尿液中雙酚A濃度和雌激素受體基因 與乳癌之相關性研究

Association between urine Bisphenol A concentration, gene expression of estrogen receptor and Breast Cancer.

高勝農(Sheng-Nung Kao)

指導教授 ： 王姿乃

高雄醫學大學/健康科學院/公共衛生學系公共衛生學碩士班/碩士(2015年)

摘要

研究背景:
乳癌為婦女族群中最常見之癌症之一，而儘管科學技術及醫學水準不斷改革演進，相較於過去已能顯著提前發現癌變徵兆的時間以及術後存活的機會，但在發生率方面從過去二十餘年至今，仍然呈現一個正向成長的趨勢。目前對於雌激素受體基因表現在乳癌病程所扮演的角色已有許多文獻證實，而Bisphenol A(BPA)卻較侷限於以細胞及動物實驗為主。本研究主旨在嘗試以病例對照研究，於雌激素相關路徑尋找BPA對於乳癌的致病機轉，觀察ESR1、ESR2、ESRRA、ESRRB等雌激素受體調控基因與BPA濃度在病例與對照組間所呈現之情形。
材料方法:
本研究之個案來自高雄醫學大學附設中和紀念醫院乳房外科，排除良性個案並經由專科醫師診斷為乳癌，願意簽署人體試驗同意書參與問卷訪視20歲以上之患者，最後選取147位病患與54位對照，測量尿液中BPA濃度及部分受試者血液中之雌激素受體基因表現量。所有參與研究之個案，其問卷填答都是經由受過訓練之訪視人員進行訪視，問卷內容包含基本人口學資料、職業暴露史、家族史、環境暴露、飲食習慣及過去疾病史等資料。
結果:
經統計分析檢定結果發現病例組尿液中BPA濃度顯著高於對照組，而人口學變項及乳癌危險因子並無顯著差異。將BPA濃度進行四分位數分組，利用卡方檢定可觀察到其分佈在病例對照組有顯著差異；再者利用邏輯式回歸在控制不同變數的情況下觀察BPA濃度對於罹患乳癌風險之影響，發現在校正干擾因子後，除了quartile2外罹患乳癌之風險皆有隨BPA濃度顯著上升之情形，且在校正年齡、BMI與額外校正流產經驗、初經年齡之兩個模型中，quartile 4(>0.0643 mg/g Cr.)相對於quartile 1(<0.0072 mg/g Cr.)分別有3.41與14.1倍的罹病風險。最後，在相關分析中發現BPA與ESR2無論在有無校正年齡與BMI之模型中皆呈顯著之正相關。
討論與結論:
本研究發現病例較對照組其尿液中BPA濃度較高，且不論以類別變項或連續變項進行分析，對於增加罹患乳癌風險都有顯著意義。另外，也發現BPA與雌激素受體基因ESR2呈顯著之正相關，推測BPA可能直接或間接影響ESR2之表現，造成罹患乳癌風險增加。

關鍵字

乳癌 ； 雙酚A

並列摘要

Introductions
Breast cancer is the most common disease in woman, and the incidence rate has been growing for over twenty years. The improvement of medical technology can detect the disease earlier and increase the survival rate, There are several researches proving the role of estrogen receptor in oncogenic mechanism, but relative fewer articles discussed about the effect of bisphenol A (BPA). The aim of this study is to explore the pathway of BPA on the risk of breast cancer in a case-control study, and find the differences of expression levels of estrogen receptor related genes and urinary BPA concentrations in breast cancer patients and healthy control.
Materials and Methods
Breast cancer patients of this study were recruited from Kaohsiung Medical University Hospital and healthy controls were recruited from communities in Kaohsiung, They are willing to sign the informed consent and over twenty years old. Breast cancer cases are diagnosed by physicians with the pathological lesion report. We excluded the patients with benign breast disorders and who have been diagnosed to have cancer before. At last, we included 147 cases and 54 healthy controls to measure urinary BPA concentrations and expression levels of estrogen receptor genes.
Results
This study find that the urinary BPA concentration is significant higher in case group than in control group. Analysis of urinary BPA concentration as category variables with quartile distribution, we found that the risk of breast cancer increase along with higher BPA concentration by running logistic regression model and the odds ratio is 5.98 and 14.1 for the third (0.02179-0.0643 mg/g Cr.) and fourth (>0.0643mg/g Cr.) quartile groups compared to the reference quartile group (<0.0072 mg/g Cr.) after adjusting for age, BMI, abortion experience and menarche age. Log-transform expression level of ESR2 is significant positive associated with BPA concentration in general linear regression with adjusted for age and BMI.
Conclusions
The present study find that BPA exposure could significant increase the risk of breast cancer, and positively regulate the expression level of ESR2 gene. We speculate that BPA may increase the expression of ESR2 and further induce the increasing risk of breast cancer.

並列關鍵字

Breast cancer ； Bisphenol A

參考文獻

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