||A population-based case-control study on the associations of Angelica sinensis with breast cancer
||Graduate Institute of Public Health(on the job class)
Health insurance database
A population-based case-control study on the association of herbal Angelica sinensis exposure with risk of breast cancer
Department of Public Health & College of Medicine National Cheng Kung University
This case-control study, including 34,262 women with breast cancer diagnosis and 102,786 matched controls identified from medical claims of 1-million Taiwan’s National Health Insurance program beneficiaries in 2005-2008, was conducted to investigate the relationships between Angelica sinensis and breast cancer. After controlling potential confounding factors, we found that the use of single and compound prescription of Angelica sinensis and breast cancer risk showed a weak but significant protective effect. Further analysis of the dose-response relationship also showed that the protective effect was positively correlated with the increase in the dose of the single and compound prescription of Angelica sinensis, and the trend test also revealed statistically significant. In addition, the analysis of the induction period of Angelica still showed that the protective effect was positively correlated with the increase of the induction period of Angelica sinensis. Besides, we found that the protective effect of Angelica reached related peak under the first Angelica exposure during the 47-55 years old. In the end, we also attempted to analyze other herbs which was known contained phytohormone include Pueraria and Dioscorea polystachya. And the adjusted odds ratio of breast cancer was similar to the exposure of Angelica sinensis revealed statistically weak protective effect or no statistical difference.
Since hormone replacement therapy had been found to increase the risk of breast cancer, the scientists also had concerns about the breast cancer carcinogenic effect of phytohormone contained in herbs of traditional Chinese medicines, especially Angelica, which is commonly used to improve gynecological menopausal symptoms. In the related research of Angelica, some researchers found that Angelica extract could stimulate the proliferation of breast cancer cells. However, the results observed in the subsequent experiments were not consistent. It was even observed that some Angelica extract had anti-cancer effects such as inhibiting estrogen activity or promoting apoptosis of breast cancer cells. By far, there is no consensus on the issue of angelica and breast cancer risk relationship. Therefore, the study was conducted to investigate the association of Angelica sinensis with breast cancer risk in women by retrospective use of Taiwan's health insurance database. It was expected that the results of this study can provide better epidemiological evidence for the long-term debate over the putative link between angelica and breast cancer risk.
MATERIAL AND METHODS
We conducted a case-control study design based on Taiwan’s National Health Insurance claim data (medical claims of all cancer patients and of a random sample of 1-million people registgered in 2005) released by the National Health Research Institutes. The case series was all newly diagnosed breast cancer patient with catastrophic illness registration in Taiwan between 2005-2008; the control group was randomly selected from the 1-million beneficiaries who registered with the National Health Insurance program in 2005 who had no breast cancer diagnosis between 2000 and 2008. We employed the time density sampling method to select controls who were matched to case on date of breast cancer diagnosis and age, with a case/control ratio of 1/3. Exposure of angelica and other potential confounders was retrospectively retrieved between 2000/1/1 and date of breast cancer diagnosis. Logistic regression models were used in the analysis with SAS 9.4.
After controlling for potential confounders, we found that the use of single and compound prescription of Angelica sinensis and breast cancer risk showed a weak but significant protective effect, the covariate adjusted odds ratio of breast cancer incidence was 0.93 (95% confidence interval 0.90-0.96; P value <0.0001). Further analysis of the dose-response relationship also showed that the protective effect was positively correlated with the dose of single and compound prescription of Angelica sinensis; and the trend test was statistically significant. In addition, the analysis of the induction period of Angelica showed that the protective effect was positively correlated with the duration of exposure to Angelica sinensis. And we found that the protective effect of Angelica sinensis became statistically significant after five years of exposure. Besides, we found that the protective effect of Angelica reached related peak for the first Angelica exposure at 47-55 years of age, with an adjusted odds ratio of 0.89 (95% confidence interval 0.85-0.93; P value <0.0001). We also attempted to analyze other herbs which was known to contain phytohormone including Pueraria and Dioscorea polystachya. Similar to the effect of Angelica sinensis, the aOR of breast cancer associated with Pueraria and Dioscorea also suggested null or weak but significantly protective effect.
This population-based case-control study suggested that exposure to Angelica sinensis showed a weak but significant protective effect on breast cancer risk. The results remained intact after various falsification approaches and sensitivity analyses.
第1章 前言 1
1.1 研究目的 2
第2章 文獻回顧 3
2.1 當歸之簡介 3
2.2 當歸與乳癌之相關研究 3
2.3 當歸相關研究小結 5
2.4 乳癌之簡介 6
2.5 乳癌之危險因子 6
2.5.1 乳癌病史 6
2.5.2 乳癌家族史 6
2.5.3 年齡 7
18.104.22.168 初經與更年期年齡 7
2.5.4 肥胖 8
2.5.6 內源性荷爾蒙 9
22.214.171.124 雌激素 9
2.5.7 其他危險因子 9
126.96.36.199 骨質密度 9
188.8.131.52 身高 10
184.108.40.206 良性乳腺疾病 10
2.5.8 台灣健保資料庫乳癌風險研究 10
2.6 乳癌文獻小結 11
第3章 材料與方法 12
3.1 研究問題 12
3.3 研究設計 14
3.3.1 研究對象定義與選取 15
3.3.2 當歸暴露的操作型定義 16
3.3.3 各類危險因子操作型定義 16
3.3.4 人口基本資料定義與擷取 17
3.4 資料分析 17
3.4.1 描述性統計 17
3.4.2 分析性統計 17
3.4.3 敏感度分析 18
第4章 結果 20
4.1 基本資料 20
4.2 當歸暴露與乳癌發生之勝算比 21
4.3 當歸暴露與乳癌發生之劑量反應關係 22
4.4 當歸暴露期時間長短與乳癌風險 23
4.5 否證分析 – 針灸暴露與乳癌風險 24
4.6 更年期與當歸對乳癌發病風險之影響 25
4.7 敏感度分析 – 黃體酮 25
4.8 敏感度分析 – 乳房良性腫瘤 26
4.9 含植物性荷爾蒙中藥與乳癌風險觀察 27
第5章 討論 29
5.1 當歸的乳癌風險分析結果 29
5.2 過去文獻比較與相關機轉討論 29
5.3 研究優勢與限制 31
5.3.1 研究優勢 31
5.3.1 研究限制 31
第6章 結論 33
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