目的:在本病例对照研究中,我们探索了遗传多态性在三个异源代谢基因中的作用,GSTM1,GSTT1和GSTP1,以及它们与北印度人群中胆囊癌(GBC)风险的关联。其病因受遗传影响,饮食习惯,生活方式,和环境因素。恒河带GBC发病率明显较高,印度。因此,我们通过该区域的基因-基因和基因-环境相互作用,探讨了GBC易感性的预后因素。
方法:分析了来自卡马拉尼赫鲁纪念肿瘤医院的108例GBC患者的遗传多态性,Prayagraj和142个匹配的控件。通过多重PCR方法分析GSTM1和GSTT1基因型,同时进行限制性片段长度多态性(RFLP)分析GSTP1基因型。采用Logistic回归分析计算比值比(OR)和95%置信区间(CI)分析GBC风险。
结果:GSTT1(空)基因型具有明显较高的GBC风险和易感(OR=2.044,CI=1.225-3.411,P=0.006),而GSTM1和GSTP1基因型与GBC风险没有任何关联。性别分层后,与男性相比,诊断为GBC的女性具有更高的GSTT1(null)基因型(OR=2.754,CI=1.428-5.310,P=0.003)。居住在农村地区的GBC患者的GSTT1(null)基因型较高,GBC风险为2倍(OR=2.031,CI=1.200-3.439,P=0.008)。Further,腺癌组织病理学的GBC患者也表现出更高的GSTT1(null)基因型(OR=2.113,CI=1.248-3.578,P=0.005)。GSTT1(非空)/GSTP1(Ile/Val+Val/Val)之间的基因-基因相互作用,增加GBC风险(OR=1.840,CI=1.135-2.982,P=0.013)。
结论:本研究表明,GSTT1(空)基因型在北印度人群中对GBC具有更高的易感性和风险。女性患者,腺癌组织病理学患者和农村居住GBC患者具有较高的GSTT1(空)基因型,可能有发生GBC的风险.基因型组合GSTT1(非空)/GSTP1(Ile/ValVal/Val)增加了GBC的易感性,可能被认为是北印第安人GBC的“风险”基因型。
OBJECTIVE: In the present
case-controlled study, we explored the role of genetic polymorphism in three xenobiotic metabolizing genes, GSTM1, GSTT1 and GSTP1, and their association to gallbladder cancer (GBC) risk in a North Indian population. Its etiology is influenced by genetic, food habits, lifestyle, and environmental factors. GBC incidence is significantly higher in the Gangetic belt, India. Therefore, we explored the prognostic factors in the susceptibility of GBC through gene-gene and gene-environment interaction in this region.
METHODS: Genetic polymorphism was analyzed in 108 GBC patients from Kamala Nehru Memorial Cancer Hospital, Prayagraj and 142 matched controls. GSTM1 and GSTT1 genotypes were analyzed by multiplex PCR method, while restriction fragment length polymorphism (RFLP) was performed to analyze GSTP1 genotypes. Logistic regression analysis calculating the odds ratio (OR) and 95% confidence interval (CI) was performed to analyze the GBC risk.
RESULTS: GSTT1 (null) genotype was at a significantly higher risk and susceptible to GBC (OR = 2.044, CI = 1.225-3.411, P = 0.006), while GSTM1 and GSTP1 genotypes did not show any association to GBC risk. After sex stratification, females diagnosed with GBC had higher GSTT1 (null) genotype (OR = 2.754, CI = 1.428-5.310, P = 0.003) compared to males. GBC patients dwelling in rural areas show higher GSTT1 (null) genotype with two-fold GBC risk (OR = 2.031, CI = 1.200-3.439, P = 0.008). Further, GBC patients with histopathology of adenocarcinoma also showed higher GSTT1 (null) genotype (OR = 2.113, CI = 1.248-3.578, P = 0.005). Gene-gene interaction between GSTT1 (non-null)/GSTP1 (Ile/Val + Val/Val), enhance the GBC risk (OR = 1.840, CI = 1.135-2.982, P = 0.013).
CONCLUSIONS: The present study suggests that GSTT1 (null) genotype has higher susceptibility and risk towards GBC in North Indian population. Female patients, patients with histopathology of adenocarcinoma and rural dwelling GBC patients have higher GSTT1 (null) genotypes and may be at risk of developing GBC. The genotype combination GSTT1 (non-null)/GSTP1 (Ile/Val + Val/Val) has increased GBC susceptibility and may be considered as \'at risk\' genotypes for GBC in North Indians.