Nida Sadiq, Javid Bhat, Akbar Masood, Idrees Shah, Adil Wani, Ahmad Ganai Bashir
Department of Biochemistry, University of Kashmir, Hazratbal Srinagar, Jammu and Kashmir, India.
Department of Clinical Heamatology, Sher-e-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, Jammu and Kashmir, India.
Mol Biol Res Commun. 2017 Jun;6(2):77-84.
Studies on associations of various polymorphisms in xenobiotic metabolizing genes with different cancers including acute lymphoblastic leukaemia (ALL) are mixed and inconclusive. The current study analyzed the relationship between polymorphisms of phase I xenobiotic metabolizing enzymes, cytochromes P450 1A1 () and and childhood ALL in Kashmir, India. We recruited 200 confirmed ALL cases, and an equal number of controls, matched for sex, age and district of residence to the respective case. Information was obtained on various lifestyle and environmental factors in face to face interviews with the parents/attendants of each subject. Genotypes of and were analyzed by polymerase chain reaction and restriction fragment length polymorphism method. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Compared to the GG genotype, we found a higher ALL risk in subjects who harbored variant (AA) genotype (OR=20.9; 95% CI: 6.01-73.1, P<0.0001) and AG genotype (OR=42.6; 95% CI: 8.3-217.5, P<0.0001) of polymorphism. Although, we found a significant association of polymorphism with ALL risk, but the risk did not persist in the adjusted model (OR=6.76; 95% CI: 0.63-71.8, P=0.100). The study indicates that unlike , polymorphism is associated with ALL risk. However, more replicative studies with larger sample size are needed to substantiate our findings.
关于外源性物质代谢基因中的各种多态性与包括急性淋巴细胞白血病(ALL)在内的不同癌症之间关联的研究结果不一,尚无定论。本研究分析了I相外源性物质代谢酶细胞色素P450 1A1(CYP1A1)和CYP2E1的多态性与印度克什米尔地区儿童ALL之间的关系。我们招募了200例确诊的ALL病例,并选取了数量相等的对照,这些对照在性别、年龄和居住地区方面与相应病例相匹配。通过与每个受试者的父母/监护人进行面对面访谈,获取了各种生活方式和环境因素的信息。采用聚合酶链反应和限制性片段长度多态性方法分析CYP1A1和CYP2E1的基因型。使用逻辑回归模型计算比值比(OR)和95%置信区间(95%CI)。与GG基因型相比,我们发现携带CYP1A1多态性变异(AA)基因型(OR = 20.9;95%CI:6.01 - 73.1,P < 0.0001)和AG基因型(OR = 42.6;95%CI:8.3 - 217.5,P < 0.0001)的受试者患ALL的风险更高。虽然我们发现CYP2E1多态性与ALL风险存在显著关联,但在调整模型中该风险不再显著(OR = 6.76;95%CI:0.63 - 71.8,P = 0.100)。该研究表明,与CYP2E1不同,CYP1A1多态性与ALL风险相关。然而,需要更多样本量更大的重复性研究来证实我们的发现。