以血清濃度推估多氯聯苯及多氯呋喃高暴露族群之癌症風險

Abstract

戴奧辛類化合物是一群具有相似平面結構的化學物質，在環境及人體中不易被分解，是常見的環境污染物。這類化合物有著相同的特性，會以不同程度和芳香族碳氫化合物接受器結合產生相對應的毒性。

日本油症事件發生的十一年後，1979年，一場極為類似的悲劇也在台灣發生了。日本生產的多氯聯苯（PCB）混合物（Kanechlor400，500）被台灣中部的米糠油生產廠商當作脫臭及除色過程中的熱傳導介質，卻因為管線破裂使得多氯聯苯及其副產物多氯呋喃、多氯三苯及多氯四苯不慎滲入米糠油中，毒害了兩千多名食用該油品的民眾。這場事件起因於食用了受到污染的油品，因此我們將其稱作油症事件，暴露者則常被稱作油症患者。

為了檢測油症患者的血液多氯聯苯、多氯呋喃及多氯戴奧辛的濃度，我們在1994到2003年間採集了他們的血液樣本，儲存於-80℃中，並以乾冰運往美國疾病管制局做檢驗。該檢測結果是以身體中的脂肪做為基礎，計算血脂中的戴奧辛含量，而該戴奧辛含量則是以毒性當量因子推估而得的。 由於缺少了台灣油症患者1979年詳細的暴露資料以及暴露當時的血液樣本，加上到目前為止戴奧辛類化合物的癌症，並沒有確切的劑量反應關係，使得風險評估工作一直未能順利進行。我們只知道油症患者暴露到戴奧辛類物質會有得到癌症的危險，卻沒有辦法計算它。因此本研究希望利用油症患者與一般民眾血中累積戴奧辛濃度的比值，乘上一般民眾的癌症風險，進而估算油症患者的終生致癌風險值。 推估風險過程中，我們發展了比較風險模型概念，包含三個步驟： 步驟一，計算一般民眾和油症患者的終生累積濃度。 步驟二，利用已達穩定態的一般民眾推估終身平均日暴露劑量並計算其終生致癌風險。 步驟三，利用曲線下面積的比值計算出油症患者的終生致癌風險。 血液樣本共計245名的油症患者，包含了85位男性(34.7%)及160位女性(65.3%)，他們抽血時的平均濃度363 pg-TEQ/g-lipid (SD=340; 95% CI=321-406)，回推至1979年濃度則為1322 pg-TEQ/g-lipid (SD=1127; 95% CI=1181-1463)。根據台灣一般民眾所推出暴露到戴奧辛化合物的終生致癌風險為2.18*10-3以及曲線下面積比值13.8倍，可推出油症患者的終生致癌風險為3.01*10-2。 這是第一篇利用台灣多氯聯苯及多氯呋喃高暴露族群去推算癌症風險的研究，其中所利用的比較風險模型的概念，是以血中戴奧辛累積濃度為基礎，提供了一個計算癌症風險上較為客觀的方法。

Dioxin-like chemicals are composed of a group of substances with similar planar structure. They are very common environmental pollutants and not easy to be decomposed in the environment and human body. These chemicals have the same characteristic which combine with aryl hydrocarbon receptor (AhR) to different degrees and result in corresponding toxicity. Eleven years after the Japanese Yusho incident, a similar tragedy happened in Taiwan in 1979. A Japanese-produced polychlorinated biphenyl (PCB) mixture (Kanechlor 400, 500) was used as the heat-transfer medium in the process of deodorization and decolorization of rice oil by an rice oil company in central Taiwan. PCBs and their heat-degraded byproducts, polychlorinated dibenzofurans (PCDFs), ter-and quaterphenyls (PCTs and PCQs), leaked into the rice oil and poisoned 2000 people who had consumed the oil. Because the disease was caused by ingestion of rice oil, the syndrome was then referred to as Yucheng, and the exposed subjects were referred to as the Yucheng cohort. The blood samples were collected between 1994 and 2003, stored at -80 °C, and sent on dry ice to the U.S. Centers for Disease Control and Prevention for the measurements of PCB, PCDF, and PCDD congeners. Values were reported on a lipid weight basis in parts per trillion (ppt) by dividing the congeners on a whole-weight basis by total serum lipid content, estimated from measurements of triglycerides, and total cholesterol. TCDD toxic equivalency (TEQ) was calculated as the sum of the product of each analyte concentration and its TEF. Limited by incomplete exposure data of Taiwan Yucheng patients and no consistent conclusions of the exact dose-response relation of cancer, the risk assessment work is not available for a long time. In this study, the excess cancer risk of Yucheng population was calculated by multiplying the excess risk of the background population by the ratio of cumulative serum level between Yucheng and background population. For risk estimation, the comparative risk model with three steps as follows： Step 1：Lifetime cumulative conc. in background population and Yucheng subjects Step 2：Estimating the LADD and lifetime excess cancer risk of background population Step 3：Calculation of lifetime excess cancer risk in Yucheng population A total of 245 Yucheng subjects, including 85 (34.7%) men and 160 (65.3%) women donated blood for serum level measurements. The average serum concentration was 363 (SD=340; 95% CI=321-406) pg-TEQ/g-lipid. Serum levels of TCDD-TEQ was back-calculated to 1979, as 1322 (SD=1127; 95% CI=1181-1463) pg-TEQ/g-lipid. According to estimated dioxin LADD, the lifetime excess cancer risk caused by background exposure to dioxins is 2.18*10-3, and the corresponding value among Yucheng individuals is 3.01*10-2, namely, 13.8 times that of background population. This is the first study to estimate the excess cancer risk for humans due to high exposure to PCBs and PCDFs. The comparative risk model of this study is based on the blood dioxin cumulative concentration offering a more objective way to calculate possible excess cancer risk.