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Gender-specific profiling in SCN1A polymorphisms and time-to-recurrence in patients with stage II/III colorectal cancer treated with adjuvant 5-fluoruracil chemotherapy

The Pharmacogenomics Journal volume 14, pages 135–141 (2014)Cite this article

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Abstract

This study was designed to analyze the gender-related association between SCN1A polymorphisms (voltage-gated sodium channels; α-subunit) and time-to-recurrence (TTR) in patients with colorectal cancer (CRC) treated with 5-fluoruracil (5-FU)-based adjuvant chemotherapy. We enrolled from a prospective database patients with stage II and III CRC treated with adjuvant 5-FU-based chemotherapy. Genotypes for SCN1A rs3812718 and rs229877 were determined by direct DNA sequencing. One hundred twenty-seven males and 107 females were included in the study. In the univariate and multivariate analysis, the shortest TTR was associated with female patients carrying the rs3812718-TT genotype (hazard ratio (HR): 2.26 (95% confidence interval (CI): 0.89, 5.70), P=0.039) but with male patients carrying the rs3812718-CC genotype (HR: 0.49 (95% CI: 0.18, 1.38), P=0.048). For rs229877 the CT genotype was associated with a trend for shorter TTR in both gender populations. The study validated gender-dependent association between genomic SCN1A rs3812718 polymorphism and TTR in CRC patients treated with adjuvant 5-FU-based chemotherapy. This study confirms that voltage-gated Na+ channels may be a potential therapeutic target and a useful predictive biomarker before 5-FU infusion.

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Authors and Affiliations

  1. Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    L Benhaim, A Gerger, P Bohanes, D Paez, T Wakatsuki, D Yang, M J LaBonte, Y Ning, R El-Khoueiry, F Loupakis, W Zhang & H J Lenz

  2. INSERM_UMR-S 775, Bases moléculaires de la réponse aux xénobiotiques, Université Paris Descartes, Paris, France

    L Benhaim & P Laurent-Puig

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  1. L Benhaim
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Correspondence to L Benhaim.

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Benhaim, L., Gerger, A., Bohanes, P. et al. Gender-specific profiling in SCN1A polymorphisms and time-to-recurrence in patients with stage II/III colorectal cancer treated with adjuvant 5-fluoruracil chemotherapy. Pharmacogenomics J 14, 135–141 (2014). https://doi.org/10.1038/tpj.2013.21

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