Full Text:   <3422>

CLC number: R734.2

On-line Access: 2012-11-05

Received: 2012-03-18

Revision Accepted: 2012-05-15

Crosschecked: 2012-10-08

Cited: 17

Clicked: 7800

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2012 Vol.13 No.11 P.875-883


XRCC1 Arg399Gln and clinical outcome of platinum-based treatment for advanced non-small cell lung cancer: a meta-analysis in 17 studies

Author(s):  Jian Chen, Qing-wei Zhao, Gen-ming Shi, Lin-run Wang

Affiliation(s):  Department of Pharmacy, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; more

Corresponding email(s):   Linrunw@yahoo.com.cn

Key Words:  Meta-analysis, XRCC1, Arg399Gln, Non-small cell lung cancer (NSCLC), Response, Survival

Jian Chen, Qing-wei Zhao, Gen-ming Shi, Lin-run Wang. XRCC1 Arg399Gln and clinical outcome of platinum-based treatment for advanced non-small cell lung cancer: a meta-analysis in 17 studies[J]. Journal of Zhejiang University Science B, 2012, 13(11): 875-883.

@article{title="XRCC1 Arg399Gln and clinical outcome of platinum-based treatment for advanced non-small cell lung cancer: a meta-analysis in 17 studies",
author="Jian Chen, Qing-wei Zhao, Gen-ming Shi, Lin-run Wang",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T XRCC1 Arg399Gln and clinical outcome of platinum-based treatment for advanced non-small cell lung cancer: a meta-analysis in 17 studies
%A Jian Chen
%A Qing-wei Zhao
%A Gen-ming Shi
%A Lin-run Wang
%J Journal of Zhejiang University SCIENCE B
%V 13
%N 11
%P 875-883
%@ 1673-1581
%D 2012
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1200083

T1 - XRCC1 Arg399Gln and clinical outcome of platinum-based treatment for advanced non-small cell lung cancer: a meta-analysis in 17 studies
A1 - Jian Chen
A1 - Qing-wei Zhao
A1 - Gen-ming Shi
A1 - Lin-run Wang
J0 - Journal of Zhejiang University Science B
VL - 13
IS - 11
SP - 875
EP - 883
%@ 1673-1581
Y1 - 2012
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1200083

Objective: XRCC1 polymorphism is a research hotpot in individual treatment for non-small cell lung cancer (NSCLC). To obtain the association between XRCC1 polymorphism and clinical outcome of platinum-based treatment for NSCLC, a meta-analysis was conducted. Methods: Databases including PubMed, Embase, Cochrane, and Chinese National Knowledge Infrastructure (CNKI) were searched for publications that met the inclusion criteria. A fixed effect model was used to estimate pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) for the association between XRCC1 arg399Gln and response or survival of platinum-based treatment for advanced NSCLC. A chi-squared-based Q-test was used to test the heterogeneity hypothesis. Egger’s test was used to check publication bias. Results: Seventeen published case-control studies that focus on the association between XRCC1 arg399Gln and response or survival of platinum-based treatment for advanced NSCLC in 2256 subjects were included in this meta-analysis, of whom 522 were AA genotypes (23.2% frequency), 916 AG genotypes (40.6% frequency), and 818 GG genotypes (36.2% frequency). The overall response rate (ORR) was 45.2% (110/243) for AA genotype patients, 29.9% for AG genotype (73/244), and 30.7% for GG genotype (124/403). The heterogeneity test did not show any heterogeneity and the Egger’s test did not reveal an obvious publication bias among the included studies. The meta-analysis indicated that AA genotype patients presented higher response rates toward platinum drug treatment compared with G model (GG+GA) patients (GG vs. AA model: OR=0.489, 95% CI 0.266–0.900, P=0.021; AG vs. AA model: OR=0.608, 95% CI 0.392–0.941, P=0.026; GA+AA vs. GG model: OR=1.259, 95% CI 0.931–1.701, P=0.135; GG+GA vs. AA model: OR=0.455, 95% CI 0.313–0.663, P=0.0001). However, no evidence validates XRCC1 associates with the survival following platinum drug therapy. Conclusions: Our meta-analysis suggested that XRCC1 arg399Gln is related with the sensitivity of NSCLC patients to platinum-based treatment. AA genotype patients present more desirable curative effectiveness compared with other patients.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Bidoli, P., Zilembo, N., Cortinovis, D., Mariani, L., Isa, L., Aitini, E., Cullura, D., Pari, F., Nova, P., Mancin, M., et al., 2007. Randomized phase II three-arm trial with three platinum-based doublets in metastatic non-small-cell lung cancer. An Italian Trials in Medical Oncology study. Ann. Oncol., 18(3):461-467.

[2]de las Penas, R., Sanchez-Ronco, M., Alberola, V., Taron, M., Camps, C., Garcia-Carbonero, R., Massuti, B., Queralt, C., Botia, M., Garcia-Gomez, R., et al., 2006. Polymorphisms in DNA repair genes modulate survival in cisplatin/gemcitabine-treated non-small-cell lung cancer patients. Ann. Oncol., 17(4):668-675.

[3]Ding, C.L., Liu, L.H., Song, H.F., 2010. Polymorphism in XRCC1 and sensitivity to platinum-based chemotherapy in advanced non-small cell lung cancer. China Pharmacist., 13(10):8-12 (in Chinese).

[4]Dong, J., Hu, Z., Shu, Y., Pan, S., Chen, W., Wang, Y., Hu, L., Jiang, Y., Dai, J., Ma, H., et al., 2012. Potentially functional polymorphisms in DNA repair genes and non-small-cell lung cancer survival: a pathway-based analysis. Mol. Carcinog., 51(7)546-552.

[5]Fan, H., Huang, X.E., Zhang, Q., Gao, L.L., Xu, L., Qi, G.F., Shen, H.B., 2008. Relationship of XRCC1 and XPD gene polymorphisms with chemosensitivity to platinum-based chemotherapy in advanced non-small cell lung cancer. Pract Geriatr., 22(4):306-314 (in Chinese).

[6]Gao, C.M., Shi, M.Q., Wu, J.Z., Cao, H.X., Feng, J.F., Xu, L., 2006. Polymorphisms in XRCC1 gene and sensitivity to gemcitabine/cisplatin chemtherapy in non-small cell lung cancer. Pract. J. Cancer, 21(4):351-353 (in Chinese).

[7]Giachino, D.F., Ghio, P., Regazzoni, S., Mandrile, G., Novello, S., Selvaggi, G., Gregori, D., DeMarchi, M., Scagliotti, G.V., 2007. Prospective assessment of XPD Lys751Gln and XRCC1 Arg399Gln single nucleotide polymorphisms in lung cancer. Clin. Cancer Res., 13(10):2876-2881.

[8]Gurubhagavatula, S., Liu, G., Park, S., Zhou, W., Su, L., Wain, J.C., Lynch, T.J., Neuberg, D.S., Christiani, D.C., 2004. XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy. J. Clin. Oncol., 22(13):2594-2601.

[9]Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., Thun, M., 2009. Cancer statistics, 2009. CA Cancer J. Clin., 59(4):225-249.

[10]Joerger, M., Burgers, S.A., Baas, P., Smit, E.F., Haitjema, T.J., Bard, M.P., Doodeman, V.D., Smits, P.H.M., Vincent, A., Huitema, A.D.R., et al., 2012. Germline polymorphisms in patients with advanced nonsmall cell lung cancer receiving first-line platinum-gemcitabine chemotherapy: a prospective clinical study. Cancer, 118(9):2466-2475.

[11]Kalikaki, A., Kanaki, M., Vassalou, H., Souglakos, J., Voutsina, A., Georgoulias, V., Mavroudis, D., 2009. DNA repair gene polymorphisms predict favorable clinical outcome in advanced non-small-cell lung cancer. Clin. Lung Cancer, 10(2):118-123.

[12]Kang, C.H., Jang, B.G., Kim, D.W., Chung, D.H., Kim, Y.T., Jheon, S., Sung, S.W., Kim, J.H., 2010. The prognostic significance of ERCC1, BRCA1, XRCC1, and βIII-tubulin expression in patients with non-small cell lung cancer treated by platinum- and taxane-based neoadjuvant chemotherapy and surgical resection. Lung Cancer, 68(3):478-483.

[13]Lamerdin, J.E., Montgomery, M.A., Stilwagen, S.A., Scheidecker, L.K., Tebbs, R.S., Brookman, K.W., Thompson, L.H., Carrano, A.V., 1995. Genomic sequence comparison of the human and mouse XRCC1 DNA repair gene regions. Genomics, 25(2):547-554.

[14]Li, D., Zhou, Q., Liu, Y., Yang, Y., Li, Q., 2012. DNA repair gene polymorphism associated with sensitivity of lung cancer to therapy. Med. Oncol., 29(3):1622-1628.

[15]Liu, X.Z., Qian, X.P., Liu, B.R., Hu, W.J., Wang, L.F., Wei, J., Yu, L.X., 2008. Single nucleotide polymorphisms in XRCC1, XPD and platinum prognosis in non-small-cell lung cancer patients. J. Clin. Med. Pract., 12(5):7-11 (in Chinese).

[16]Lunn, R.M., Langlois, R.G., Hsieh, L.L., Thompson, C.L., Bell, D.A., 1999. XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. Cancer Res., 59(11):2557-2561.

[17]Mohrenweiser, H.W., Xi, T., Vazquez-Matias, J., Jones, I.M., 2002. Identification of 127 amino acid substitution variants in screening 37 DNA repair genes in humans. Cancer Epidemiol. Biomarkers Prev., 11(10 Pt 1):1054-1064.

[18]National Comprehensive Cancer Network, 2011. NCCN Clinical Practive Guidelines in Oncology (NCCN Guidelines): Non-small Cell Lung Cancer. Version 2. Available from http://www.nccn.com [Accessed on May 3, 2011].

[19]Parmar, M.K., Torri, V., Stewart, L., 1998. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat. Med., 17(24):2815-2834.

[20]Pfister, D.G., Johnson, D.H., Azzoli, C.G., Sause, W., Smith, T.J., Baker, S.Jr., Olak, J., Stover, D., Strawn, J.R., Turrisi, A.T., et al., 2004. American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003. J. Clin. Oncol., 22(2):330-353.

[21]Qian, X.P., Qiu, L.X., Yang, Y., Jiang, M., Zhang, Y., Yu, L.X., Wang, L.F., Hu, W.J., Liu, B.D., 2010. Predictive value of base-excision repair gene polymorphisms in advanced non-small cell lung cancer patients receiving platinum-based chemotherapy. J. Modern Oncol., 18(7):132-138 (in Chinese).

[22]Shellard, S., Fichtinger-Schepman, A., Lazo, J., 1993. Evidence of differential cisplatin-DNA adduct formation, removal and tolerance of DNA damage in three human lung carcinoma cell lines. Anti-cancer Drugs, 4(4):491-500.

[23]Shen, M.R., Jones, I.M., Mohrenweiser, H., 1998. Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res., 58(4):604-608.

[24]Spruance, S.L., Reid, J.E., Grace, M., Samore, M., 2004. Hazard ratio in clinical trials. Antimicrob. Agents Chemother., 48(8):2787-2792.

[25]Sun, X., Li, F., Sun, N., Shukui, Q., Baoan, C., Jifeng, F., Cheng, L., Lu, Z., Cheng, H., Cao, Y.D., et al., 2009. Polymorphisms in XRCC1 and XPG and response to platinum-based chemotherapy in advanced non-small cell lung cancer patients. Lung Cancer, 65(2):230-236.

[26]Thompson, L.H., Brookman, K.W., Jones, N.J., Allen, S.A., Carrano, A.V., 1990. Molecular cloning of the human XRCC1 gene, which corrects defective DNA strand break repair and sister chromatid exchange. Mol. Cell Biol., 10(12):6160-6171.

[27]Vilmar, A., Sørensen, J.B., 2009. Excision repair cross-complementation group 1 (ERCC1) in platinum-based treatment of non-small cell lung cancer with special emphasis on carboplatin: a review of current literature. Lung Cancer, 64(2):131-139.

[28]Wang, L.R., Zhang, G.B., Chen, J., Li, J., Li, M.W., Xu, N., Wang, Y., Shen, T.J.Z., 2011. RRM1 gene expression in peripheral blood is predictive of shorter survival in Chinese patients with advanced non-small-cell lung cancer treated by gemcitabine and platinum. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 12(3):174-179.

[29]Wang, Z.H., Miao, X.P., Tan, W., Zhang, X.R., Xu, B.H., Lin, D.X., 2004. Single nucleotide polymorphisms in XRCC1 and clinical response to platin-based chemotherapy in advanced non-small cell lung cancer. Chin. J. Cancer, 23(8):865-868 (in Chinese).

[30]Wells, G., Shea, B., O'Connell, D., Peterson, J., Welch, V., Losos, M., 2003. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses. Available from http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm [Accessed on Apr. 5, 2009].

[31]Yao, C.Y., Huang, X.E., Li, C., Shen, H.B., Shi, M.Q., Feng, J.F., Pan, L.X., Tang, J.H., 2009. Lack of influence of XRCC1 and XPD gene polymorphisms on outcome of platinum-based chemotherapy for advanced non small cell lung cancers. Asian Pac. J. Cancer Prev., 10(5):859-864.

[32]Yao, C.Y., Huang, X.E., Li, C., Li, Y., Xu, H.X., Shen, H.B., 2010. Relationship between the combination of XRCC1 and XPD gene polymorphisms with platinum-based chemotherapy in advanced non-small cell lung cancer. Acta Acad. Med. Xuzhou, 30(6):34-37 (in Chinese).

[33]Yuan, P., Miao, X.P., Zhang, X.M., Wang, Z.H., Tan, W., Sun, Y., Zhang, X.R., Lin, D.X., 2006. XRCC1 and XPD genetic polymorphisms predict clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer. Chin. J. Oncol., 28(3):196-199.

[34]Zhou, F., Yu, Z., Jiang, T., Lv, H., Yao, R., Liang, J., 2011. Genetic polymorphisms of GSTP1 and XRCC1: prediction of clinical outcome of platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Swiss Med. Wkly., 141:w13275.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE