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

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

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8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)135-41
Number of pages7
JournalThe pharmacogenomics journal
Volume14
Issue number2
DOIs
Publication statusPublished - Apr 2014

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms
  • Disease-Free Survival
  • Female
  • Fluorouracil
  • Humans
  • Male
  • Middle Aged
  • NAV1.1 Voltage-Gated Sodium Channel
  • Neoplasm Staging
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Sex Characteristics

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