| DOI: | 10.2172/983194
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| 报告号: | LBNL-3324E
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| 报告题名: | Role of CYP1B1 in PAH-DNA adduct formation and breast cancer risk |
| 作者: | Goth-Goldstein, Regine; Russell, Marion L.; Muller, A.P.; Caleffi, M.; Eschiletti, J.; Graudenz, M.; Sohn, Michael D.
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| 出版年: | 2010
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| 发表日期: | 2010-04-01
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| 国家: | 美国
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| 语种: | 英语
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| 中文主题词: | 有机物
; 铅
; 碳氢化合物/烃类
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| 主题词: | ORGANIC MATTER
; LEAD
; HYDROCARBONS
|
| 英文摘要: | This study investigated the hypothesis that increased exposure to polycyclic aromatic hydrocarbons (PAHs) increases breast cancer risk. PAHs are products of incomplete burning of organic matter and are present in cigarette smoke, ambient air, drinking water, and diet. PAHs require metabolic transformation to bind to DNA, causing DNA adducts, which can lead to mutations and are thought to be an important pre-cancer marker. In breast tissue, PAHs appear to be metabolized to their cancer-causing form primarily by the cytochrome P450 enzyme CYP1B1. Because the genotoxic impact of PAH depends on their metabolism, we hypothesized that high CYP1B1 enzyme levels result in increased formation of PAH-DNA adducts in breast tissue, leading to increased development of breast cancer. We have investigated molecular mechanisms of the relationship between PAH exposure, CYP1B1 expression and breast cancer risk in a clinic-based case-control study. We collected histologically normal breast tissue from 56 women (43 cases and 13 controls) undergoing breast surgery and analyzed these specimens for CYP1B1 genotype, PAH-DNA adducts and CYP1B1 gene expression. We did not detect any difference in aromatic DNA adduct levels of cases and controls, only between smokers and non-smokers. CYP1B1 transcript levels were slightly lower in controls than cases, but the difference was not statistically significant. We found no correlation between the levels of CYP1B1 expression and DNA adducts. If CYP1B1 has any role in breast cancer etiology it might be through its metabolism of estrogen rather than its metabolism of PAHs. However, due to the lack of statistical power these results should be interpreted with caution. |
| URL: | http://www.osti.gov/scitech/servlets/purl/983194
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| Citation statistics: |
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| 资源类型: | 研究报告
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/39867
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| Appears in Collections: | 过去全球变化的重建
影响、适应和脆弱性
科学计划与规划
气候变化与战略
全球变化的国际研究计划
气候减缓与适应
气候变化事实与影响
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| 983194.pdf（616KB） | 研究报告 | -- | 开放获取 | | View
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| Recommended Citation: | |
Goth-Goldstein, Regine,Russell, Marion L.,Muller, A.P.,et al. Role of CYP1B1 in PAH-DNA adduct formation and breast cancer risk. 2010-01-01.
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