本文關(guān)鍵詞：XRCC1基因多態(tài)性與局部晚期直腸癌術(shù)前新輔助放化療敏感性的相關(guān)性研究　出處：《濟(jì)南大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

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【摘要】：背景新輔助放化療可以使局部晚期直腸癌患者的腫瘤體積縮小、提高根治性切除率及保留肛門的幾率,有效降低術(shù)后局部復(fù)發(fā)率,延長生存期。然而并非所有患者都能從新輔助放化療中受益。部分患者可能對新輔助放化療缺乏敏感性,不僅失去最佳手術(shù)機(jī)會,而且增加了經(jīng)濟(jì)負(fù)擔(dān)。因此,準(zhǔn)確地預(yù)測直腸癌患者對同步放化療的敏感性,不僅可以準(zhǔn)確地選擇局部晚期直腸癌患者的治療方案,而且可以減少患者的痛苦與經(jīng)濟(jì)負(fù)擔(dān)。人類x線交錯互補(bǔ)修復(fù)基因1(X-ray repair cross complementing gene1,XRCC1)的Arg399Gln多態(tài)性在涉及肺癌、食管癌的多項研究中顯示其與放化療敏感性的顯著性關(guān)系,可能是預(yù)測新輔助治療療效的生物學(xué)指標(biāo)。本研究中通過檢測XRCC1的Arg399Gln多態(tài)性在局部晚期直腸癌患者中的表達(dá)情況,分析其與新輔助放化療的敏感性之間有無顯著性關(guān)系,從而認(rèn)識和了解其在局部晚期直腸癌患者新輔助放化療療效預(yù)測中的意義。方法收集64例局部晚期直腸癌患者的一般臨床病理資料,并檢測XRCC1的Arg399Gln多態(tài)性�；颊咴诮邮苄螺o助放化療后行手術(shù)治療,通過CT療效評價及術(shù)后Dworak’s腫瘤退縮分級(Tumor Regression Grading,TRG)對患者的新輔助放化療敏感性進(jìn)行評價,單因素分析XRCC1 399位點多態(tài)性、患者臨床病理資料分別與新輔助放化療敏感性之間有無顯著性關(guān)聯(lián),并通過多因素logistic回歸分析找出其中的獨立影響因素,尋找可以預(yù)測直腸癌新輔助放化療療效的指標(biāo),以指導(dǎo)不同敏感性的局部晚期直腸癌患者進(jìn)行個體化治療。結(jié)果研究中共收集到局部晚期直腸癌患者(ct3-4n0m0或任何tn+m0)病例64例,其中男性患者38例,女性患者26例。所有64例患者采集外周血通過pcr-rflp技術(shù)獲得相應(yīng)基因型。其中純合子gg型患者33例,雜合子ga型患者24例,aa型患者7例�；蛐头植冀�(jīng)hardy-weinberg平衡檢驗發(fā)現(xiàn)存在群體基因遺傳平衡(p=0.42)。新輔助治療后ct療效評價顯示獲得cr的患者數(shù)為10例;pr患者數(shù)為16例;sd患者數(shù)為24例;獲得pd患者數(shù)為14例。術(shù)后病理按照dworak’s腫瘤退縮分級,其中trg4(pcr)者12例;trg3者17例;trg2患者15例;trg1者12例;trg0者8例。在以dworak’s腫瘤退縮分級為評價標(biāo)準(zhǔn)的新輔助治療敏感性研究中,通過單因素分析我們發(fā)現(xiàn):術(shù)前ct分期、cn分期以及患者的術(shù)前cea水平均與新輔助放化療的敏感性及療效顯著相關(guān),p值分別為0.002、0.016、0.047。xrcc1基因arg399gln多態(tài)性與局部晚期直腸癌患者的新輔助放化療敏感性顯著相關(guān)(p=0.011),攜帶野生型基因gg的患者對新輔助治療的敏感性顯著優(yōu)于攜帶ga和aa型患者。在ct為主的resist評價標(biāo)準(zhǔn)中,術(shù)前ct分期、cn分期、術(shù)前cea水平及xrcc1399位點多態(tài)性也均與新輔助治療敏感性顯著相關(guān)。在多因素logistic回歸分析中,我們發(fā)現(xiàn),患者術(shù)前ct分期(p=0.005)是影響直腸癌患者新輔助治療療效的獨立因素。在局部晚期直腸癌術(shù)前ct分期較低的情況下,xrcc1基因arg399gln位點無突變(gg型)的直腸癌患者經(jīng)新輔助治療后可以獲得更好的療效。結(jié)論術(shù)前ct分期、cn分期以及患者的術(shù)前cea水平與新輔助放化療的敏感性及療效顯著相關(guān)。xrcc1基因arg399gln多態(tài)性與局部晚期直腸癌患者的新輔助放化療敏感性顯著相關(guān),攜帶野生型基因gg的患者對新輔助治療的敏感性顯著優(yōu)于攜帶ga和aa型患者。術(shù)前ct分期為直腸癌患者新輔助治療療效的獨立影響因素。在局部晚期直腸癌術(shù)前ct分期較低的情況下,xrcc1基因arg399gln位點無突變(gg型)的直腸癌患者經(jīng)新輔助治療后可以獲得更好的療效。
[Abstract]:Background neoadjuvant chemoradiotherapy can reduce the volume of tumor in locally advanced rectal cancer, increase the rate of radical resection and preserve the anus, effectively reduce the local recurrence rate and prolong the survival time. Not all patients, however, can benefit from neoadjuvant chemoradiotherapy. Some patients may not be sensitive to neoadjuvant chemoradiotherapy, not only lose the best operation opportunity, but also increase the economic burden. Therefore, accurately predicting the sensitivity of rectal cancer patients to concurrent chemoradiotherapy can not only accurately select the treatment plan for locally advanced rectal cancer, but also reduce the pain and economic burden of patients. The human X-ray repair cross complementing gene 1 (X-ray repair cross complementing gene1, XRCC1) Arg399Gln polymorphism showed significant relationship with chemotherapy sensitivity in a number of studies involving lung cancer and esophageal cancer, may predict biological response to neoadjuvant therapy index. Expression of Arg399Gln polymorphisms detected by XRCC1 in this study in patients with locally advanced rectal cancer, there is no significant relationship between the analysis and the sensitivity of neoadjuvant chemotherapy, so as to know and understand the local advanced rectal cancer patients with neoadjuvant chemotherapy efficacy prediction of significance. Methods the general clinicopathological data of 64 patients with locally advanced rectal cancer were collected and the Arg399Gln polymorphism of XRCC1 was detected. In patients receiving neoadjuvant treatment chemotherapy followed by surgery, and postoperative curative effect evaluation by CT Dworak s (Tumor Regression Grading tumor regression grading, TRG) of patients treated with neoadjuvant chemoradiotherapy sensitivity evaluation, single factor analysis there is no significant correlation between XRCC1 399 polymorphism and clinical pathological data and the new adjuvant chemotherapy sensitivity, and by multivariate logistic regression analysis to identify independent factors which can predict for neoadjuvant chemoradiotherapy for rectal cancer curative effect, individualized treatment is to guide the different sensitivity of patients with locally advanced rectal cancer. Results a total of 64 cases of locally advanced rectal cancer (ct3-4n0m0 or any tn+m0) were collected, including 38 male patients and 26 female patients. The peripheral blood was collected from all 64 patients and the corresponding genotypes were obtained by PCR-RFLP technique. Among them, there were 33 patients with homozygote type GG, 24 heterozygote GA patients and 7 patients with type AA. Genetic balance (p=0.42) was found in the genotype distribution by Hardy-Weinberg balance test. After the new adjuvant treatment, the CT efficacy evaluation showed that the number of patients received CR was 10 cases, the number of PR patients was 16 cases, the number of SD patients was 24 cases, and the number of PD patients was 14 cases. The postoperative pathology was based on Dworak 's tumor regression classification, of which 12 cases were trg4 (PCR), 17 of trg3, 15 in trg2, 12 in TRG1 and 8 in trg0. In Dworak s' tumor regression as the evaluation criteria for the classification of neoadjuvant treatment sensitivity study, through single factor analysis we found that: there is a significant correlation between sensitivity and efficacy of preoperative CT staging, CN staging and preoperative CEA level were associated with neoadjuvant chemotherapy, P values were 0.002, 0.016, 0.047. The Arg399Gln polymorphism of XRCC1 gene is significantly correlated with the sensitivity of neoadjuvant chemoradiotherapy in locally advanced rectal cancer (p=0.011). The patients with wild type GG are more sensitive to neoadjuvant therapy than those with GA and AA. Among the CT based resist evaluation criteria, preoperative CT staging, CN stage, preoperative CEA level and xrcc1399 site polymorphism were also significantly associated with the sensitivity of neoadjuvant therapy. In the multifactor logistic regression analysis, we found that preoperative CT staging (p=0.005) was an independent factor affecting the efficacy of neoadjuvant therapy for rectal cancer. In patients with locally advanced rectal cancer with low CT stage before operation, the XRCC1 gene Arg399Gln site without mutation (GG type) of rectal cancer can get better results after neoadjuvant therapy. Conclusion the preoperative CT staging, CN staging and preoperative CEA levels of the patients were significantly related to the sensitivity and efficacy of neoadjuvant radiochemotherapy. The Arg399Gln polymorphism of XRCC1 gene is significantly correlated with the sensitivity of neoadjuvant chemoradiotherapy in locally advanced rectal cancer. The patients with wild type GG are more sensitive to neoadjuvant therapy than those carrying GA and AA. Preoperative CT staging is an independent factor in the efficacy of neoadjuvant therapy for rectal cancer. In patients with locally advanced rectal cancer with low CT stage before operation, the XRCC1 gene Arg399Gln site without mutation (GG type) of rectal cancer can get better results after neoadjuvant therapy.
【學(xué)位授予單位】：濟(jì)南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R735.37

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本文編號：1346019