The Polymorphisms of Uridine-diphosphoglucuronosyltransferase 1A7 and 1A10 in Taiwanese Patients with Lung Cancer

台灣肺癌患者之尿甘雙磷酸葡萄糖醛酸基轉移脢第7/10同功酶基因多型性研究

蔡耀隆(Yao-Lung Tsai) ； 王淑貞(Shu-Chen Wang) ； 涂嘉明(Chia-Ming Twu) ； 姜泰安(Tai-An Chiang) ； 許舜斌(Shun-Pin Hsu) ； 洪崇仁(Tsung-Jen Hung) ； 黃慶三(Ching-Shan Huang) ； 吳義男(Yi-Nan Wu) ； 李又青(Yu-Ching Lee) ； 李貞堅(Zhen-Jian Lee) ； 黃雅芳(Ya-Fan Huang) ； 施盛棟(Sheng-Dong Shih) ； 吳佩芬(Pei-Fen Wu)

《Journal of Biomedical & Laboratory Sciences》 22卷4期 (2010/12) Pp. 141-149

https://doi.org/10.30046/JBLS.201012.0004

摘要

Several carcinogens mediated cellular injury are thought to play a crucial role in the pathogenesis of lung cancer. Additionally, genetic variations that reduce the expression or activity of detoxifying enzymes such as the UDP-glucuronosyltransferases might be important in this respect. The aim of this study is to investigate the hypothesis that frequency distribution of polymorphisms in the UGT1A7 and UGT1A10 genes is associated with occurrence of lung cancer in Taiwanese population. The method of polymerase chain reaction-restriction fragment length polymorphism was utilized to analyze nucleotides -57, 33, 387, 391, 392, and 622 of the UGT1A7 gene, and nucleotides 605, and 693 of the UGT1A10 gene for 100 lung cancer patients and 100 healthy controls. The results showed that lung cancer was inversely associated with the variation of UGT1A10 at nucleotide 693 (odds ratio [OR]: 0.276; 95% confidence interval [CI]: 0.097~0.787; p=0.011). The nucleotide changes of UGT1A7 at position -57, 33, and 622 showed significant correlation with position 387, 391, and 392 (r=0.52, p＜0.0001). Furthermore, we found that the risk of lung cancer had the higher level of frequency in haplotype of wild-type UGT1A10-693/variant UGT1A7-622 (OR: 8.77; 95% CI: 1.10~70.0; p=0.02). We did not detect any association between lung cancer and UGT1A7 polymorphisms in Taiwanese population. Nevertheless, this study demonstrated the novel findings that determination for nucleotide 693 of the UGT1A10 gene may be useful to identify individuals susceptible to lung cancer and take measures to prevent development of this disease.

關鍵字

肺癌 ； 尿甘雙磷酸葡萄糖醛酸基轉移脢 ； 基因多型性 ； 協同作用

並列摘要

Several carcinogens mediated cellular injury are thought to play a crucial role in the pathogenesis of lung cancer. Additionally, genetic variations that reduce the expression or activity of detoxifying enzymes such as the UDP-glucuronosyltransferases might be important in this respect. The aim of this study is to investigate the hypothesis that frequency distribution of polymorphisms in the UGT1A7 and UGT1A10 genes is associated with occurrence of lung cancer in Taiwanese population. The method of polymerase chain reaction-restriction fragment length polymorphism was utilized to analyze nucleotides -57, 33, 387, 391, 392, and 622 of the UGT1A7 gene, and nucleotides 605, and 693 of the UGT1A10 gene for 100 lung cancer patients and 100 healthy controls. The results showed that lung cancer was inversely associated with the variation of UGT1A10 at nucleotide 693 (odds ratio [OR]: 0.276; 95% confidence interval [CI]: 0.097~0.787; p=0.011). The nucleotide changes of UGT1A7 at position -57, 33, and 622 showed significant correlation with position 387, 391, and 392 (r=0.52, p＜0.0001). Furthermore, we found that the risk of lung cancer had the higher level of frequency in haplotype of wild-type UGT1A10-693/variant UGT1A7-622 (OR: 8.77; 95% CI: 1.10~70.0; p=0.02). We did not detect any association between lung cancer and UGT1A7 polymorphisms in Taiwanese population. Nevertheless, this study demonstrated the novel findings that determination for nucleotide 693 of the UGT1A10 gene may be useful to identify individuals susceptible to lung cancer and take measures to prevent development of this disease.

並列關鍵字

Lung cancer ； UDP-glucuronosyltransferases ； genetic polymorphisms ； synergistic effects