代谢酶基因多态性与结直肠癌的易感性

Association between genetic polymorphisms of metabolic enzymes and susceptibility of colorectal cancer

目的研究代谢酶细胞色素P450（cytochrome P450s，CYP）1A1、谷胱甘肽转移酶（glutathione—S-transferase，GST）M1和T1、尿苷二磷酸葡萄糖醛酸转移酶（UDPglucumnosyltransferase，UGT）1A7基因多态性与结直肠癌的易感性及其交互作用。方法2002年5月在浙江省嘉善县开展的现场病例对照研究及单纯病例研究，获得140例结直肠癌患者和343名健康对照，用PCR-限制性片段长度多态性等方法检测CYP1A1、GSTM1、GSTT1和UGT1A7的基因多态，并应用非条件logistic回归方法进行数据分析。结果CYPIA1 MspI多态（非编码区T6235C）C／C基因型、T／C和C／C基因型者相对于T／T基因型者的OR值分别为0．493（95％CI：0．254—0．956）和0．638（95％CI：0．427—0．952），具有统计学意义；GSTM1、GSTT1非缺陷型与缺陷型的分布频率对照组和病例组比较差异无统计学意义；对照组和病例组UGT1A7变异／变异型基因与野生纯合型基因比较差异有统计学意义（OR=2．501，95％CI：1．456—4．296）。单纯病例研究分析，CYP1A1与GSTT1、GSTM1与GSTT1对结直肠癌的发生存在交互作用，COR值分别为2．617（95％CI：1．015—6．752）和3．935（95％CI：1．323—11．706）；而CYPlAl与GSTM1、CYP1A1与UGT1A7之间无交互作用。结论CYP1A1 MspI变异型可降低机体对结直肠癌的易感性，而UGT1A7的变异／变异基因型可增加结直肠癌的罹患风险，CYP1A1与GSTT1、GSTM1与GSTT1对结直肠癌的发生存在交互作用。

Objective To investigate the association between CYP1A1, GSTM1, T1, UGT1A7 polymorphisms and colorectal cancer risk. Methods A case-control study of 140 patients with eaneers 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 reaetion-restrietion fragment length polymorphism （PCR-RFLP） and unconditional logistie regression was adopted to analyze the data. Results The CC, TC and CC genotypes of CYP1A1 T6235C significantly decreased the coloreetal eaneer risk as eompared to ＇IT genotype （OR =0. 493, 95% CI： 0. 254 -0. 956,OR =0. 638, 95% CI： 0. 427 -0. 952） . GSTM1 and GSTY1 null genotype had no significant association with the increased risk of colorectal eancer while the mutant variants of UGT1A7 might increase the risk of eoloreetal eaneer signifieantly （ OR = 2. 501, 95% CI： 1. 456 - 4. 296）. The CORvalue for the gene-gene interactions between CYP1A1 variant and the null genotype of GSTI＇I, GSTMl-deleted and GSTYl-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）, respeetively. There was no significant interaction between CYP1A1 and GSTM1, CYP1A1 and UGT1A7. Conclusion This study suggests that CYPIA1 and UGT1A7 variants might be assoeiated with eolorectal eancer. CYP1A1 and GSTM1 might interact on GSTY1 to influence the risk of colorectal cancer.