UGT1A7 之低活性與肺癌之相關性：案例對照初步研究   全文下載

Association of Low Activity of UGT1A7 with Lung Cancer in Taiwan: A Preliminary Case Control Study

本 研 究 主 要 評 估 台 灣 族 群 中，UDP-glucuronosyltransferases1A7 (UGT1A7)基因多型性與肺癌致病危險性之相關性。本病例對照研究中共納入230個肺癌病人及年紀、性別配對之健康人。UGT1A7*1定義為高活性對偶基因，UGT1A7*2, UGT1A7*3及UGT1A7*4 則為低活性對偶基因。本研究同時分析epidermal growth factor receptor (EGFR)突變與UGT1A7基因多型性之關係。結果顯示UGT1A7*2, UGT1A7*3於肺癌病人之出現頻率較對照組為高（p = 0.03; odds ratio, OR, 1.44; 95% confidence interval (CI), 1.04 - 1.99 for UGT1A7*2; and p = 0.01; OR, 1.56; 95% CI, 1.11 - 2.18 for UGT1A7*3）。同時低活性基因型於肺癌病人出現之頻率亦較對照組為高（p = 0.03; OR, 1.58; 95% CI, 1.04 - 2.40 for the H/L group; and p < 0.01; OR, 2.23; 95% CI, 1.29 - 3.84 for the L/L group）。次族群分析發現此現象只在男性族群有顯著差異（OR, 1.87, 95% CI, 1.05 - 3.36, p = 0.03, for the high-activity allele/low-activity allele (H/L) group; OR, 2.638, 95% CI, 1.28 - 5.42, p < 0.01 for the high-activity allele/low-activity allele (L/L) allele group）。同時EGFR突變與病理分類並不影響UGT1A7之基因多型性分布。本研究結果初步顯示UGT1A7此代謝藥物之基因的多型性可能降低酵素活性，進而影響致癌物之解毒過程。故此可推斷UGT1A7基因多型性與台灣族群肺癌致癌過程有關。"

This study was aimed to evaluate the correlation between the polymorphisms of the UDP-glucuronosyltransferases1A7 (UGT1A7) gene and the risk of lung carcinogenesis in the Taiwanese population. A total of 230 lung cancer patients and 230 age- and gender-matched healthy individuals were enrolled in this case control study. UGT1A7*1 was defined as a high activity allele, while UGT1A7*2, UGT1A7*3 and UGT1A7*4 were categorized as low activity alleles. The relationship between EGFR mutations and UGT1A7 polymorphisms was investigated in this study. The frequency of UGT1A7*2 and UGT1A7*3 was significantly higher in the lung cancer group than in the control group (p = 0.03, odds ratio (OR) = 1.44, 95% confidence interval (CI) = 1.04 - 1.99 for UGT1A7*2; and p = 0.01, OR = 1.56, 95% CI = 1.11 - 2.18 for UGT1A7*3). The frequency of lower activity alleles was significantly higher in the lung cancer group than in the control group (p = 0.03, OR = 1.58, 95% CI = 1.04 - 2.40 for the high-activity allele/low-activity allele (H/L) group; and p < 0.01, OR = 2.23, 95% CI = 1.29 - 3.84 for the low-activity allele/low-activity allele (L/L) group). This difference was only significant in the male subgroup, with odds ratio of 1.87 (95% CI = 1.05 - 3.36, p = 0.03) for the H/L group and 2.638 (95% CI = 1.28 - 5.42, p < 0.01) for the L/L allele group. Yet, pathologic type and epidermal growth factor receptor (EGFR) mutations did not affect the distribution of UGT1A7 in the patient group. The results suggested that the polymorphisms of the metabolic gene, UGT1A7, may contribute to reduced enzyme activity and subsequently affect the detoxification of carcinogens. It is therefore concluded that UGT1A7 polymorphism is associated with lung carcinogenesis for the Taiwanese population.