The Association Between Genetic Polymorphisms of the Estrogen-Metabolizing Genes CYP17, CYP1A1 and COMT and Risk of Breast Cancer：A Population-Based Nested Case-Control Study
| Autor: | Mei-Hsuan Wu, 吳美萱 |
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| Rok vydání: | 2001 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 89 Recent studies have provided important insights into the molecular tumorigenesis of breast cancer. Current understanding genetic markers responsible for susceptibility to breast cancer has led to an increasing number of epidemiological studies to define the contribution of relatively common genetic polymorphisms that may have a role in the metabolism of estrogens. The potential role of genetic variability in steroid hormone-metaboling genes including, cytochrome 17 (CYP17), CYP1A1, and catechol-O-methyltransferase (COMT), in the pathogenesis of breast cancer was evaluated by a case-control study nested within a population-based cohort study of major cancers in Taiwan. There were 64 incident breast cancer patients identified by data linkage with the national cancer registry system during the period between 1992 and 1998. Four controls, who were cancer-free at the time of diagnosis of cases, were matched to each case on age (2 years), residential areas, and date of blood collection (3 months). Information on sociodemographic characteristics, lifestyle habits, reproductive factors, and personal and family history of chronic diseases were obtained by a questionnaire interview during recuritment. In addition, genotypic polymorphism of CYP17, CYP1A1, and COMT were determined by polymerase chain reaction-restriction fragment length polymorphism methods based on banked blood specimens. Associations between specific genotypes and the development of breast cancer were examined by use of conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Study results show that the associations between genotypic polymorphism of CYP17, CYP1A1, and COMT and risk of breast cancer were as follows: the presence of CYP17 with at least one allele of A2 allele was found to be associated with an 1.8-fold (95% CI=0.8-4.2) increase in the risk of breast cancer; the presence of at least one allele of the CYP1A1 MspⅠvariant allele was related to an 1.4-fold (95% CI=0.8-2.6) increase in the risk of breast cancer; and the presence of at least one low-activity allele of COMT was associated with an OR of 0.8 (95% CI=0.5-1.5). In addition, results from the analysis of combined effect of genetic polymorphisms in CYP17, CYP1A1, and COMT revealed that the risk of breast cancer appeared to increase as the number of putative high-risk genotypes increased. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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