Abstract
The cytochrome P450 1A1 gene (CYP1A1), encoding Phase I metabolic enzymes, appeared to be a candidate gene for breast cancer risk. However, studies on the association between polymorphisms in this gene and breast cancer have yielded conflicting results. We performed a meta-analysis to investigate the association with breast cancer of the CYP1A1 polymorphisms T3801C (9,316 cases and 12,714 controls) and A2455G (9,552 cases and 9,320 controls). In the genotype contrast of A2455G, both additive [GG vs AA, P = 0.04, fixed-effects OR 0.72; 95% CI (0.53–0.99), P = 0.95 for heterogeneity] and recessive [GG vs (GA + AA), P = 0.04, fixed-effects OR 0.73; 95% CI (0.53–0.99), P = 0.97 for heterogeneity] models produced significant results in east-Asians. In pre-menopausal women in a worldwide population, significant association between A2455G and breast cancer was also found using both models [additive model: P = 0.02, fixed-effects OR 0.52; 95% CI (0.29–0.92), P = 0.39 for heterogeneity; recessive model: P = 0.02, fixed-effects OR 0.51; 95% CI (0.29–0.90), P = 0.38 for heterogeneity]. Our meta-analysis suggests that an A2455G G/G genotype is associated with a trend of reduced breast cancer risk, both in east-Asian women and in pre-menopausal women worldwide, while the T3801C C allele might not be a risk factor for breast cancer. Larger scale primary studies are required to further evaluate the interaction of CYP1A1 polymorphisms and breast cancer risk in specific populations.
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Ambrosone CB, Freudenheim JL, Graham S, Marshall JR, Vena JE, Brasure JR, Laughlin R, Nemoto T, Michalek AM, Harrington A et al (1995) Cytochrome P4501A1 and glutathione S-transferase (M1) genetic polymorphisms and postmenopausal breast cancer risk. Cancer Res 55:3483–3485
Bailey LR, Roodi N, Verrier CS, Yee CJ, Dupont WD, Parl FF (1998) Breast cancer and CYPIA1, GSTM1, and GSTT1 polymorphisms: evidence of a lack of association in Caucasians and African Americans. Cancer Res 58:65–70
Basham VM, Pharoah PD, Healey CS, Luben RN, Day NE, Easton DF, Ponder BA, Dunning AM (2001) Polymorphisms in CYP1A1 and smoking: no association with breast cancer risk. Carcinogenesis 22:1797–1800
Boyapati SM, Shu XO, Gao YT, Cai Q, Jin F, Zheng W (2005) Polymorphisms in CYP1A1 and breast carcinoma risk in a population-based case-control study of Chinese women. Cancer 103:2228–2235
Cascorbi I, Brockmoller J, Roots I (1996) A C4887A polymorphism in exon 7 of human CYP1A1: population frequency, mutation linkages, and impact on lung cancer susceptibility. Cancer Res 56:4965–4969
Chacko P, Joseph T, Mathew BS, Rajan B, Pillai MR (2005) Role of xenobiotic metabolizing gene polymorphisms in breast cancer susceptibility and treatment outcome. Mutat Res 581:153–163
Cosma G, Crofts F, Taioli E, Toniolo P, Garte S (1993) Relationship between genotype and function of the human CYP1A1 gene. J Toxicol Environ Health 40:309–316
Crofts F, Cosma GN, Currie D, Taioli E, Toniolo P, Garte SJ (1993) A novel CYP1A1 gene polymorphism in African-Americans. Carcinogenesis 14:1729–1731
Cushman M, He HM, Katzenellenbogen JA, Lin CM, Hamel E (1995) Synthesis, antitubulin and antimitotic activity, and cytotoxicity of analogs of 2-methoxyestradiol, an endogenous mammalian metabolite of estradiol that inhibits tubulin polymerization by binding to the colchicine binding site. J Med Chem 38:2041–2049
Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634
Fotsis T, Zhang Y, Pepper MS, Adlercreutz H, Montesano R, Nawroth PP, Schweigerer L (1994) The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth. Nature 368:237–239
Hayashi SI, Watanabe J, Nakachi K, Kawajiri K (1991) PCR detection of an A/G polymorphism within exon 7 of the CYP1A1 gene. Nucleic Acids Res 19:4797
Hefler LA, Tempfer CB, Grimm C, Lebrecht A, Ulbrich E, Heinze G, Leodolter S, Schneeberger C, Mueller MW, Muendlein A, Koelbl H (2004) Estrogen-metabolizing gene polymorphisms in the assessment of breast carcinoma risk and fibroadenoma risk in Caucasian women. Cancer 101:264–269
Huang CS, Chern HD, Chang KJ, Cheng CW, Hsu SM, Shen CY (1999a) Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility. Cancer Res 59:4870–4875
Huang CS, Shen CY, Chang KJ, Hsu SM, Chern HD (1999b) Cytochrome P4501A1 polymorphism as a susceptibility factor for breast cancer in postmenopausal Chinese women in Taiwan. Br J Cancer 80:1838–1843
Kawajiri K, Nakachi K, Imai K, Yoshii A, Shinoda N, Watanabe J (1990) Identification of genetically high risk individuals to lung cancer by DNA polymorphisms of the cytochrome P450IA1 gene. FEBS Lett 263:131–133
Kiyohara C, Hirohata T, Inutsuka S (1996) The relationship between aryl hydrocarbon hydroxylase and polymorphisms of the CYP1A1 gene. Jpn J Cancer Res 87:18–24
Krajinovic M, Ghadirian P, Richer C, Sinnett H, Gandini S, Perret C, Lacroix A, Labuda D, Sinnett D (2001) Genetic susceptibility to breast cancer in French-Canadians: role of carcinogen-metabolizing enzymes and gene–environment interactions. Int J Cancer 92:220–225
Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127:820–826
Le Marchand L, Donlon T, Kolonel LN, Henderson BE, Wilkens LR (2005) Estrogen metabolism-related genes and breast cancer risk: the multiethnic cohort study. Cancer Epidemiol Biomarkers Prev 14:1998–2003
Li Y, Millikan RC, Bell DA, Cui L, Tse CK, Newman B, Conway K (2004) Cigarette smoking, cytochrome P4501A1 polymorphisms, and breast cancer among African-American and white women. Breast Cancer Res 6:R460–473
McManus ME, Burgess WM, Veronese ME, Huggett A, Quattrochi LC, Tukey RH (1990) Metabolism of 2-acetylaminofluorene and benzo(a)pyrene and activation of food-derived heterocyclic amine mutagens by human cytochromes P-450. Cancer Res 50:3367–3376
Miyoshi Y, Takahashi Y, Egawa C, Noguchi S (2002) Breast cancer risk associated with CYP1A1 genetic polymorphisms in Japanese women. Breast J 8:209–215
Nebert DW, Dalton TP, Okey AB, Gonzalez FJ (2004) Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer. J Biol Chem 279:23847–23850
Okobia M, Bunker C, Zmuda J, Kammerer C, Vogel V, Uche E, Anyanwu S, Ezeome E, Ferrell R, Kuller L (2005) Cytochrome P4501A1 genetic polymorphisms and breast cancer risk in Nigerian women. Breast Cancer Res Treat 94:285–293
Petitti DB (1994) Meta-analysis, decision analysis, and cost-effectiveness analysis. Oxford University Press, New York
Rosner B (2000) Fundamentals of biostatistics, 5th edn. Duxbury, Boston
Shen Y, Li DK, Wu J, Zhang Z, Gao E (2006) Joint effects of the CYP1A1 MspI, ERalpha PvuII, and ERalpha XbaI polymorphisms on the risk of breast cancer: results from a population-based case-control study in Shanghai, China. Cancer Epidemiol Biomarkers Prev 15:342–347
Singh V, Rastogi N, Sinha A, Kumar A, Mathur N, Singh MP (2006) A Study on the Association of Cytochrome-P450 1A1 Polymorphism and Breast Cancer Risk in North Indian Women. Breast Cancer Res Treat 101:73–81
Spurr NK, Gough AC, Stevenson K, Wolf CR (1987) Msp-1 polymorphism detected with a cDNA probe for the P-450 I family on chromosome 15. Nucleic Acids Res 15:5901
Taioli E, Bradlow HL, Garbers SV, Sepkovic DW, Osborne MP, Trachman J, Ganguly S, Garte SJ (1999) Role of estradiol metabolism and CYP1A1 polymorphisms in breast cancer risk. Cancer Detect Prev 23:232–237
Taioli E, Trachman J, Chen X, Toniolo P, Garte SJ (1995) A CYP1A1 restriction fragment length polymorphism is associated with breast cancer in African-American women. Cancer Res 55:3757–3758
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This research was supported by Grant 2006AA02Z324 from the National High Technology Research and Development Program of China (863 Program).
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Chen, C., Huang, Y., Li, Y. et al. Cytochrome P450 1A1 (CYP1A1) T3801C and A2455G polymorphisms in breast cancer risk: a meta-analysis. J Hum Genet 52, 423 (2007). https://doi.org/10.1007/s10038-007-0131-8
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DOI: https://doi.org/10.1007/s10038-007-0131-8
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