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Association of SUMO1 and UBC9 genotypes with tumor response in non-small-cell lung cancer treated with irinotecan-based chemotherapy

The Pharmacogenomics Journal volume 10, pages 86–93 (2010)Cite this article

Abstract

Irinotecan induces small ubiquitin-like modifier (SUMO)-1 conjugation to topoisomerase-I, leading to enhanced sensitivity to irinotecan. In this study, we genotyped SUMO1 and UBC9 polymorphisms in 147 non-small-cell lung cancer (NSCLC) treated with irinotecan chemotherapy to investigate the association between genotypes and tumor response rate. Immunohistochemistry for SUMO1 and UBC9 was performed in 42 tumor samples and correlated with genotypes. The UBC9 10920CG genotype was associated with significantly higher response rate than the C/C genotype (81 vs 37%, P=0.0002). This predictive effect on tumor response was also seen in multivariate analysis (odds ratio=8.5, P=0.003). Moreover, tumors arising from the UBC9 10920CG genotype were associated with higher prevalence of SUMO1 overexpression compared with those with CC genotype (78 vs 31%, P=0.021). This finding suggests that the UBC9 10920CG genotype enhances sensitivity to irinotecan chemotherapy in advanced NSCLC through upregulation of SUMO1 in tumor cells.

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Acknowledgements

This study was supported by a grant from National Cancer Center 0810130-2.

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Authors and Affiliations

  1. National Cancer Center, Research Institute and Hospital, Goyang-si, Gyeonggi-do, Republic of Korea

    Ji-Youn Han, Geon Kook Lee, Sun Young Yoo, Sung Jin Yoon, Heung Tae Kim & Jin Soo Lee

  2. DNALink Inc., Seoul, Korea

    Eun Young Cho

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Correspondence to Ji-Youn Han.

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Han, JY., Lee, G., Yoo, S. et al. Association of SUMO1 and UBC9 genotypes with tumor response in non-small-cell lung cancer treated with irinotecan-based chemotherapy. Pharmacogenomics J 10, 86–93 (2010). https://doi.org/10.1038/tpj.2009.46

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