CYP1A1 and CYP2E1 genotypes and risk of esophageal squamous cell carcinoma in a high-incidence region, Kashmir
CYP1A1 and CYP2E1 genotypes and risk of esophageal squamous cell carcinoma in a high-incidence region, Kashmir
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DOI：
10.1007/s13277-014-1694-6
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发表时间：
2014-06-01
期刊：
影响因子：
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通讯作者：
Dar, Nazir Ahmad
中科院分区：
文献类型：
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作者：
Bhat, Gulzar Ahmad;Shah, Idrees Ayoub;Dar, Nazir Ahmad
该研究分析了I相外源性物质代谢酶细胞色素P450（CYP）1A 1和CYP 2 E1的遗传多态性与印度克什米尔食管鳞状细胞癌（ESCC）之间的关系。应用聚合酶链反应-限制性片段长度多态性技术，对526例食管鳞癌患者及相应对照组的CYP 1A 1和CYP 2 E1基因型进行分析。条件Logistic回归模型被用来评估各种基因型与ESCC、基因-基因和基因-环境相互作用的关系。携带CYP 1A 1瓦尔/瓦尔基因型的个体发生食管癌的危险性高（OR = 2.87; 95% CI = 1.00-8.44），同时携带CYP 2 E1基因型c1/c1的个体发生食管癌的危险性增加（OR = 5.68; 95% CI = 1.09-29.52）。当分析仅限于曾经吸烟者时，CYP 1A 1瓦尔/瓦尔基因型导致的风险进一步增加（OR = 8.55; 95% CI = 1.86-42.20）。CYP 2 E1 c1/c2基因型与食管鳞癌的发生呈负相关（OR = 0.27，95%CI = 0.17-0.43）。当CYP 1A 1 Ile/Ile也存在时，CYP 2 E1 c1/c2基因型保持负相关（OR = 0.18; 95% CI = 0.09-0.32），以及当分析仅限于曾经吸烟者时（OR = 0.45; 95% CI = 0.23-0.90）。CYP 1A 1（瓦尔/瓦尔）和CYP 2 E1（c1/c1）基因型之间存在显著的交互作用（OR = 1.30; 95% CI = 1.12-1.51; P = 0.001）; CYP 1A 1（瓦尔/瓦尔）与吸烟之间存在显著的交互作用（OR = 1.31; 95% CI = 1.01-1.69; P = 0.043）。该研究表明CYP 1A 1瓦尔/瓦尔和CYP 2 E1 c1/c1基因型与ESCC风险显着相关。
The study analyzed the relationship between genetic polymorphisms of phase I xenobiotic metabolizing enzymes, cytochromes P450 (CYP) 1A1 and CYP2E1 and esophageal squamous cell carcinoma (ESCC) in Kashmir, India. The different genotypes of CYP1A1 and CYP2E1 were analyzed by polymerase chain reaction and restriction fragment length polymorphism in 526 ESCC cases and equal number of matched controls. Conditional logistic regression models were used to assess the association of various genotypes with ESCC, gene-gene, and gene-environment interactions. High risk of ESCC was found in participants who carried CYP1A1 Val/Val genotype (OR = 2.87; 95 % CI = 1.00-8.44) and the risk increased in such individuals when c1/c1 of CYP2E1 genotype was also present (OR = 5.68; 95 % CI = 1.09-29.52). Risk due to CYP1A1 Val/Val genotype was further enhanced (OR = 8.55; 95 % CI = 1.86-42.20) when the analysis was limited to ever smokers. Participants who carried CYP2E1 c1/c2 genotype showed an inverse relation (OR = 0.27; 95 % CI = 0.17-0.43) with ESCC. The inverse association of CYP2E1 c1/c2 genotype was retained when CYP1A1 Ile/Ile was also present (OR = 0.18; 95 % CI = 0.09-0.32), as well as when analysis was limited to ever smokers (OR = 0.45; 95 % CI = 0.23-0.90). Significant interaction was found between CYP1A1 (Val/Val) and CYP2E1 (c1/c1) genotypes (OR = 1.30; 95 % CI = 1.12-1.51; P = 0.001) and between CYP1A1 (Val/Val) and smoking (OR = 1.31; 95 % CI = 1.01-1.69; P = 0.043). The study suggests CYP1A1 Val/Val and CYP2E1 c1/c1 genotypes are significantly associated with ESCC risk.