https://scholars.lib.ntu.edu.tw/handle/123456789/477855
標題: | Breast cancer risk associated with genotype polymorphism of the catechol estrogen-metabolizing genes: A multigenic study on cancer susceptibility | 作者: | Cheng T.-C. Chen S.-T. CHIUN-SHENG HUANG Fu Y.-P. Yu J.-C. Cheng C.-W. Wu P.-E. Shen C.-Y. |
公開日期: | 2005 | 卷: | 113 | 期: | 3 | 起(迄)頁: | 345-353 | 來源出版物: | International Journal of Cancer | 摘要: | Estrogen has been suggested to trigger breast cancer development via an initiating mechanism involving its metabolite, catechol estrogen (CE). To examine this hypothesis, we carried out a multigenic case-control study of 469 incident breast cancer patients and 740 healthy controls to define the role of important genes involved in the different metabolic steps that protect against the potentially harmful effects of CE metabolism. We studied the 3 genes involved in CE detoxification by conjugation reactions involving methylation (catechol-O-methyltransferase, COMT), sulfation (sulfotransferase 1A1, SULT1A1), or glucuronidation (UDP-glucuronosyltransferase 1A1, UGT1A1), one (manganese superoxide dismutase, MnSOD) involved in protection against reactive oxidative species-mediated oxidation during the conversion of CE-semiquinone (CE-SQ) to CE-quinone (CE-Q), and 2 of the glutathione S-transferase superfamily, GSTM1 and GSTT1, involved in CE-Q metabolism. Support for this hypothesis came from the observations that (i) there was a trend toward an increased risk of breast cancer in women harboring a greater number of putative high-risk genotypes of these genes (p < 0.05); (ii) this association was stronger and more significant in those women who were more susceptible to estrogen [no history of pregnancy or older (?26 years) at first full-term pregnancy (FFTP)]; and (iii) the risks associated with having one or more high-risk genotypes were not the same in women having experienced different menarche-to-FFTP intervals, being more significant in women having been exposed to estrogen for a longer period (?12 years) before FFTP. Furthermore, because CE-Q can attack DNA, leading to the formation of double-strand breaks (DSB), we examined whether the relationship between cancer risk and the genotypic polymorphism of CE-metabolizing genes was modified by the genotypes of DSB repair genes, and found that a joint effect of CE-metabolizing genes and one of the two DSB repair pathways, the homologous recombination pathway, was significantly associated with breast cancer development. Based on comprehensive CE metabolizing gene profiles, our study provides support to the hypotheses that breast cancer can be initiated by estrogen exposure and that increased estrogen exposure confers a higher risk of breast cancer by causing DSB to DNA. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-11144304064&doi=10.1002%2fijc.20630&partnerID=40&md5=44884bda02c20e3d9deca0f84ec00aa8 https://scholars.lib.ntu.edu.tw/handle/123456789/477855 |
ISSN: | 0020-7136 | DOI: | 10.1002/ijc.20630 | SDG/關鍵字: | 1,4 benzoquinone; catechol estrogen; catechol methyltransferase; double stranded DNA; manganese superoxide dismutase; reactive oxygen metabolite; semiquinone; sulfotransferase; adult; aged; article; breast cancer; cancer risk; cancer susceptibility; conjugation; controlled study; detoxification; DNA strand breakage; female; gene function; genetic polymorphism; genetic recombination; genotype; glucuronidation; human; human experiment; major clinical study; menarche; methylation; nucleotide metabolism; oxidation; pregnancy; priority journal; risk assessment; sulfation; Adult; Aged; Aged, 80 and over; Arylsulfotransferase; Breast Neoplasms; Carcinoma, Ductal, Breast; Case-Control Studies; Catechol O-Methyltransferase; DNA; DNA Repair; Estrogens, Catechol; Female; Genetic Predisposition to Disease; Genotype; Glucuronosyltransferase; Glutathione Transferase; Humans; Middle Aged; Polymorphism, Genetic; Risk Factors; Superoxide Dismutase; Taiwan; Tumor Markers, Biological |
顯示於: | 醫學系 |
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