致發大腸直腸癌之基因多形性與環境因素

包括飲食及生活型態等環境因子在大腸直腸癌的發生上扮演重要的角色，遺傳性和偶發性大腸直腸癌基因的調控途徑已經在近10年被廣泛研究。例如高外顯率的錯誤配對修補基因突變即為導致遺傳性大腸直腸癌的重要因素，而常見的低外顯率代謝酵素和DNA修補酵素之多形性則可能是引起偶發性大腸直腸癌的主要因素。基因多形性會影響個體對環境物質中造成DNA傷害者的反應，因此，評估多形性基因的影響及其與環境因子間的交互作用能夠辨別易感受性族群，同時更能闡明偶發性大腸直腸癌的病因。本文獻探討針對大腸直腸癌的研究，就有關基因與環境因子交互作用的部分作一綜論，特別對近10年代謝酵素（包括細胞色素P450 1A1、細胞色素P450 1A2、麩氨醯硫轉移酵素及乙醯轉移酵素）和DNA修補酵素等基因多形性與大腸直腸癌相關之研究文獻，進行一簡要之整理，並探討未來具有希望的研究方向以及這些研究的限制。

關鍵字

大腸直腸癌；環境因子；基因多形性

並列摘要

Environmental factors, including dietary and lifestyle factors, play an important role in the etiology of colorectal cancer. Advances in technology for gene analysis have generated many opportunities to elucidate genetic pathways of hereditary and sporadic colorectal cancer in the last decade. Highly penetrant mutations in certain genes, such as mismatch repair genes, play a major role in the development of hereditary colorectal cancer, while low penetrant polymorphisms play a role in metabolizing and DNA repair enzymes. Because these mutation are common, they may contribute to a large proportion of sporadic colorectal cancer. Since genetic polymorphisms may modulate an individual's response to DNA-damaging agents derived from the environment, evaluating the impact of these polymorphic genes and their interactions with environmental factors may enable us to identify susceptible subgroups and better characterize the etiology of sporadic colorectal cancer. In this review we summarize the current studies regarding the role of gene-environment interactions in the development of colorectal cancer, including genetic polymorphisms of metabolic enzymes (cytochrome P4501A1, cytochrome P4501A2, N-acetyltransferase and glutathione S-transferase) and DNA repair enzymes. We also briefly discussed areas of particular promise for further study and the limitations of these studies.

並列關鍵字

Colorectal cancer ； Environmental factors ； Genetic polymorphisms

參考文獻

Aaltonen, L. A., Salovaara, R., Kristo, P.(1998).Incidence of Hereditary Nonpolyposis Colorectal Cancer and the Feasibility of Molecular Screening for the Disease.N Engl J Med.338

Google Scholar

Abdel-Rahman, S. Z., El-Zein, R. A.(2000).The 399Gln Polymorphism in the DNA Repair Gene XRCC1 Modulates the Genotoxic Response Induced in Human Lymphocytes by the Tobacco-Specific Nitrosamine NNK.Cancer Lett.159

Google Scholar

Abdel-Rahman, S. Z., Soliman, A. S., Bondy, M. L.(1999).Polymorphism of Glutathione S-Transferase Loci GSTM1 and GSTT1 and Susceptibility to Colorectal Cancer in Egypt.Cancer Lett.142

Google Scholar

Abdel-Rahman, S. Z., Soliman, A. S., Bondy, M. L.(2000).Inheritance of the 194Trp and the 399Gln Variant Alleles of the DNA Repair Gene XRCC1 are Associated with Increased Risk of Early-Onset Colorectal Carcinoma in Egypt.Cancer Lett.159

Google Scholar

Abernethy, D. R., Todd, E. L.(1985).Impairment of Caffeine Clearance by Chronic Use of Low-does Estrogen-Containing Oral Contraceptive.Eur J Clin Pharmacol.28

Google Scholar

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致發大腸直腸癌之基因多形性與環境因素

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