Association of XPD Asp312Asn polymorphism and response to oxaliplatin-based first-line chemotherapy and survival in patients with metastatic colorectal cancer

被引:7
作者
Liu, Zhuo [1 ]
Kong, Jiangyin [2 ]
Kong, Yuanyuan [2 ]
Cai, Feng [3 ]
Xu, Xiaocheng [4 ]
Liu, Jun [2 ]
Wang, Shihua [5 ]
机构
[1] Zhejiang Xiaoshan Hosp, Dept Internal Med, Hangzhou, Zhejiang, Peoples R China
[2] Zhejiang Xiaoshan Hosp, Dept Clin Lab, Hangzhou, Zhejiang, Peoples R China
[3] Zhejiang Xiaoshan Hosp, Canc Ctr, Hangzhou, Zhejiang, Peoples R China
[4] First Peoples Hosp Xiaoshan, Dept Oncol, Hangzhou, Zhejiang, Peoples R China
[5] Wake Forest Sch Med, Dept Canc Biol, Winston Salem, NC 27101 USA
来源
ADVANCES IN CLINICAL AND EXPERIMENTAL MEDICINE | 2019年 / 28卷 / 11期
关键词
colorectal cancer; polymorphism; oxaliplatin; survival; XPD; PHASE-III; THERAPY; REPAIR; RISK; MULTICENTER; TOXICITY; PREDICTS; ERCC1; GSTP1; ACID;
D O I
10.17219/acem/108552
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background. Identification of biomarkers predicting a response to chemotherapeutic drugs would greatly ease the selection of personalized therapy. The protein xeroderma pigmentosum group D (XPD) functions in nucleotide excision repair (NER) to remove DNA cross-links and in the regulation of transcription. The potential role of the Asp312Asn polymorphism in predicting the response to chemotherapy has not been established. Objectives. This prospective study was designed to determine the role of the XPD Asp312Asn polymorphism in predicting the response to oxaliplatin-based first-line chemotherapy and survival in patients with metastatic colorectal cancer. Material and methods. A total of 106 patients treated with 2 cycles of either FOLFOX4 (n = 72) or XELOX (n = 34) regimen as the chemotherapy were enrolled. The genotype of XPD Asp312Asn polymorphism was analyzed using TaqMan probe-based real-time polymerase chain reaction (PCR). Logistic regression was applied to predict the response to treatment protocols. Cox regression models were applied to predict overall survival. Results. The overall response to chemotherapy was 57.6% (61/106). FOLFOX4 and XELOX regimens demonstrated comparable efficacy. The XPD Asp312Asn polymorphism was not associated with the response to either FOLFOX4 or XELOX regimen in univariate and in multivariate logistic regression analyses. Levels of carcinoembryonic antigen (CEA) >= 5 ng/ml and female gender were associated with a lack of response to FOLFOX4, but not to XELOX regimen. In a multivariate survival analysis, XPD Asp312Asn AA genotype, lack of response to chemotherapy, CEA >= 5 ng/mL, and age >= 65 were significantly associated with worse overall survival. Conclusions. The XPD Asp312Asn polymorphism is associated with overall survival, but it is not a biomarker in predicting the response to oxaliplatin-based first-line chemotherapy in patients with metastatic colorectal cancer.
引用
收藏
页码:1459 / 1468
页数:10
相关论文
共 36 条
[1]   Colorectal Cancer Classification and Cell Heterogeneity: A Systems Oncology Approach [J].
Blanco-Calvo, Moises ;
Concha, Angel ;
Figueroa, Angelica ;
Garrido, Federico ;
Valladares-Ayerbes, Manuel .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2015, 16 (06) :13610-13632
[2]   A synonymous EGFR polymorphism predicting responsiveness to anti-EGFR therapy in metastatic colorectal cancer patients [J].
Bonin, Serena ;
Donada, Marisa ;
Bussolati, Gianni ;
Nardon, Ermanno ;
Annaratone, Laura ;
Pichler, Martin ;
Chiaravalli, Anna Maria ;
Capella, Carlo ;
Hoefler, Gerald ;
Stanta, Giorgio .
TUMOR BIOLOGY, 2016, 37 (06) :7295-7303
[3]   Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer [J].
Cassidy, Jim ;
Clarke, Stephen ;
Diaz-Rubio, Eduardo ;
Scheithauer, Werner ;
Figer, Arie ;
Wong, Ralph ;
Koski, Sheryl ;
Lichinitser, Mikhail ;
Yang, Tsai-Shen ;
Rivera, Fernando ;
Couture, Felix ;
Sirzen, Florin ;
Saltz, Leonard .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (12) :2006-2012
[4]  
Chang WS, 2016, ANTICANCER RES, V36, P1657
[5]   Mutations in the XPD helicase gene result in XP and TTD phenotypes, preventing interaction between XPD and the p44 subunit of TFIIH [J].
Coin, F ;
Marinoni, JC ;
Rodolfo, C ;
Fribourg, S ;
Pedrini, AM ;
Egly, JM .
NATURE GENETICS, 1998, 20 (02) :184-188
[6]   Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: A Multicenter study of the Gruppo Oncologico Dell'Italia Meridionale [J].
Colucci, G ;
Gebbia, V ;
Paoletti, G ;
Giuliani, F ;
Caruso, M ;
Gebbia, N ;
Carteni, G ;
Agostara, B ;
Pezzella, G ;
Manzione, L ;
Borsellino, N ;
Misino, A ;
Romito, S ;
Durini, E ;
Cordio, S ;
Di Seri, M ;
Lopez, M ;
Maiello, E .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (22) :4866-4875
[7]   Oxaliplatin plus high-dose folinic acid and 5-fluorouracil i.v. bolus (OXAFAFU) versus irinotecan plus high-dose folinic acid and 5-fluorouracil i.v. bolus (IRIFAFU) in patients with metastatic colorectal carcinoma: a Southern Italy Cooperative Oncology Group phase III trial [J].
Comella, P ;
Massidda, B ;
Filippelli, G ;
Palmeri, S ;
Natale, D ;
Farris, A ;
De Vita, F ;
Buzzi, F ;
Tafuto, S ;
Maiorino, L ;
Mancarella, S ;
Leo, S ;
Lorusso, V ;
De Lucia, L ;
Roselli, A .
ANNALS OF ONCOLOGY, 2005, 16 (06) :878-886
[8]   Molecular subtypes of metastatic colorectal cancer are associated with patient response to irinotecan-based therapies [J].
Del Rio, M. ;
Mollevi, C. ;
Bibeau, F. ;
Vie, N. ;
Selves, J. ;
Emile, J. -F. ;
Roger, P. ;
Gongora, C. ;
Robert, J. ;
Tubiana-Mathieu, N. ;
Ychou, M. ;
Martineau, P. .
EUROPEAN JOURNAL OF CANCER, 2017, 76 :68-75
[9]  
Duffy MJ, 2001, CLIN CHEM, V47, P624
[10]   Gene polymorphisms predict toxicity to neoadjuvant therapy in patients with rectal cancer [J].
Duldulao, Marjun P. ;
Lee, Wendy ;
Nelson, Rebecca A. ;
Ho, Joyce ;
Le, Maithao ;
Chen, Zhenbin ;
Li, Wenyan ;
Kim, Joseph ;
Garcia-Aguilar, Julio .
CANCER, 2013, 119 (05) :1106-1112