Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 11, November, p. 1459–1468

doi: 10.17219/acem/108552

Publication type: original article

Language: English

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

Zhuo Liu1,A,B,D,E,F, Jiangyin Kong2,B,F, Yuanyuan Kong2,B,E,F, Feng Cai3,B,E,F, Xiaocheng Xu4,B,E,F, Jun Liu2,A,B,E,F, Shihua Wang5,C,D,F

1 Department of Internal Medicine, Zhejiang Xiaoshan Hospital, Hangzhou, China

2 Department of Clinical Laboratory, Zhejiang Xiaoshan Hospital, Hangzhou, China

3 Cancer Center of Zhejiang Xiaoshan Hospital, Hangzhou, China

4 Department of Oncology, The First People’s Hospital of Xiaoshan, Hangzhou, China

5 Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, USA

Abstract

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.
Conclusion. 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.

Key words

colorectal cancer, polymorphism, oxaliplatin, survival, XPD

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