EGFR基因多态性对局部晚期宫颈癌术后化疗患者临床疗效的影响
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摘要
目的探讨局部晚期宫颈癌患者表皮生长因子受体(EGFR)基因多态性对术后化疗效果的影响。方法选取局部晚期宫颈癌患者132例,所有患者手术治疗后均接受化疗。应用聚合酶链反应-连接酶反应检测EGFR基因型,根据EGFR基因型不同,将患者分为G/G基因型组(n=28)、G/A基因型组(n=70)、A/A基因型组(n=34)。比较3组患者化疗后的复发情况、病死情况及化疗期间不良反应发生情况,并对局部晚期宫颈癌患者化疗后复发的影响因素进行分析。结果 3组患者的化疗后1年复发率比较,差异无统计学意义(P﹥0.05);3组患者的化疗后2年复发率比较,差异有统计学意义(P﹤0.05),其中G/A基因型组和A/A基因型组患者的化疗后2年复发率均低于G/G基因型组(P﹤0.05)。3组患者的化疗后1年和化疗后2年病死率比较,差异均无统计学意义(P﹥0.05);化疗期间,3组患者消化道症状、神经毒性、中性粒细胞缺乏、血小板减少、转氨酶升高的发生率比较,差异均无统计学意义(P﹥0.05)。多因素Logistic回归分析显示,EGFR基因型为G/G型是局部晚期宫颈癌患者化疗后2年复发的独立危险因素(P=0.02)。结论 EGFR基因型为G/G型与局部进展期宫颈癌患者化疗后复发有关。
Objective To investigate the influence of single nucleotide polymorphisms of epidermal growth factor receptor(EGFR) on the clinical efficacy of postoperative chemotherapy in locally advanced cervical cancer. Method One hundred and thirty-two cases of locally advanced cervical cancer were selected, and all patients received chemotherapy after the operation. Polymerase chain reaction-ligase detection reaction was used to detect the gene type of EGFR. According to different EGFR genotypes, patients were divided into G/G genotype group(n=28), G/A genotype group(n=70) and A/A genotype group(n=34). The incidence of postchemotherapy recurrence, death and adverse reactions during chemotherapy in the three groups were compared, and the influencing factors of postchemotherapy recurrence in locally advanced cervical cancer patients were analyzed. Result There was not significant difference among three groups in 1-year recurrence rate after chemotherapy(P>0.05), and the differences among the three groups in 2-year recurrence rate after chemotherapy were significant(P<0.05). The 2-year recurrence rates after chemotherapy of patients with G/A and A/A genotype were both significantly lower than that of patients with G/G genotype(P<0.05). There was no statistically significant differences in 1-year or 2-year mortality after chemotherapy among three groups(P>0.05). During the chemotherapy,there was no statistically significant differences in the incidences of digestive symptoms, neurotoxicity, neutropenia,thrombocytopenia and transaminase elevation among the three groups(P>0.05). Multivariate Logistic regression analysis showed that G/G genotype of EGFR was an independent risk factor for recurrence in locally advanced cervical cancer after2 years of chemotherapy(P=0.02). Conclusion G/G genotype of EGFR is associated with postchemotherapy recurrence in locally advanced cervical cancer patients.
Objective To investigate the influence of single nucleotide polymorphisms of epidermal growth factor receptor(EGFR) on the clinical efficacy of postoperative chemotherapy in locally advanced cervical cancer. Method One hundred and thirty-two cases of locally advanced cervical cancer were selected, and all patients received chemotherapy after the operation. Polymerase chain reaction-ligase detection reaction was used to detect the gene type of EGFR. According to different EGFR genotypes, patients were divided into G/G genotype group(n=28), G/A genotype group(n=70) and A/A genotype group(n=34). The incidence of postchemotherapy recurrence, death and adverse reactions during chemotherapy in the three groups were compared, and the influencing factors of postchemotherapy recurrence in locally advanced cervical cancer patients were analyzed. Result There was not significant difference among three groups in 1-year recurrence rate after chemotherapy(P>0.05), and the differences among the three groups in 2-year recurrence rate after chemotherapy were significant(P<0.05). The 2-year recurrence rates after chemotherapy of patients with G/A and A/A genotype were both significantly lower than that of patients with G/G genotype(P<0.05). There was no statistically significant differences in 1-year or 2-year mortality after chemotherapy among three groups(P>0.05). During the chemotherapy,there was no statistically significant differences in the incidences of digestive symptoms, neurotoxicity, neutropenia,thrombocytopenia and transaminase elevation among the three groups(P>0.05). Multivariate Logistic regression analysis showed that G/G genotype of EGFR was an independent risk factor for recurrence in locally advanced cervical cancer after2 years of chemotherapy(P=0.02). Conclusion G/G genotype of EGFR is associated with postchemotherapy recurrence in locally advanced cervical cancer patients.
引文
[1] Moon EK, Oh CM, Won YJ, et al. Trends and age-periodcohort effects on the incidence and mortality rate of cervical cancer in Korea[J]. Cancer Res Treat, 2017, 49(2):526-533.
[2] Sousa AM, Teixeira CC, Medeiros SD, et al. Cervical cancer mortality in the state of Rio Grande do Norte, Brazil,1996-2010:time trends and projections up to 2030[J]. Epidemiol Serv Saude, 2016, 25(2):311-322.
[3] Deberne M, Levy A, Mondini M, et al. The combination of the antiviral agent cidofovir and anti-EGFR antibody cetuximab exerts an antiproliferative effect on HPV-positive cervical cancer cell lines’in-vitro and in-vivo xenografts[J].Anticancer Drugs, 2013, 24(6):599-608.
[4] Ma D, Hovey RL, Zhang Z, et al. Genetic variations in EGFR and ERBB4 increase susceptibility to cervical cancer[J].Gynecol Oncol, 2013, 131(2):445-450.
[5] Fukazawa EM, Baiocchi G, Soares FA, et al. Cox-2, EGFR,and ERBB-2 expression in cervical intraepithelial neoplasia and cervical cancer using an automated imaging system[J].Int J Gynecol Pathol, 2014, 33(3):225-234.
[6] Gladwish A, Milosevic M, Fyles A, et al. Association of apparent diffusion coefficient with disease recurrence in patients with locally advanced cervical cancer treated with radical chemotherapy and radiation therapy[J]. Radiology,2016, 279(1):158-166.
[7] Lee J, Lin JB, Chang CL, et al. Prophylactic lower para-aortic irradiation using intensity-modulated radiotherapy mitigates the risk of para-aortic recurrence in locally advanced cervical cancer:a 10-year institutional experience[J]. Gynecol Oncol, 2017, 146(1):20-26.
[8] Lee SW, Lee SH, Kim J, et al. Magnetic resonance imaging during definitive chemoradiotherapy can predict tumor recurrence and patient survival in locally advanced cervical cancer:a multi-institutional retrospective analysis of KROG16-01[J]. Gynecol Oncol, 2017, 147(2):334-339.
[9] Bandrés E, Barricarte R, Cantero C, et al. Epidermal growth factor receptor(EGFR)polymorphisms and survival in head and neck cancer patients[J]. Oral Oncol, 2007, 43(7):713-719.
[10] Lai CY, Sung FC, Hsieh LL, et al. Associations between genetic polymorphisms of epidermal growth factor receptor(EGFR)and survival of colorectal cancer(CRC)patients treated with 5-fluorouracil-based chemotherapy[J].Ann Surg Oncol, 2013, 20 Suppl 3:S599-S606.
[11] Schrevel M, Gorter A, Kolkman-Uljee SM, et al. Molecular mechanisms of epidermal growth factor receptor overexpression in patients with cervical cancer[J]. Mod Pathol,2011, 24(5):720-728.
[12] Subramanian PD, An Z, Yu JR, et al. Silencing of fused toes homolog enhances cisplatin sensitivity in cervical cancer cells by inhibiting epidermal growth factor receptormediated repair of DNA damage[J]. Cancer Chemother Pharmacol, 2016, 78(4):753-762.
[13]金鸽. EGFR基因单核苷酸多态性与宫颈癌放化疗近期疗效的相关性研究[D].石家庄:河北医科大学, 2012.
[14]樊晓妹,李魁秀,李琰,等. EGFR基因多态性与宫颈癌放化疗近期疗效的关系[J].实用妇产科杂志, 2014, 30(1):33-36.
[2] Sousa AM, Teixeira CC, Medeiros SD, et al. Cervical cancer mortality in the state of Rio Grande do Norte, Brazil,1996-2010:time trends and projections up to 2030[J]. Epidemiol Serv Saude, 2016, 25(2):311-322.
[3] Deberne M, Levy A, Mondini M, et al. The combination of the antiviral agent cidofovir and anti-EGFR antibody cetuximab exerts an antiproliferative effect on HPV-positive cervical cancer cell lines’in-vitro and in-vivo xenografts[J].Anticancer Drugs, 2013, 24(6):599-608.
[4] Ma D, Hovey RL, Zhang Z, et al. Genetic variations in EGFR and ERBB4 increase susceptibility to cervical cancer[J].Gynecol Oncol, 2013, 131(2):445-450.
[5] Fukazawa EM, Baiocchi G, Soares FA, et al. Cox-2, EGFR,and ERBB-2 expression in cervical intraepithelial neoplasia and cervical cancer using an automated imaging system[J].Int J Gynecol Pathol, 2014, 33(3):225-234.
[6] Gladwish A, Milosevic M, Fyles A, et al. Association of apparent diffusion coefficient with disease recurrence in patients with locally advanced cervical cancer treated with radical chemotherapy and radiation therapy[J]. Radiology,2016, 279(1):158-166.
[7] Lee J, Lin JB, Chang CL, et al. Prophylactic lower para-aortic irradiation using intensity-modulated radiotherapy mitigates the risk of para-aortic recurrence in locally advanced cervical cancer:a 10-year institutional experience[J]. Gynecol Oncol, 2017, 146(1):20-26.
[8] Lee SW, Lee SH, Kim J, et al. Magnetic resonance imaging during definitive chemoradiotherapy can predict tumor recurrence and patient survival in locally advanced cervical cancer:a multi-institutional retrospective analysis of KROG16-01[J]. Gynecol Oncol, 2017, 147(2):334-339.
[9] Bandrés E, Barricarte R, Cantero C, et al. Epidermal growth factor receptor(EGFR)polymorphisms and survival in head and neck cancer patients[J]. Oral Oncol, 2007, 43(7):713-719.
[10] Lai CY, Sung FC, Hsieh LL, et al. Associations between genetic polymorphisms of epidermal growth factor receptor(EGFR)and survival of colorectal cancer(CRC)patients treated with 5-fluorouracil-based chemotherapy[J].Ann Surg Oncol, 2013, 20 Suppl 3:S599-S606.
[11] Schrevel M, Gorter A, Kolkman-Uljee SM, et al. Molecular mechanisms of epidermal growth factor receptor overexpression in patients with cervical cancer[J]. Mod Pathol,2011, 24(5):720-728.
[12] Subramanian PD, An Z, Yu JR, et al. Silencing of fused toes homolog enhances cisplatin sensitivity in cervical cancer cells by inhibiting epidermal growth factor receptormediated repair of DNA damage[J]. Cancer Chemother Pharmacol, 2016, 78(4):753-762.
[13]金鸽. EGFR基因单核苷酸多态性与宫颈癌放化疗近期疗效的相关性研究[D].石家庄:河北医科大学, 2012.
[14]樊晓妹,李魁秀,李琰,等. EGFR基因多态性与宫颈癌放化疗近期疗效的关系[J].实用妇产科杂志, 2014, 30(1):33-36.