Carcinogen Metabolism Pathway and Tumor Suppressor Gene Polymorphisms and Gallbladder Cancer Risk in North Indians: A Hospital-Based Case-Control Study.
Carcinogen Metabolism Pathway and Tumor Suppressor Gene Polymorphisms and Gallbladder Cancer Risk in North Indians: A Hospital-Based Case-Control Study.
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DOI：
10.31557/apjcp.2019.20.12.3643
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发表时间：
2019-12-01
期刊：
影响因子：
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通讯作者：
Nakamura, Kazutoshi
中科院分区：
文献类型：
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作者：
Asai, Takao;Tsuchiya, Yasuo;Nakamura, Kazutoshi
背景：据报道，致癌物代谢途径和抑癌基因的多态性与胆囊癌的风险增加有关。然而，印度人的基因变异与胆囊癌风险之间的关联还没有得到很好的研究。我们研究了代谢酶细胞色素P450 1A1、谷胱甘肽S转移酶和肿瘤抑制基因P53的基因多态性是否与印度北部胆囊癌风险的增加有关。方法：这项基于医院的病例对照研究从2014年7月到2017年5月在印度勒克瑙的桑贾伊·甘地医学研究所进行了96例胆囊癌合并胆结石患者(病例)和93例胆石症患者(对照)的研究。使用简单的盐析法从每个患者的白细胞中提取基因组DNA。结果：采用TaqMan SNP基因分型方法检测了病例组和对照组的CYP1A1基因rs4646903、CYP1A1基因rs1048943和TP53基因rs1042522的基因频率，采用多重聚合酶链式反应分析了GSTM1和GSTT1基因的多态性。CC基因与北印度人患胆囊癌的风险增加相关(年龄和性别调整后的优势比为2.81；95%可信区间为1.19-6.61；P=0.02)。代谢途径基因多态的等位基因频率和等位基因频率在病例组和对照组之间无显著差异。结论：我们的数据提供了初步证据，TP53 rs1042522多态的CC基因型可能与北印度人患胆囊癌的风险增加有关。
BACKGROUND: Carcinogen metabolism pathway and tumor suppressor gene polymorphisms have been reported to be associated with increased gallbladder cancer risk. However, the association of genetic variants and gallbladder cancer risk in Indians are not well studied. We examined whether genetic polymorphisms of metabolic enzymes cytochrome P450 1A1 and glutathione S-transferase and tumor suppressor gene p53 (TP53) are associated with an increased risk of gallbladder cancer in North Indians.METHODS: This hospital-based case-control study was conducted in 96 gallbladder cancer patients with gallstones (cases) and 93 cholelithiasis patients (controls) at the Sanjay Gandhi Postgraduate Institute of Medical Sciences in Lucknow, India from July 2014 through May 2017. Genomic DNA was extracted from white blood cells of each patient using a simple salting-out procedure. The genotypic frequencies of CYP1A1 rs4646903, CYP1A1 rs1048943, and TP53 rs1042522 polymorphisms were investigated using TaqMan SNP Genotyping Assay and GSTM1 and GSTT1 polymorphisms were analyzed using the multiplex PCR assay.RESULTS: The frequency of CC genotype of TP53 rs1042522 polymorphism was 27.1% (26/96) in cases and 12.9% (12/93) in controls. The CC genotype was associated with an increased risk of gallbladder cancer in North Indians (age- and sex-adjusted odds ratio, 2.81; 95% confidence interval, 1.19-6.61; P = 0.02). No significant differences in genotypic and allelic frequencies of the metabolic pathway gene polymorphisms were found between cases and controls.CONCLUSIONS: Our data provide preliminary evidence that the CC genotype of the TP53 rs1042522 polymorphism may be associated with an increased risk of gallbladder cancer in North Indians.