Summary
The incidence of breast cancer has been greatly increasing in Taiwan over the past two decades. Since cytochrome P4501A1 (CYP1A1) is involved in the metabolism of environmental carcinogens or oestrogen, we hypothesized that CYP1A1 genetic polymorphism may be a susceptibility factor for breast cancer. This hypothesis was evaluated in this case control study of 150 breast cancer patients and 150 healthy controls among Chinese women. Two CYP1A1 polymorphisms were studied, one containing a new Msp1 site and the other located in axon 7 and resulting in the replacement of an isoleucine (Ile) residue by a valine (Val). After simultaneously considering the known or significant risk factors for breast cancer, including the age of study participants, positive family history of breast cancer, early menarche (≤ 13 years), nulliparity and late first full-term pregnancy (≥ 30 years), hormone replacement therapy and smoking, the CYP1A1 Msp1 polymorphism was found to be a significant factor in determining the risk of breast cancer. The homozygous variant was the most susceptible genotype with an adjusted odds ratio of 1.98 (95% confidence interval (CI) = 1.01–3.99) compared with the non-homozygous variants (the homozygous wild-type and the heterozygous variant). In contrast, the CYP1A1 Ile/Val polymorphism was not significantly associated with breast cancer development (adjusted OR = 1.07, 95% CI = 0.64–1.78). Interestingly, the Msp1 polymorphism was especially significant in postmenopausal women, but not in premenopausal women. Further stratification analysis in postmenopausal women who were non-smokers and with no history of hormone replacement therapy showed the cancer risk due to the Msp1 variant to be more significant in women with early menarche. We conclude that CYP1A1 polymorphism is a susceptibility factor for breast cancer in postmenopausal Chinese women in Taiwan. Further study with a large sample size should be considered to address issues of interactions between CYP1A1 and other risk factors.
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Alexandrie, A. K., Sundberg, M. I., Seidegard, J., Torniling, G. & Rannug, A. (1994). Genetic susceptibility to lung cancer with special emphasis on CYP1A1 and GSTM1: a study on host factors in relation to age at onset, gender and histological cancer types. Carcinogenesis 15: 1785–1790.
Ambrosone, C. B., Freudenheim, J. L., Graham, S., Marshall, J. R., Vena, J. E., Brasure, J. R., Laughlin, R., Nemoto, T., Michalek, A. M., Harrington, A., Ford, T. D. & Shield, P. G. (1995). Cytochrome P4501A1 and glutathione S-transferase (M1) genetic polymorphism and postmenopausal breast cancer risk. Cancer Res 55: 3483–3485.
Bailey, L. R., Roodi, N., Verrier, C. S., Yee, C. J., Dupont, W. D. & Parl, F. F. (1998). Breast cancer and CYP1A1, GSTM1 and GSTT1 polymorphism: evidence of a lack of association in Caucasians and African Americans. Cancer Res 58: 65–70.
Ball, S. E., Forrester, L. M., Wolf, C. R. & Back, D. J. (1990). Differences in the cytochrome P450 isoenzymes involved in the 2-hydroxylation of estradiol and 17α-ethinylestradiol. Biochem J 267: 221–226.
Bernstein, L., Yuan, J. M., Ross, R. K., Pike, M. C., Hanisch, R., Lobo, R., Stanczyk, F., Gao, Y. T. & Henderson, B. E. (1990). Serum hormone levels in pre-menopausal Chinese women in Shanghai and white women in Los Angeles: results from two breast cancer case-control studies. Cancer Causes Control 1: 51–58.
Chie, W. C., Lee, W. C., Li, C. Y., Huang, C. S., Chang, K. J., Yen, M. L. & Lin, R. S. (1997). Lactation, lactation suppression hormones and breast cancer: a hospital-based case-control study for parous women in Taiwan. Oncol Rep 4: 319–326.
Chie, W. C., Li, C. Y., Huang, C. S., Chang, K. J. & Lin, R. S. (1998). Body size factors of different ages and breast cancer risk in Taiwan. Anticancer Res 18: 565–570.
Drakoulis, N., Cascorbi, I., Brockmoller, J., Gross, C. R. & Roots, I. (1994). Polymorphism in the human CYP1A1 gene as susceptibility factors for lung cancer: exon-7 mutation (4889 A to G), and a T to C mutation in the 3′-flanking region. Clin Invest 72: 240–248.
Fishman, J., Schneider, J., Hershcope, R. J. & Bradlow, H. L. (1984). Increased estrogen-16α-hydroxylase activity in women with breast and endometrial cancer. J Steroid Biochem 20: 1077–1081.
Hayashi, S. I., Watanabe, J., Nakachi, K. & Kawajiri, K. (1991). Genetic linkage of lung cancer-associated Msp1 polymorphism with amino acid replacement in the heme binding region of the human cytochrome P4501A1 gene. J Biochem 110: 407–411.
Hirvonen, A., Husgafvel-Pursiainen, K., Karjalainen, A., Anttila, S. & Vainio, H. (1992). Point-mutational Msp1 and Ile-Val polymorphism closely linked in the CYP1A1 gene: lack of association with susceptibility to lung cancer in a Finnish study population. Cancer Epidemiol Biomarkers Prev 1: 485–489.
Hunter, D. J. & Willett, W. C. (1993). Diet, body size, and breast cancer. Epidemiol Rev 15: 110–132.
Ishibe, N., Hankinson, S. e., Colditz, G. A., Spiegelman, D., Willett, W. C., Speizer, F. E., Kelsey, K. T. & Hunter, D. J. (1998). Cigarette smoking, cytochrome P4501A1 polymorphism, and breast cancer risk in the nurses health study. Cancer Res 58: 667–671.
Kato, S., Bowman, E. D., Harrington, A. M., Blomeke, B. & Shields, P. G. (1995). Human lung carcinogen-DNA adduct levels mediated by genetic polymorphism in vivo. J Natl Cancer Inst 87: 902–907.
Kawajiri, K., Nakachi, K., Imai, K., Yoshii, A., Shinoda, N. & Watanabe, J. (1990). Identification of genetically high risk individuals to lung cancer by DNA polymorphism of the cytochrome P4501A1 gene. FEBS Lett 263: 131–133.
Kawajiri, K., Nakachi, K., Imai, K., Watanabe, J. & Hayashi, S. (1993). The CYP1A1 gene and cancer susceptibility. Crit Rev Oncol Hematol 14: 77–87.
Kelsey, J. L. (1993). Breast cancer epidemiology: summary and future directions. Epidemiol Rev 15: 36–47.
Kihara, M. & Noda, K. (1995). Risk of smoking for squamous and small cell carcinomas of the lung modulated by combinations of CYP1A1 and GSTM1 gene polymorphism in a Japanese population. Carcinogenesis 16: 2331–2336.
Kleinbaum, D. G., Kupper, L. L. & Morgenstern, H. (1982). Epidemiologic Research. Van Nostrand Reinhold: New York
Li, D., Wang, M., Dhingra, K. & Hittelman, W. N. (1996). Aromatic DNA adducts in adjacent tissues of breast cancer patients: clues to breast cancer etiology. Cancer Res 56: 287–293.
Lo, Y. L., Yu, J. C., Huang, C. S., Tseng, S. L., Chang, T. M., Chang, K. J., Wu, C. W. & Shen, C. Y. (1998). Allelic loss of the BRCA1 and BRCA2 genes and other regions on 17q and 13q in breast cancer among women from Taiwan (area of low incidence but early onset). In J Cancer 79: 580–587.
Nakachi, K., Imai, K., Hayashi, S., Watanabe, J. & Kawajiri, K. (1991). Genetic susceptibility to squamous cell carcinoma of the lung in relation to cigarette smoking dose. Cancer Res 51: 5177–5180.
Osborne, M. P., Bradlow, H. L., Wong, G. Y. & Telang, N. T. (1993). Upregulation of estradiol C16α-hydroxylation in human breast tissue: a potential biomarker of breast cancer risk. J Natl Cancer Inst 85: 1917–1920.
Oyama, T., Mitsudomi, T., Kawamoto, T., Ogami, A., Osaki, T., Kodama, Y. & Yasumoto, K. (1995). Detection of CYP1A1 gene polymorphism using designed RFLP and distributions of CYP1A1 genotypes in Japanese. Int Arch Occup Environ Health 67: 253–256.
Perera, F. P., Estabrook, A., Hewer, A., Channing, K., Rundle, A., Mooney, L. A., Whyatt, R. & Phillips, D. H. (1995). Carcinogen-DNA adducts in human breast tissue. Cancer Epidemiol Biomarkers Prev 4: 233–238.
Taioli, E., Trachman, J., Chen, X., Toniolo, P. & Garte, S. J. (1995). A CYP1A1 restriction fragment length polymorphism is associated with breast cancer in African-American women. Cancer Res 55: 3757–3758.
Yager, J. D. (1996). Molecular mechanisms of estrogen carcinogenesis. Annu Rev Pharmacol Toxicol 36: 203–232.
Yang, P. S., Yang, T. L., Liu, C. L., Wu, C. W. & Shen, C. Y. (1997). A case-control study of breast cancer in Taiwan: a low incidence area. Br J Cancer 75: 752–756.
Xu, X., Kelsey, K. T., Wiencke, J. K., Wain, J. C. & Christiani, D. C. (1996). Cytochrome P450 CYP1A1 Msp1 polymorphism and lung cancer susceptibility. Cancer Epidemiol Biomarkers Prev 5: 687–692.
Zhang, Z. Y., Fasco, M. J., Huang, L., Guengerich, F. P. & Kaminsky, L. S. (1996). Characterization of purified human recombinant cytochrome P4501A1-Ile and -Val462: Assessment of a role for the rare allele in carcinogenesis. Cancer Res 56: 3926–3933.
Zhu, B. T. & Conney, A. H. (1998). Functional role of estrogen metabolism in target cells: review and perspectives. Carcinogenesis 19: 1–27.
Ziegler, R. G., Hoover, R. N., Pike, M. C., Hildesheim, A., Nomura, A. M., West, D. W., Wu-Williams, A. H., Kolonel, L. N., Horn-Ross, P. L., Rosenthal, J. F. & Hyer, M. B. (1993). Migration patterns and breast cancer risk in Asian-American women. J Natl Cancer Inst 85: 1819–1827.
Author information
Authors and Affiliations
Additional information
Departments of Pathology, National Taiwan University, No. 1 Jen-Ai Road, Sec. 1, Taipei, Taiwan
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Huang, CS., Shen, CY., Chang, KJ. et al. Cytochrome P4501A1 polymorphism as a susceptibility factor for breast cancer in postmenopausal Chinese women in Taiwan. Br J Cancer 80, 1838–1843 (1999). https://doi.org/10.1038/sj.bjc.6690608
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bjc.6690608
Keywords
This article is cited by
-
Meta-analysis of genetic polymorphisms in xenobiotic metabolizing enzymes and their association with breast cancer risk
Journal of Genetics (2018)
-
Lack of significant association between CYP1A1 T3801C polymorphism and breast cancer risk: a meta-analysis involving 25,087 subjects
Breast Cancer Research and Treatment (2010)
-
Four polymorphisms in cytochrome P450 1A1 (CYP1A1) gene and breast cancer risk: a meta-analysis
Breast Cancer Research and Treatment (2010)
-
Polymorphism of cytosolic serine hydroxymethyltransferase, estrogen and breast cancer risk among Chinese women in Taiwan
Breast Cancer Research and Treatment (2008)
-
Genetic polymorphisms in oestrogen metabolic pathway and breast cancer: a positive association with combined CYP/GST genotypes
Clinical and Experimental Medicine (2008)