背景:细胞色素P450(CYP)包含一组在异种生物代谢中很重要的I期代谢酶。已经全面研究了CYPs的遗传多态性与一系列疾病的关联。在这项研究中,我们评估了CYP1A的单核苷酸多态性(SNP),CYP1B,CYP2B,和CYP2C及其在马哈拉施特拉邦农村人口胃肠道(GI)癌症易感性中的作用。
方法:在以医院为基础的病例对照研究中,通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法研究了CYP基因多态性的相关性。研究对象包括200名临床证实的GI癌症患者和相同数量的健康对照。用95%置信区间(CI)和P值评估比值比(OR),找出关联水平,其中P≤0.005被认为具有统计学意义。
结果:对CYP1A1*2A(rs4646903)进行分析后,CYP1B1*3(rs1059836),CYP2B6*5(rs3211371),CYP2C8*2(rs11572103),CYP2C9*2(rs1799853),和CYP2C9*3(rs1057910),我们注意到CYP2B6*5的变异(T)等位基因在研究人群中具有显著升高的GI癌风险(OR=4.43;95%CI:2.20-8.90;P<0.0001)。CYP1B1*3的G/C杂合子等位基因的基因型分布(OR=0.19,95%CI=0.12-0.32;P<0.0001)和纯合变体C/C等位基因(OR=0.24,95%CI=0.13-0.45;P<0.0001)与胃肠道癌的发展呈负相关。
结论:这项研究的发现支持CYP2B6*5基因多态性可能参与了胃肠道肿瘤的发生发展。然而,CYP1A的其他SNP,CYP1B,和CYP2C基因并不表示在马哈拉施特拉邦农村地区的研究人群中发生胃肠道癌症的风险。
BACKGROUND: Cytochrome P450 (CYP) comprises a group of phase-I metabolizing enzymes that are important in xenobiotics metabolism. Genetic polymorphism of CYPs has been comprehensively studied for their association with a range of diseases. In this
study, we assessed single-nucleotide polymorphism (SNP) of CYP1A, CYP1B, CYP2B, and CYP2C and their role in gastrointestinal (GI) cancer susceptibility in the rural population of Maharashtra.
METHODS: In this hospital-based case-control
study, the association of polymorphism of CYP genes was studied by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The
study subjects included 200 clinically confirmed GI cancer patients and equal number of healthy controls. Odds ratio (OR) with 95% confidence interval (CI) and P value were evaluated to find out the level of association, where P ≤ 0.005 was considered statistically significant.
RESULTS: After the analysis of CYP1A1*2A (rs4646903), CYP1B1*3 (rs1059836), CYP2B6*5 (rs3211371), CYP2C8*2 (rs11572103), CYP2C9*2 (rs1799853), and CYP2C9*3 (rs1057910), we noticed that variant (T) allele of CYP2B6*5 possessed significantly elevated risk (OR = 4.43; 95% CI: 2.20-8.90; P < 0.0001) of GI cancer in studied population. The genotypic distribution of G/C heterozygote allele of CYP1B1*3 (OR = 0.19, 95% CI = 0.12-0.32; P < 0.0001) and homozygous variant C/C allele (OR = 0.24, 95% CI = 0.13-0.45; P < 0.0001) showed a negative association with the development of GI cancer.
CONCLUSIONS: The findings from this
study supported that polymorphism of CYP2B6*5gene may be involved in the development of GI cancer. However, other SNPs of CYP1A, CYP1B, and CYP2C genes did not signify the risk for GI cancer in the studied population of rural Maharashtra.