整合素αV基因多态位点rs11902171与肺癌易感性的关联研究
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摘要
目的:探究整合素αV(integrinαV,ITGAV)基因3’UT R区的单核苷酸多态位点(single nucleotide polymorphism,SNP)rs11902171(G/C)与中国人群肺癌遗传易感性的关系。方法 :采用病例-对照研究设计,随机选取481例肺癌患者和560例健康人群对照,收集外周血样本后抽提基因组DNA,用高分辨率熔解曲线(high resolution melting,HRM)方法对rs11902171(G/C)位点进行基因分型,采用SPSS 19.0软件对分型数据进行统计分析。结果 :rs11902171位点分型后得到GG和GC两种基因型。在对照组中的分布频率分别为GG基因型89.8%、GC基因型10.2%,在病例组中的分布频率分别为GG基因型80.2%、GC基因型19.8%,两组间的基因型分布频率差异有统计学意义(P<0.001),且GC基因型相对于GG基因型能显著增加中国人群的肺癌遗传易感性(OR=2.18,95%CI:1.53~3.12)。根据吸烟及饮酒等因素分层分析显示,GC基因型除了饮酒组外,在其他组(>或≤60岁年龄组;男性或女性组;非饮酒组;吸烟或非吸烟组)均能显著增加肺癌易感性(均P<0.05)。结论:ITGAV基因的SNP位点rs11902171(G/C)与中国人群肺癌遗传易感性具有显著的相关性。
Objective: To investigate the association of single nucleotide polymorphism(SNP) locus rs11902171(G/C) locatedin the 3' untranslated region of integrin αV(ITGAV) gene with the susceptibility of Chinese lung cancer. Methods: A case-control study was performed between 481 cases of lung cancer patients and 560 healthy control subjects selected randomly. Genomic DNA was extracted from these collected peripheral blood samples. The locus of rs11902171(G/C) was genotyped by high resolution melting(HRM) method, and the genotyping data was analysed by SPSS 19. 0 software. Results : Only two genotypes, GG and GC, were obtained of the locus of rs11902171(G/C) in this study. The distribution frequencies of GG and GC was 89.8% and 10.2% respectively in the case group. In the control group,the distribution frequencies of GG and GC was80.2% and 19.8% respectively. The distribution of genotype have significant difference between lung cancer patients and healthy controls(P<0.001). GC genotype significantly increased the susceptibility of lung cancer in Chinese people(OR=2.18,95% CI: 1.53-3.12). GC genotype was significantly increased susceptibility of lung cancerin the age >or ≤60 years group,male or female group, non-drinking group and smoking or non-smoking group(except for alcohol group) was found by stratification analysis according to smoking and drinking and other factors(P<0.05). Conclusion: The present date suggest that the SNP locus of rs11902171(G/C) in ITGAV gene was associated with the susceptibility of lung cancer in Chinese population.
Objective: To investigate the association of single nucleotide polymorphism(SNP) locus rs11902171(G/C) locatedin the 3' untranslated region of integrin αV(ITGAV) gene with the susceptibility of Chinese lung cancer. Methods: A case-control study was performed between 481 cases of lung cancer patients and 560 healthy control subjects selected randomly. Genomic DNA was extracted from these collected peripheral blood samples. The locus of rs11902171(G/C) was genotyped by high resolution melting(HRM) method, and the genotyping data was analysed by SPSS 19. 0 software. Results : Only two genotypes, GG and GC, were obtained of the locus of rs11902171(G/C) in this study. The distribution frequencies of GG and GC was 89.8% and 10.2% respectively in the case group. In the control group,the distribution frequencies of GG and GC was80.2% and 19.8% respectively. The distribution of genotype have significant difference between lung cancer patients and healthy controls(P<0.001). GC genotype significantly increased the susceptibility of lung cancer in Chinese people(OR=2.18,95% CI: 1.53-3.12). GC genotype was significantly increased susceptibility of lung cancerin the age >or ≤60 years group,male or female group, non-drinking group and smoking or non-smoking group(except for alcohol group) was found by stratification analysis according to smoking and drinking and other factors(P<0.05). Conclusion: The present date suggest that the SNP locus of rs11902171(G/C) in ITGAV gene was associated with the susceptibility of lung cancer in Chinese population.
引文
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[23]Scartozzi M,Loretelli C,Bearzi I,et al.Allele polymorphisms of tumor integrins correlate with peritoneal carcinosis capability of gastric cancer cells in radically resected patients[J].Ann Oncol,2011,22(4):897-902.
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[3]Pastor MD,Nogal A,Molina-Pinelo S,et al.Proteomic biomarkers in lung cancer[J].Clin Transl Oncol,2013,15(9):671-682.
[4]Plichart M,Empana JP,Lambert JC,et al.Single polymorphism nucleotide rs1333049 on chromosome 9p21 is associated with carotid plaques but not with common carotid intima-media thickness in older adults.A combined analysis of the Three-City and the EVA studies[J].Atherosclerosis,2012,222(1):187-190.
[5]He F,Yang R,Li XY,et al.Single nucleotide polymorphisms of the NF-κB and STAT3 signaling pathway genes predict lung cancer prognosis in a Chinese Han population[J].Cancer Genet,2015,208(6):310-318.
[6]Campbell ID,Humphries MJ.Integrin structure,activation,and interactions[J].Cold Spring Harb Perspect Biol,2011,3(3):pii:a004994.
[7]Legate KR,Wickstr觟m SA,F覿ssler R.Genetic and cell biological analysis of integrin outside-in signaling[J].Genes Dev,2009,23(4):397-418.
[8]Xu GK,Yang C,Du J,et al.Integrin activation and internalization mediated by extracellular matrix elasticity:a biomechanical model[J].J Biomech,2014,47(6):1479-1484.
[9]Jean C,Gravelle P,Fournie JJ,et al.Influence of stress on extracellular matrix and integrin biology[J].Oncogene,2011,30(24):2697-2706.
[10]魻hlund D,Franklin O,Lundberg E,et al.Type IV collagen stimulates pancreatic cancer cell proliferation,migration,and inhibits apoptosis through an au tocrine loop[J].BMC Cancer,2013,13:154.
[11]Liu J,Huang J,He Y,et al.Genetic variants in the integrin gene predicted micro RNA-binding sites were associated with the risk of prostate cancer[J].Mol Carcinog,2014,53(4):280-285.
[12]Peer M,Stav D,Cyjon A,et al.Morbidity and mortality after major pulmonary resections in patients with locally advanced stage IIIA non-small cell lung carcinoma who underwent induction therapy[J].Heart Lung Circ,2015,24(1):69-76.
[13]Jia Y,Zang A,Shang Y,et al.Micro RNA-146a rs291-0164 polymorphism is associated with susceptibility to non-small cell lung cancer in the Chinese population[J].Med Oncol,2014,31(10):194.
[14]Ma XR,Cheng H,Wang XY,et al.Single-nucleotide polymorphisms of integrins are associated with the risk and lymph node metastasis of oral squamous cell carcinoma[J].Med Oncol,2012,29(4):2492-2498.
[15]Hsu A,Esmaeli B,Hayek B,et al.Analysis ofαv integrin protein expression in human eyelid and periorbital squamous cell carcinomas[J].J Cutan Pathol,2011,38(7):570-575.
[16]Lu JG,Li Y,Li L,et al.Overexpression of osteopontin and integrinαv in laryngeal and hypopharyngeal carcinomas associated with differentiation and metastasis[J].J Cancer Res Clin Oncol,2011,137(11):1613-1618.
[17]Wang H,Zhu Y,Zhao M,et al.mi RNA-29c suppresses lung cancer cell adhesion to extracellular matrix and metastasis by targeting integrinβ1 and matrix metalloproteinase2(MMP2)[J].PLo S One,2013,8(8):e70192.
[18]Jones J,Watt FM,Speight PM.Changes in the expression of alpha v integrins in oral squamous cell carcinomas[J].J Oral Pathol Med,1997,26(2):63-68.
[19]Zhang Y,Chen M,Venugopal S,et al.Isthmin exerts prosurvival and death-promoting effect on endothelial cells through alphavbeta5 integrin depending on its physical state[J].Cell Death Dis,2011,2:e153.
[20]Lin LJ,Grimme JM,Sun J,et al.The antagonistic roles of PDGF and integrinαvβ3 in regulating ROS production at focal adhesions[J].Biomaterials,2013,34(15):3807-3815.
[21]Yang GY,Guo S,Dong CY,et al.Integrinαvβ6 sustains and promotes tumor invasive growth in colon cancer progression[J].World J Gastroenterol,2015,21(24):7457-7467.
[22]Wang Y,Long L,Li T,et al.Polymorphisms of micro RNA-binding sites in integrin genes are associated with oral squamous cell carcinoma susceptibility and progression[J].Tohoku J Exp Med,2014,233(1):33-41.
[23]Scartozzi M,Loretelli C,Bearzi I,et al.Allele polymorphisms of tumor integrins correlate with peritoneal carcinosis capability of gastric cancer cells in radically resected patients[J].Ann Oncol,2011,22(4):897-902.