代谢酶基因多态性与结直肠癌风险关联的病例对照研究

[A case-control study on the association between genetic polymorphisms of metabolic enzymes and the risk of colorectal cancer].

作者信息

Chen Kun, Jin Ming-juan, Fan Chun-hong, Song Liang, Jiang Qin-ting, Yu Wei-ping, Ma Xin-yuan, Yao Kai-yan

机构信息

Departent of Epidemiology and Health Statistics, Zhejiang University School of Public Health, Hangzhou 310031, China.

出版信息

Zhonghua Liu Xing Bing Xue Za Zhi. 2005 Sep;26(9):659-64.

PMID:16471212

Abstract

OBJECTIVE

To investigate the association between metabolic enzymes polymorphisms and the risk of colorectal cancer(CRC).

METHODS

Methods of detection used were based on polymerase chain reaction(PCR) including PCR-restriction fragment length polymorphism (PCR-RFLP), allele specific-PCR (AS-PCR) and multiple-PCR to identify the polymorphisms of CYP1A1 6235T/C, CYP1A2 734C/A, CYP2E1 -1259G/C, CYP2E1 -1019C/T, GSTM1 and T1 null type, NAT1 and NAT2 alleles among 140 cases and 343 cancer-free controls.

RESULTS

The allele frequencies of CYP1A1 6235C, CYP1A2 734A, CYP2E1 -1259C, CYP2E1 -1019T, GSTM1 and T1 null type, NAT1* 10 and NAT2 Mx (x = 1,2,3) alleles were 31.65%, 63.77%, 23.02%, 32.61%, 57.25%, 17.39%, 26.45% and 39.21% in the case group and 39.85%, 66.62%, 20.27%, 28.61%, 55.46%, 20.35%, 25.22% and 39.36% in control group, respectively. The frequencies were in Hardy-Weinberg equilibrium. Data on single genetic polymorphism and stratification analysis of multi-genetic polymorphisms indicated that CYP1A1 6235CC homozygote was associated with the significant reduction of CRC risk (OR = 0.79, 95% CI: 0.63-0.99) and in individuals with CYP1A2 734A allele. CYP1A1 62345C allele had the same effect (OR = 0.53, 95% CI: 0.34-0.83). However, individuals with GSTT1 null genotype, GSTM1 null genotype could significantly increase the risk (OR = 4.41, 95% CI: 1.21-16.10).

CONCLUSION

CYP1A1 6235C allele might play an important role in fighting against colorectal carcinogenesis. However, GSTM1 and T1 null genotype might serve as risk factors genetically. Larger scale population-based studies were needed to confirm the current findings.

摘要

目的

探讨代谢酶多态性与结直肠癌（CRC）风险之间的关联。

方法

采用基于聚合酶链反应（PCR）的检测方法，包括PCR-限制性片段长度多态性（PCR-RFLP）、等位基因特异性PCR（AS-PCR）和多重PCR，以鉴定140例病例和343例无癌对照中CYP1A1 6235T/C、CYP1A2 734C/A、CYP2E1 -1259G/C、CYP2E1 -1019C/T、GSTM1和T1无效型、NAT1和NAT2等位基因的多态性。

结果

病例组中CYP1A1 6235C、CYP1A2 734A、CYP2E1 -1259C、CYP2E1 -1019T、GSTM1和T1无效型、NAT1*10和NAT2 Mx（x = 1,2,3）等位基因的频率分别为31.65%、63.77%、23.02%、32.61%、57.25%、17.39%、26.45%和39.21%，对照组中分别为39.85%、66.62%、20.27%、28.61%、55.46%、20.35%、25.22%和39.36%。这些频率处于哈迪-温伯格平衡。单基因多态性数据和多基因多态性分层分析表明，CYP1A1 6235CC纯合子与CRC风险显著降低相关（OR = 0.79，95%CI：0.63 - 0.99），且在具有CYP1A2 734A等位基因的个体中也是如此。CYP1A1 62345C等位基因有相同作用（OR = 0.53，95%CI：0.34 - 0.83）。然而，具有GSTT1无效基因型、GSTM1无效基因型的个体可显著增加风险（OR = 4.41，95%CI：1.21 - 16.10）。