CYP1A1、CYP1A2、GSTM1和NAT2基因多态性与结直肠癌及吸烟的关联

Association of CYP1A1, CYP1A2, GSTM1 and NAT2 gene polymorphisms with colorectal cancer and smoking.

作者信息

Yoshida Kana, Osawa Kayo, Kasahara Mayumi, Miyaishi Aiko, Nakanishi Keiko, Hayamizu Saori, Osawa Yasunori, Tsutou Akimitsu, Tabuchi Yohiki, Shimada Etsuji, Tanaka Kenichi, Yamamoto Masahiro, Takahashi Juro

机构信息

Faculty of Health Sciences, Kobe University Graduate School of Medicine, 7-10-2 Tomogaoka, Sumaku, Kobe 654-0142, Japan.

出版信息

Asian Pac J Cancer Prev. 2007 Jul-Sep;8(3):438-44.

PMID:18159984

Abstract

We investigated CYP1A12A, CYP1A12C, CYP1A21C, CYP1A21F, GSTM1 and NAT2 gene polymorphisms, involving enzymes which metabolize many carcinogens, with reference to colorectal cancer risk. The distribution of these genotypes was not associated with risk overall. However, the CYP1A12A T/C genotype showed a significant association with colorectal cancer risk in never-smokers (odds ratio [OR], 3.06; 95% confidence interval [95% CI], 1.11-8.40; p = 0.030). The risk of the NAT2 rapid genotype in never-smokers was also statistically significantly increased (OR, 5.38; 95%CI, 1.80-16.1; p = 0.003). Furthermore, the joint effects of NAT2 rapid plus other genotypes were associated with colorectal cancer overall (OR, 3.12; 95%CI, 1.15-8.51; p = 0.026, for NAT2 rapid plus combined CYP1A12C Ile/Val and Val/Val, OR, 3.25; 95%CI, 1.09-9.74; p = 0.035, for NAT2 rapid plus CYP1A21C G/G, and OR, 4.20; 95%CI, 1.09-16.1; p = 0.037, for NAT2 rapid plus GSTM1 null, respectively). In never-smokers, the joint effects of NAT2 rapid plus other genotypes were remarkable (OR, 15.9; 95%CI, 1.87-135.8; p = 0.011, for NAT2 rapid plus combined CYP1A12A T/C and C/C, OR, 5.71; 95%CI, 1.49-21.9; p = 0.011, for NAT2 rapid plus combined CYP1A12C Ile/Val and Val/Val, and OR, 9.14; 95%CI, 2.05-40.7; p = 0.004, for NAT2 rapid plus CYP1A21F A/A, respectively). The joint effect of CYP1A21F A/A plus CYP1A21C G/G genotypes was also increased in never-smokers (OR, 6.16; 95%CI, 1.26-30.1; p = 0.025). Our findings suggest that the CYP1A12A T/C and NAT2 rapid genotypes is associated with colorectal cancer susceptibility without smoking exposure. These results also indicate that the NAT2 in combination with CYP1A12C, CYP1A21C, or GSTM1 genotypes may strongly confer susceptibility to colorectal cancer. In particular, the combination of NAT2 plus CYP1A12A, CYP1A12C, or CYP1A21F genotypes, and that of CYP1A21F plus CYP1A21C genotype may define a group of persons who are genetically susceptible to colorectal cancer in never smokers.

摘要

我们研究了CYP1A12A、CYP1A12C、CYP1A21C、CYP1A21F、GSTM1和NAT2基因多态性，这些基因涉及多种致癌物的代谢酶，以探讨其与结直肠癌风险的关系。这些基因型的分布总体上与风险无关。然而，CYP1A12A T/C基因型在从不吸烟者中与结直肠癌风险显示出显著关联（优势比[OR]，3.06；95%置信区间[95%CI]，1.11 - 8.40；p = 0.030）。从不吸烟者中NAT2快速代谢基因型的风险在统计学上也显著增加（OR，5.38；95%CI，1.80 - 16.1；p = 0.003）。此外，NAT2快速代谢基因型与其他基因型的联合作用总体上与结直肠癌相关（对于NAT2快速代谢基因型加CYP1A12C Ile/Val和Val/Val联合基因型，OR，3.25；95%CI，1.09 - 9.74；p = 0.035；对于NAT2快速代谢基因型加CYP1A21C G/G，OR，4.20；95%CI，1.09 - 16.1；p = 0.037；对于NAT2快速代谢基因型加GSTM1缺失基因型，分别为OR，3.12；95%CI，1.15 - 8.51；p = 0.026）。在从不吸烟者中，NAT2快速代谢基因型与其他基因型的联合作用显著（对于NAT2快速代谢基因型加CYP1A12A T/C和C/C联合基因型，OR，15.9；95%CI，1.87 - 135.8；p = 0.011；对于NAT2快速代谢基因型加CYP1A12C Ile/Val和Val/Val联合基因型，OR，5.71；95%CI，1.49 - 21.9；p = 0.011；对于NAT2快速代谢基因型加CYP1A21F A/A，OR，9.14；95%CI，2.05 - 40.7；p = 0.004）。从不吸烟者中CYP1A21F A/A加CYP1A21C G/G基因型的联合作用也增加（OR，6.16；95%CI，1.26 - 30.1；p = 0.025）。我们的研究结果表明，CYP1A12A T/C和NAT2快速代谢基因型与无吸烟暴露情况下的结直肠癌易感性相关。这些结果还表明，NAT2与CYP1A12C、CYP1A21C或GSTM1基因型的组合可能强烈赋予结直肠癌易感性。特别是，NAT2加CYP1A12A、CYP1A12C或CYP1A21F基因型的组合，以及CYP1A21F加CYP1A21C基因型的组合可能定义了一组从不吸烟者中对结直肠癌具有遗传易感性的人群。