Toll样受体4基因多态性与前列腺癌易感性的相关性
|
摘要
目的:利用Meta分析的方法系统评价Toll样受体4基因(Toll-like receptor 4,TLR4)多态性(rs10759932、rs11536889和rs1927914)与前列腺癌(prostate cancer,PCa)发病风险的关系。方法:检索Pub Med、EMbase、Google学术、万方和中国知网数据库,语种不限,筛选出1960年1月1日至2016年6月10日符合纳入和排除标准的文献,应用STATA分析软件对各项研究进行异质性检验,计算合并OR值及其95%CI。结果:最终纳入6篇文献,包含3个位点12项病例-对照研究,计病例组和对照组分别为9 520和7 690例。对于rs11536889多态性位点,在隐性模型状态下,与前列腺癌发病显著相关(BB vs BA+AA:OR=0.247,95%CI:0.171~0.357;P=0.000)。然而对于rs10759932和rs1927914多态性位点在各比较模型下均与肿瘤无相关性。此外,对于rs1927914多态性位点,在以人种为分组依据的亚组分析中,可发现高加索人种与前列腺癌易感性显著相关(BB vs BA+AA:OR=0.538,95%CI:0.335~0.863;P=0.010)。结论:本研究证明TLR4基因rs11536889多态性位点与前列腺癌易感性相关,即rs11536889的BB基因型可能显著降低人群患前列腺癌的风险。
Objective: To systematically evaluate the relationship between TLR4 polymorphisms( rs10759932,rs11536889 and rs1927914) and prostate cancer( PCa) risk by Meta-analysis. Methods: Studies from January 1 st,1960 to June 10 th,2016 were retrieved through Pub Med,EMbase,Google Scholar,Wanfang and CNKI databases without language limitation to identify all of the eligible studies according to the inclusion and exclusion criteria to conduct the present Meta-analysis. The STATA software was applied to test the heterogeneity within studies,and calculated the OR values and 95% CI. Results: Finally,a total of six publications were collected comprising three polymorphisms including 12 case-control studies,encompassing 9 520 cases and 7 690 controls. We uncovered a significant association between rs11536889 polymorphism and PCa risk in recessive model( BB vs BA + AA: OR = 0. 247,95% CI:0. 171 ~ 0. 357,P = 0. 000). For rs10759932 and rs1927914 polymorphisms,no association was identified for PCa risk in all the genetic models. Nevertheless,for the rs1927914 polymorphism,in the subgroup analysis by ethnicity,we uncovered a significant association between Caucasian and PCa risk in recessive model( BB vs BA + AA: OR = 0. 538,95% CI: 0. 335 ~ 0. 863,P = 0. 010). Conclusion: The present work suggests that TLR4 rs11536889 polymorphism was associated with PCa risk,and that is to say,BB genotype of rs11536889 polymorphism can significantly decrease the risk of PCa in general population.
Objective: To systematically evaluate the relationship between TLR4 polymorphisms( rs10759932,rs11536889 and rs1927914) and prostate cancer( PCa) risk by Meta-analysis. Methods: Studies from January 1 st,1960 to June 10 th,2016 were retrieved through Pub Med,EMbase,Google Scholar,Wanfang and CNKI databases without language limitation to identify all of the eligible studies according to the inclusion and exclusion criteria to conduct the present Meta-analysis. The STATA software was applied to test the heterogeneity within studies,and calculated the OR values and 95% CI. Results: Finally,a total of six publications were collected comprising three polymorphisms including 12 case-control studies,encompassing 9 520 cases and 7 690 controls. We uncovered a significant association between rs11536889 polymorphism and PCa risk in recessive model( BB vs BA + AA: OR = 0. 247,95% CI:0. 171 ~ 0. 357,P = 0. 000). For rs10759932 and rs1927914 polymorphisms,no association was identified for PCa risk in all the genetic models. Nevertheless,for the rs1927914 polymorphism,in the subgroup analysis by ethnicity,we uncovered a significant association between Caucasian and PCa risk in recessive model( BB vs BA + AA: OR = 0. 538,95% CI: 0. 335 ~ 0. 863,P = 0. 010). Conclusion: The present work suggests that TLR4 rs11536889 polymorphism was associated with PCa risk,and that is to say,BB genotype of rs11536889 polymorphism can significantly decrease the risk of PCa in general population.
引文
[1]Miller KD,Siegel RL,Chun Chieh Lin,et al.Cancer treatment and survivorship statistics[J].CA Cancer J Clin,2016,66(4):271-289.
[2]Sperger JM,Strotman LN,Welsh A,et al.Integrated analysis of multiple biomarkers from circulating tumor cells enabled by exclusion-based analyte isolation[J].Clin Cancer Res,2016:1021.
[3]Ulz P,Belic J,Graf R,et al.Whole-genome plasma sequencing reveals focal amplifications as a driving force in metastatic prostate cancer[J].Nat Commun,2016,7:12008.
[4]Seisen T,Roupret M,Gomez F,et al.A comprehensive review of genomic landscape,biomarkers and treatment sequencing in castration-resistant prostate cancer[J].Cancer Treat Rev,2016,48:25-33.
[5]Coussens LM,Werb Z.Inflammation and cancer[J].Nature,2002,420:860-867.
[6]Wang X,Xu Z,Miao CH.Pooled analysis of association between a genetic variant in the 3'-untranslated region of Toll-like receptor4 and cancer risk[J].Genetics&Molecular Research,2015,14(4):17847-17855.
[7]Winchester DA,Gurel B,Till C,et al.Key genes involved in the immune response are generally not associated with intraprostatic inflammation in men without a prostate cancer diagnosis:Results from the prostate cancer prevention trial[J].Prostate,2016,76(6):565-574.
[8]Chen YC,Giovannucci E,Lazarus R,et al.Sequence variants of Toll-like receptor 4 and susceptibility to prostate cancer[J].Cancer Research,2005,65(24):11771-11778.
[9]Zheng SL,Augustsson-Balter K,Chang B,et al.Sequence variants of Toll-like receptor 4 are associated with prostate cancer risk:Results from the cancer prostate in Sweden study[J].Cancer Research,2004,64(8):2918-2922.
[10]Song J,Kim DY,Kim CS,et al.The association between Tolllike receptor 4(TLR4)polymorphisms and the risk of prostate cancer in Korean men[J].Cancer Genetics&Cytogenetics,2009,190(2):88-92.
[11]Shui IM,Stark JR,Penney KL,et al.Abstract 920:Genetic variation in the Toll-like receptor 4 and prostate cancer incidence and mortality[J].Prostate,2012,72(2):209-216.
[12]Cheng I,Plummer SJ,Casey G,et al.Toll-like receptor 4 genetic variation and advanced prostate cancer risk[J].Cancer Epidemiology,Biomarkers&Prevention,2007,16(2):352-355.
[13]Wang MH,Helzlsouer KJ,Smith MW.Association of IL10 and other immune response-and obesity-related genes with prostate cancer in CLUE II[J].Prostate,2009,69(8):874-885.
[14]Balistreri CR,Ccarruba C.A pilot study on prostate cancer risk and pro-inflammatory genotypes:Pathophysiology and therapeutic implications[J].Current Pharmaceutical Design,2010,16(6):718-724.
[15]Mantel N,Haenszel W.Statistical aspects of the analysis of data from retrospective studies of disease[J].J Natl Cancer Inst,1959,22(4):639-640.
[16]Dersimonian R,Nan L.Meta-analysis in clinical trials[J].Controlled Clinical Trials,1986,7(3):177-188.
[17]Hayashino Y,Noguchi Y,Fukui T.Systematic evaluation and comparison of statistical tests for publication bias[J].J Epidemiol,2005,15(6):235-243.
[18]Peters JL,Sutton AJ,Jones DR,et al.Comparison of two methods to detect publication bias in meta-analysis[J].Journal of the American Medical Association,2006,295(6):676-680.
[19]Andreani V,Gatti G,Simonella L,et al.Activation of Toll-like receptor 4 on tumor cells in vitro inhibits subsequent tumor growth in vivo[J].Cancer Research,2007,67(21):10519-10527.
[20]Wagenlehner FM,Elkahwaji JE,Algaba F,et al.The role of inflammation and infection in the pathogenesis of prostate carcinoma[J].BJU Int,2007,100(4):733-737.
[21]Cheng I,Plummer SJ,Casey G,et al.Toll-like receptor 4 genetic variation and advanced prostate cancer risk[J].Cancer Epidemiology Biomarkers&Prevention,2007,16(2):352-355.
[2]Sperger JM,Strotman LN,Welsh A,et al.Integrated analysis of multiple biomarkers from circulating tumor cells enabled by exclusion-based analyte isolation[J].Clin Cancer Res,2016:1021.
[3]Ulz P,Belic J,Graf R,et al.Whole-genome plasma sequencing reveals focal amplifications as a driving force in metastatic prostate cancer[J].Nat Commun,2016,7:12008.
[4]Seisen T,Roupret M,Gomez F,et al.A comprehensive review of genomic landscape,biomarkers and treatment sequencing in castration-resistant prostate cancer[J].Cancer Treat Rev,2016,48:25-33.
[5]Coussens LM,Werb Z.Inflammation and cancer[J].Nature,2002,420:860-867.
[6]Wang X,Xu Z,Miao CH.Pooled analysis of association between a genetic variant in the 3'-untranslated region of Toll-like receptor4 and cancer risk[J].Genetics&Molecular Research,2015,14(4):17847-17855.
[7]Winchester DA,Gurel B,Till C,et al.Key genes involved in the immune response are generally not associated with intraprostatic inflammation in men without a prostate cancer diagnosis:Results from the prostate cancer prevention trial[J].Prostate,2016,76(6):565-574.
[8]Chen YC,Giovannucci E,Lazarus R,et al.Sequence variants of Toll-like receptor 4 and susceptibility to prostate cancer[J].Cancer Research,2005,65(24):11771-11778.
[9]Zheng SL,Augustsson-Balter K,Chang B,et al.Sequence variants of Toll-like receptor 4 are associated with prostate cancer risk:Results from the cancer prostate in Sweden study[J].Cancer Research,2004,64(8):2918-2922.
[10]Song J,Kim DY,Kim CS,et al.The association between Tolllike receptor 4(TLR4)polymorphisms and the risk of prostate cancer in Korean men[J].Cancer Genetics&Cytogenetics,2009,190(2):88-92.
[11]Shui IM,Stark JR,Penney KL,et al.Abstract 920:Genetic variation in the Toll-like receptor 4 and prostate cancer incidence and mortality[J].Prostate,2012,72(2):209-216.
[12]Cheng I,Plummer SJ,Casey G,et al.Toll-like receptor 4 genetic variation and advanced prostate cancer risk[J].Cancer Epidemiology,Biomarkers&Prevention,2007,16(2):352-355.
[13]Wang MH,Helzlsouer KJ,Smith MW.Association of IL10 and other immune response-and obesity-related genes with prostate cancer in CLUE II[J].Prostate,2009,69(8):874-885.
[14]Balistreri CR,Ccarruba C.A pilot study on prostate cancer risk and pro-inflammatory genotypes:Pathophysiology and therapeutic implications[J].Current Pharmaceutical Design,2010,16(6):718-724.
[15]Mantel N,Haenszel W.Statistical aspects of the analysis of data from retrospective studies of disease[J].J Natl Cancer Inst,1959,22(4):639-640.
[16]Dersimonian R,Nan L.Meta-analysis in clinical trials[J].Controlled Clinical Trials,1986,7(3):177-188.
[17]Hayashino Y,Noguchi Y,Fukui T.Systematic evaluation and comparison of statistical tests for publication bias[J].J Epidemiol,2005,15(6):235-243.
[18]Peters JL,Sutton AJ,Jones DR,et al.Comparison of two methods to detect publication bias in meta-analysis[J].Journal of the American Medical Association,2006,295(6):676-680.
[19]Andreani V,Gatti G,Simonella L,et al.Activation of Toll-like receptor 4 on tumor cells in vitro inhibits subsequent tumor growth in vivo[J].Cancer Research,2007,67(21):10519-10527.
[20]Wagenlehner FM,Elkahwaji JE,Algaba F,et al.The role of inflammation and infection in the pathogenesis of prostate carcinoma[J].BJU Int,2007,100(4):733-737.
[21]Cheng I,Plummer SJ,Casey G,et al.Toll-like receptor 4 genetic variation and advanced prostate cancer risk[J].Cancer Epidemiology Biomarkers&Prevention,2007,16(2):352-355.