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代谢酶基因多态性与结直肠癌易感性的关联

[Association between genetic polymorphisms of metabolic enzymes and susceptibility of colorectal cancer].

作者信息

Fan Chun-hong, Jin Ming-juan, Zhang Yang, Song Liang, Xu Hong, Jiang Qin-ting, Yu Wei-ping, Chen Kun

机构信息

Department of Epidemiology, Zhejiang University School of Medicine, Hangzhou 310031, China.

出版信息

Zhonghua Yu Fang Yi Xue Za Zhi. 2006 Jan;40(1):13-7.

Abstract

OBJECTIVE

To investigate the association between CYP1A1, GSTM1, T1, UGT1A7 polymorphisms and colorectal cancer risk.

METHODS

A case-control study of 140 patients with cancers and 343 health controls was conducted to investigate the role of CYP1A1, GSTM1, T1, UGT1A7 polymorphisms in colorectal cancer. Gene-gene interactions among CYP1A1, GSTM1, T1, UGT1A7 polymorphisms were detected by case-control study and case-only study. Genotypes of four genes polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and unconditional logistic regression was adopted to analyze the data.

RESULTS

The CC, TC and CC genotypes of CYP1A1 T6235C significantly decreased the colorectal cancer risk as compared to TT genotype (OR = 0.493, 95% CI: 0.254-0.956, OR = 0.638, 95% CI: 0.427-0.952). GSTM1 and GSTT1 null genotype had no significant association with the increased risk of colorectal cancer while the mutant variants of UGT1A7 might increase the risk of colorectal cancer significantly (OR = 2.501, 95% CI: 1.456-4.296). The CORvalue for the gene-gene interactions between CYP1A1 variant and the null genotype of GSTT1, GSTM1-deleted and GSTT1-deleted genotype in the case-only design were 2.617 (95% CI: 1.015-6.752) and 3.935 (95% CI: 1.323-11.706), respectively. There was no significant interaction between CYP1A1 and GSTM1, CYP1A1 and UGT1A7.

CONCLUSION

This study suggests that CYP1A1 and UGT1A7 variants might be associated with colorectal cancer. CYP1A1 and GSTM1 might interact on GSTT1 to influence the risk of colorectal cancer.

摘要

目的

探讨细胞色素P450 1A1(CYP1A1)、谷胱甘肽S转移酶M1(GSTM1)、T1、尿苷二磷酸葡萄糖醛酸基转移酶1A7(UGT1A7)基因多态性与结直肠癌风险之间的关联。

方法

进行一项病例对照研究,纳入140例癌症患者和343名健康对照,以研究CYP1A1、GSTM1、T1、UGT1A7基因多态性在结直肠癌中的作用。通过病例对照研究和病例单组研究检测CYP1A1、GSTM1、T1、UGT1A7基因多态性之间的基因-基因相互作用。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析四个基因多态性的基因型,并采用非条件逻辑回归分析数据。

结果

与TT基因型相比,CYP1A1 T6235C的CC、TC和CC基因型显著降低了结直肠癌风险(比值比[OR]=0.493,95%置信区间[CI]:0.254-0.956;OR=0.638,95%CI:0.427-0.952)。GSTM1和GSTT1无效基因型与结直肠癌风险增加无显著关联,而UGT1A7的突变变体可能显著增加结直肠癌风险(OR=2.501,95%CI:1.456-4.296)。在病例单组设计中,CYP1A1变体与GSTT1无效基因型、GSTM1缺失和GSTT1缺失基因型之间的基因-基因相互作用的COR值分别为2.617(95%CI:1.015-6.752)和3.935(95%CI:1.323-11.706)。CYP1A1与GSTM1、CYP1A1与UGT1A7之间无显著相互作用。

结论

本研究提示CYP1A1和UGT1A7变体可能与结直肠癌有关。CYP1A1和GSTM1可能通过与GSTT1相互作用影响结直肠癌风险。

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