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- Title
Association of SUMO1 and UBC9 genotypes with tumor response in non-small-cell lung cancer treated with irinotecan-based chemotherapy.
- Authors
Ji-Youn Han; Geon Kook Lee; Sun Young Yoo; Sung Jin Yoon; Eun Young Cho; Heung Tae Kim; Jin Soo Lee
- 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.
- Subjects
UBIQUITIN; DNA topoisomerase I; SMALL cell lung cancer; LUNG cancer; PHARMACOGENOMICS
- Publication
Pharmacogenomics Journal, 2010, Vol 10, Issue 2, p86
- ISSN
1470-269X
- Publication type
Article
- DOI
10.1038/tpj.2009.46