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PIN1基因多态性与广西人群乙型肝炎病毒相关肝细胞癌易感性

PIN1 genetic polymorphisms and the susceptibility of HBV-related hepatocellular carcinoma in a Guangxi population.

作者信息

Huang Li, Mo Zhuning, Lao Xianjun, Zhang Xiaolian, Liu Yanqiong, Sui Jingzhe, Qin Xue, Li Shan

机构信息

Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China.

Department of Blood Transfusion, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region, China.

出版信息

Tumour Biol. 2016 May;37(5):6599-606. doi: 10.1007/s13277-015-4539-z. Epub 2015 Dec 7.

Abstract

Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) plays a critical role in different signaling pathways, cell cycle progression and proliferation, and gene expression, and it has been found to overexpress in many tumor tissues. Recently, researchers have found that PIN1 gene polymorphisms may alter the function of protein and be associated with the risk of cancer. The present study analyzed three common polymorphisms in promoter regions (rs2233678 and rs2233679) and in exon2 (rs2233682) of the PIN1 gene in 254 patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and 235 healthy controls in a Guangxi study population to determine whether any relationship exists between the polymorphisms and the risk of HBV-related HCC. The results revealed that the rs2233679 TT genotype was associated with increased risk of HCC with HBV infection [odds ratio (OR) = 2.04, 95 % confidence interval (95 % CI) = 1.13-3.69, p = 0.019]. This association was stronger in men than in women (OR = 2.17, 95 % CI = 1.09-4.34, p = 0.028) as well as in men 50 years of age and older (OR = 3.91, 95 % CI = 1.29-11.80, p = 0.016); moreover, for alcohol drinkers, being a carrier of the PIN1 rs2233679 CT genotype had a moderately increased risk of HCC (OR = 3.98, 95 % CI = 1.02-15.57, p = 0.047). In contrast, people carrying the rs2233682 GA genotype and A alleles were 0.23 times more likely to develop HCC (OR = 0.23, 95 % CI = 0.06-0.87, p = 0.031 and OR = 0.23, 95 % CI = 0.06-0.87, p = 0.030). No such associations were found in the PIN1 rs2233678 polymorphisms between the HBV-related HCC cases and the controls. In addition, the haplotype GCA was found to be a high protection factor for HCC with HBV infection (OR = 0.14, 95 % CI = 0.03-0.62, p = 0.003). In conclusion, this study's findings suggest that the PIN1 rs2233679 TT genotype, the rs2233682GA genotype, and A alleles might be associated with the HBV-related HCC in a Guangxi study population.

摘要

肽基脯氨酰顺反异构酶NIMA相互作用蛋白1(PIN1)在不同的信号通路、细胞周期进程与增殖以及基因表达中发挥着关键作用,并且已发现在许多肿瘤组织中呈过表达。最近,研究人员发现PIN1基因多态性可能会改变蛋白质的功能,并与癌症风险相关。本研究在广西的研究人群中,分析了254例乙型肝炎病毒(HBV)相关肝细胞癌(HCC)患者和235例健康对照者中PIN1基因启动子区域(rs2233678和rs2233679)以及外显子2(rs2233682)中的三种常见多态性,以确定这些多态性与HBV相关HCC风险之间是否存在任何关联。结果显示,rs2233679 TT基因型与HBV感染导致的HCC风险增加相关[比值比(OR)=2.04,95%置信区间(95%CI)=1.13 - 3.69,p = 0.019]。这种关联在男性中比在女性中更强(OR = 2.17,95%CI = 1.09 - 4.34,p = 0.028),在50岁及以上男性中也更强(OR = 3.91,95%CI = 1.29 - 11.80,p = 0.016);此外,对于饮酒者而言,作为PIN1 rs2233679 CT基因型携带者患HCC的风险适度增加(OR = 3.98,95%CI = 1.02 - 15.57,p = 0.047)。相反,携带rs2233682 GA基因型和A等位基因的人患HCC的可能性降低0.23倍(OR = 0.23,95%CI = 0.06 - 0.87,p = 0.031以及OR = 0.23,95%CI = 0.06 - 0.87,p = 0.030)。在HBV相关HCC病例与对照者之间的PIN1 rs2233678多态性中未发现此类关联。此外,单倍型GCA被发现是HBV感染导致HCC的高保护因子(OR = 0.14,95%CI = 0.03 - 0.62,p = 0.003)。总之,本研究结果表明,在广西研究人群中,PIN1 rs2233679 TT基因型、rs2233682 GA基因型和A等位基因可能与HBV相关HCC有关。

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