Glutathione-S-transferase genes polymorphisms predict response and progression free survival in head and neck cancer patients treated with cisplatin based chemoradiotherapy

Abstract

21127 Background: Alterations in the function of DNA repair genes and detoxification genes may influence response to cisplatin based chemoradiotherapy in patients (pts) with head and neck cancer. Our purpose was to evaluate the prognostic ability of polymorphisms of three genes glutathione S-transferase (GST), ERCC1 and XPD in patients with head and neck squamous cell carcinoma (HNSCC). Methods: A polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) or multiplex PCR approach was used to determine the frequency of the XPD Lys751Gln (n=29), ERCC1 Asn118 (n=50), GSTP1 Ile105Val (n=22) and GSTT1/GSTM1 (n=66), in DNA of peripheral lymphocytes. A total of 50 pts were treated with platinum based chemoradiotherapy exclusively and 16 pts received the same regimen in the adjuvant setting. Median follow-up was 6.4 months and 17 pts had tumor progression and 2 died, with a progression free survival (PFS) of 18 months. Results: The frequencies (%) of the distinct genotypes were, respectively, for the homozygous common allele and heterozygous plus homozygous polymorphic variant: 40 and 60 for ERCC1; 48 and 52 for XPD; 36 and 64 for GSTT/GSTM1, 41 and 59 for GSTP1. We did not observe any association between ERCC1, XPD, GSTM1/GSTT1 polymorphisms and response, but for GSTP1, the polymorphic variant was associated with tumor response, as compared to wild type (p=0.069 χ2 test). In relation to PFS, no associations were found between XPD, ERCC1 and GSTP1, however, for GSTM1/GSTT1, the null or heterozygous genotype (median survival: not reached, n=43) was associated with a better PFS, as compared to the wild type (18 months, n=23; p=0.087, Log-rank). Conclusions: Among the polymorphic variants studied here, our impression is that GST is the most powerful prognostic factor of favorable response and PFS to cisplatin based chemoradiotherapy in HNSCC. Supported by CAPES. No significant financial relationships to disclose.