【摘要】：目的:探討TGFβ1信號通路基因TGFβ1、SMAD3及SMAD4的單核苷酸多態(tài)性與宮頸癌患者急性和慢性放射性直腸損傷的相關(guān)性及其臨床意義。方法:采用回顧性研究的方法,收集了121例接受過宮頸癌放射治療的患者,并隨訪他們發(fā)生放射性直腸損傷的情況。急性放射性直腸損傷按RTOG分級標(biāo)準(zhǔn),慢性放射性腸損傷按RTOG/EORTC分級標(biāo)準(zhǔn)。應(yīng)用第一代測序技術(shù)——雙脫氧鏈終止法檢測患者TGFβ1、SMAD3及SMAD4基因的單核苷酸多態(tài)性。采用SPSS18.0統(tǒng)計(jì)軟件,以單因素及多因素二元Logistic回歸分析的方法,統(tǒng)計(jì)TGFβ1(rs11466313,rs1800468,rs1800469,rs1800470,rs1800471)、SMAD3(rs12901499)及SMAD4(rs12456284)共7個位點(diǎn)的單核苷酸多態(tài)性與急性及慢性放射性直腸損傷的相關(guān)性。結(jié)果:SMAD4基因rs12456284位點(diǎn)多態(tài)性與慢性放射性直腸損傷的發(fā)生有顯著相關(guān)性。在多因素logistic回歸分析中,與AA基因型患者相比,AG基因型及GG基因型發(fā)生慢性腸炎的風(fēng)險明顯降低(OR=0.308,p=0.012及OR=0.121,p=0.007),但是與急性放射性直腸損傷無顯著相關(guān)性(p≥0.05)。而TGFβ1(rs11466313,rs1800468,rs1800469,rs1800470,rs1800471),SMAD3(rs12901499)的多態(tài)性與急性及慢性放射性直腸損傷均無明顯相關(guān)性(p≥0.05)。此外,放療總劑量≥85Gy也可顯著增加慢性放射性直腸損傷的發(fā)生風(fēng)險(OR=2.406,p=0.036)。結(jié)論:SMAD4基因rs12456284位點(diǎn)多態(tài)性與宮頸癌患者放療后慢性直腸損傷的發(fā)生相關(guān),其AG基因型及GG基因型可能是慢性放射性直腸損傷的保護(hù)性因素。放療總劑量≥85Gy是增加慢性放射性直腸損傷發(fā)生風(fēng)險的一個臨床因素。
[Abstract]:Objective: to investigate the association of single nucleotide polymorphisms (SNP) of TGF 尾 1 signaling gene TGF 尾 1 SMAD3 and SMAD4 with acute and chronic radiation-induced rectal injury in patients with cervical cancer and its clinical significance. Methods: 121 patients who received radiotherapy for cervical cancer were collected by retrospective study and followed up. Acute radiation-induced rectal injury was classified according to RTOG criteria and chronic radiation-induced intestinal injury was graded according to RTOG/EORTC criteria. The single nucleotide polymorphisms of TGF 尾 1 SMAD3 and SMAD4 gene were detected by the first generation sequencing technique. The single nucleotide polymorphisms (SMAD3 (rs12901499) and SMAD4 (rs12456284) of 7 loci of TGF 尾 1 (rs11466313, rs1800468, rs1800446 9, rs1800470) were analyzed by SPSS18.0 statistical software. The single nucleotide polymorphisms of SMAD3 (rs12901499) and SMAD4 (rs12456284) were correlated with acute and chronic radiation-induced rectal injury. Results the rs12456284 polymorphism of the SMAD4 gene was significantly associated with the occurrence of chronic radiation-induced rectal injury. In multivariate logistic regression analysis, the risk of chronic enteritis in patients with AG and GG genotype was significantly lower than that in patients with AA genotype (ORO 0.308, P 0.012 and ORX 0.121, P 0.007), but not significantly correlated with acute rectal radiation injury (p 鈮，

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