [DOI] [PubMed] [Google Scholar]
- Cascorbi I, Brockmoller J, Roots IA. C4887A polymorphism in exon 7 of human CYP1A1: population frequency, mutation linkages, and impact on lung cancer susceptibility. Cancer Res. 1996;56:4965–4969. [PubMed] [Google Scholar]
- Chevalier D, Allorge D, Lo-Guidice JM, Cauffiez C, Lhermitte M, Lafitte JJ, Broly F. Detection of known and two novel (M331I and R464S) missense mutations in the human CYP1A1 gene in a French Caucasian population. Hum. Mutat. 2001;17:355. [PubMed] [Google Scholar]
- Hayashi S, Watanabe J, Nakachi K, Kawajiri K. Genetic linkage of lung cancer-associated Mspl polymorphisms with amino acid replacement in the heme binding region of the human cytochrome P450IA1 gene. J. Biochem. 1991;110:407–411. doi: 10.1093/oxfordjournals.jbchem.a123594. [DOI] [PubMed] [Google Scholar]
- Hung RJ, Boffetta P, Brockmoller J, Butkiewicz D, Cascorbi I, Clapper ML, Garte S, Haugen A, Hirvonen A, Anttila S, Kalina I, Le Marchand L, London SJ, Rannug A, Romkes M, Salagovic J, Schoket B, Gaspari L, Taioli E. CYP1A1 and GSTM1 genetic polymorphisms and lung cancer risk in Caucasian non-smokers: a pooled analysis. Carcinogenesis. 2003;24:875–882. doi: 10.1093/carcin/bgg026. [DOI] [PubMed] [Google Scholar]
- McManus ME, Burgess WM, Veronese ME, Huggett A, Quattrochi LC, Tukey RH. Metabolism of 2-acetylaminofluorene and benzo(a)pyrene and activation of food-derived heterocyclic amine mutagens by human cytochromes P-450. Cancer Res. 1990;50:3367–3376. [PubMed] [Google Scholar]
- Park DW, Jin B, Jang D, Yang K, Park JD, Lee YS, Ryu DY. Genetic polymorphisms of CYP1A1 in a Korean population. Arch. Toxicol. 2004;78:306–308. doi: 10.1007/s00204-004-0552-5. [DOI] [PubMed] [Google Scholar]
- Spurr NK, Gough AC, Stevenson K, Wolf CR. Msp-1 polymorphism detected with a cDNA probe for the P-450 I family on chromosome 15. Nucleic Acids Res. 1987;15:5901. doi: 10.1093/nar/15.14.5901. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smart J, Daly AK. Variation in induced CYP1A1 levels: relationship to CYP1A1, Ah receptor and GSTM1 polymorphisms. Pharmacogenetics. 2000;10:11–24. doi: 10.1097/00008571-200002000-00003. [DOI] [PubMed] [Google Scholar]
- Saito S, Iida A, Sekine A, Ogawa C, Kawauchi S, Higuchi S, Ohno M, Nakamura Y. 906 variations among 27 genes encoding cytochrome P450 (CYP) enzymes and aldehyde dehydrogenases (ALDHs) in the Japanese population. J. Hum. Genet. 2002;47:419–444. doi: 10.1007/s100380200061. [DOI] [PubMed] [Google Scholar]
- Solus JF, Arietta BJ, Harris JR, Sexton DP, Steward JQ, McMunn C, Ihrie P, Mehall JM, Edwards TL, Dawson EP. Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics. 2004;5:895–931. doi: 10.1517/14622416.5.7.895. [DOI] [PubMed] [Google Scholar]
- Song N, Tan W, Xing D, Lin D. CYP 1A1 polymorphism and risk of lung cancer in relation to tobacco smoking: a case-control study in China. Carcinogenesis. 2001;22:11–16. doi: 10.1093/carcin/22.1.11. [DOI] [PubMed] [Google Scholar]
- Sugimura H, Wakai K, Genka K, Nagura K, Igarashi H, Nagayama K, Ohkawa A, Baba S, Morris BJ, Tsugane S, Ohno Y, Gao C, Li Z, Takezaki T, Tajima K, Iwamasa T. Association of lle462Val (Exon 7) polymorphism of cytochrome P450 IA1 with lung cancer in the Asian population: further evidence from a case-control study in Okinawa. Cancer Epidemiol. Biomarkers Prev. 1998;7:413–417. [PubMed] [Google Scholar]
- Vineis P, Veglia F, Benhamou S, Butkiewicz D, Cascorbi I, Clapper ML, Dolzan V, Haugen A, Hirvonen A, Ingelman-Sundberg M, Kihara M, Kiyohara C, Kremers P, LeMarchand L, Ohshima S, Pastorelli R, Rannug A, Romkes M, Schoket B, Shields P, Strange RC, Stucker I, Sugimura H, Garte S, Gaspari L, Taioli E. CYP1A1 T3801 C polymorphism and lung cancer: a pooled analysis of 2451 cases and 3358 controls. Int. J. Cancer. 2003;104:650–657. doi: 10.1002/ijc.10995. [DOI] [PubMed] [Google Scholar]