Department of Biochemistry, University of Allahabad, Prayagaj, UP, India.
Department of Radiation Oncology, Kamala Nehru Memorial Hospital, Prayagraj, UP, India.
J Cancer Res Ther. 2023 Oct 1;19(7):1908-1914. doi: 10.4103/jcrt.jcrt_1117_21. Epub 2023 Apr 26.
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.
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.
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).
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.
在本病例对照研究中，我们探讨了三种外源生物代谢基因 GSTM1、GSTT1 和 GSTP1 的遗传多态性及其与印度北部人群胆囊癌（GBC）风险的关系。其病因受遗传、饮食习惯、生活方式和环境因素的影响。GBC 在印度恒河平原的发病率明显较高。因此，我们通过该地区的基因-基因和基因-环境相互作用，探讨了 GBC 易感性的预后因素。
对来自 Prayagraj 的 Kamala Nehru Memorial Cancer Hospital 的 108 名 GBC 患者和 142 名匹配对照进行了遗传多态性分析。GSTM1 和 GSTT1 基因型采用多重 PCR 法分析，GSTP1 基因型采用限制性片段长度多态性（RFLP）分析。采用计算比值比（OR）和 95%置信区间（CI）的 logistic 回归分析来分析 GBC 风险。
GSTT1（缺失）基因型的风险显著增加，易患 GBC（OR=2.044，CI=1.225-3.411，P=0.006），而 GSTM1 和 GSTP1 基因型与 GBC 风险无关。进行性别分层后，与男性相比，女性 GBC 患者的 GSTT1（缺失）基因型更高（OR=2.754，CI=1.428-5.310，P=0.003）。居住在农村地区的 GBC 患者显示出更高的 GSTT1（缺失）基因型，GBC 风险增加两倍（OR=2.031，CI=1.200-3.439，P=0.008）。此外，具有腺癌组织病理学的 GBC 患者也表现出更高的 GSTT1（缺失）基因型（OR=2.113，CI=1.248-3.578，P=0.005）。GSTT1（非缺失）/GSTP1（Ile/Val+Val/Val）基因-基因相互作用增加了 GBC 的风险（OR=1.840，CI=1.135-2.982，P=0.013）。
本研究表明，GSTT1（缺失）基因型在印度北部人群中对 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地区的 GBC 患者具有更高的 GSTT1（缺失）基因型，可能有患 GBC 的风险。基因型组合 GSTT1（非缺失）/GSTP1（Ile/Val+Val/Val）增加了 GBC 的易感性，可被视为印度北部人群 GBC 的“高危”基因型。
