腎細胞癌及尿路上皮細胞癌與尿中及腎臟皮質、腎盂、輸尿管組織中金屬元素關係之探討

國外許多流行病學研究中皆發現金屬暴露與癌症的關係，國內也有研究發現砷的暴露與尿路上皮細胞癌之間有顯著的劑量反應關係存在。動物實驗中，暴露砷、鎘、鉛與鎳等也被報導與腎臟腫瘤發展有關，但目前金屬暴露在腎臟癌發生機制所扮演的角色仍未有定論。因此，本研究目的為探討多元素在腎臟癌個案尿中及腎皮質、腎盂、輸尿管中之濃度分布，期望能進一步了解金屬暴露與腎臟癌發生的關係。本研究中招募了41名來自於台大醫院泌尿部的尿路上皮細胞癌與11名腎細胞癌個案，還有8名對照個案。腎臟癌個案在經過病理學的判定確認後，將依照TNM癌症分類系統進行癌症病程的分級。另以問卷收集個案之年齡、身高、體重、職業、抽菸、規律喝酒、飲食習慣、中草藥使用與家族及病史等資料。腎皮質、腎盂、輸尿管組織樣本經由密閉式之微波消化系統，再由ICP-MS進行正常組織與腫瘤組織樣本中金屬濃度之分析。尿液樣本先經過0.45 μm的濾膜過濾，再透過ICP-MS分析尿中金屬之濃度。研究結果顯示，不同癌症病程的腎臟癌病人，尿中各種金屬濃度差異在統計上未達顯著。腎皮質及腎盂正常組織中砷、鎘、錳與銅濃度高於同部位腫瘤組織，其中鎘在上述兩腎臟部位正常組織皆顯著高於相對腫瘤組織，砷與鍶在腎皮質正常組織中濃度顯著比同部位腫瘤組織高。輸尿管腫瘤組織中砷、鎘、錳與銅濃度較正常組織高，其中砷與鎘在輸尿管正常與腫瘤兩組織間差異達統計上顯著。總結來說，各種金屬在腎皮質、腎盂與輸尿管的正常組織與腫瘤組織中濃度分布不同，推測可能是由於腫瘤細胞快速增生或金屬硫蛋白在腫瘤細胞中大量表現所導致，確實的形成機制亟待未來進一步研究探討。

關鍵字

重金屬；尿；腎皮質；腎盂；輸尿管；腎臟癌；尿路上皮細胞癌

並列摘要

Several epidemiological studies reported the association between trace metals exposure and cancers. In Taiwan, a significant dose-response relationship between arsenic exposure and urothelial cell carcinoma was also demonstrated. Besides, animal studies showd tumor growth in animals exposed to arsenic, cadmium, lead and nickel. However, the roles of trace metals in the development of kidney cancer are unclear. The purpose of this study was to characterize the distribution of trace metals in urine and in renal cortex, pelvis, and ureter of the study subjects to further explore the relationship between trace metals and kidney cancer. In this study, 41 urothelial cell carcinoma (UCC) cases, 11 renal cell carcinoma (RCC) cases, and 8 controls were obtained from the Urological Department of the National Taiwan University Hospital. All UCC and RCC subjects were histologically diagnosed and classified according to the TNM classification system. Questionnaire was admintered to collect individual’s information, such as age, body height, weight, smoking history, occupation, alcohol drinking, dietary habit, herbal medicine uses, and familial disease history. Normal and tumor tissue samples of renal cortex, renal pelvis, and ureter were decomposed by using a microwave-assisted method in closed vessels. The inductively coupled plasma mass spectrometry was used to determine the contents of trace metals in normal and tumor renal tissue. Urine sample was first filtered through a 0.45-μm membrane prior to being analysed by ICP-MS. In this study no significant difference was found in urinary metal levels of kidney cancer cases among different stages. With respect to trace metals in renal tissues, the concentrations of cadmium in normal tissues were significantly higher than in tumor tissues of both renal cortex and pelvis, respectively, whereas the concentrations of arsenic and strontium in normal tissues were significantly higher than in tumor tissue only in renal cortex. For ureter, the concentrations of arsenic and cadmium in tumor tissue were significantly higher than in normal tissue, while those of manganese and copper in tumor tissue were also higher, though not statisticaly significantly, than in normal tissue. In summary, the concentrations of various trace metals in tumor and normal tissues differed in cortex, pelvis, or ureter, which might be caused by the fast proliferation of tumor cell or the over-expression of metallothionein in tumor cell. However, the real mechanism is still warrants further studies.

並列關鍵字

Heavy metals ； Urine ； Renal cortex ； Renal pelvis ； Ureter ； Kidney cancer ； Urothelial cell carcinoma

參考文獻

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腎細胞癌及尿路上皮細胞癌與尿中及腎臟皮質、腎盂、輸尿管組織中金屬元素關係之探討

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