The Impact of GGH -401C>T Polymorphism on Cisplatin-based Chemoradiotherapy Response and Survival in Cervical Cancer

Aims: Cervical cancer is the third most frequent cancer in women worldwide, mostly treated with cisplatin-based chemoradiotherapy. Since it is known that folate metabolism might interfere with cisplatin effectiveness, we intended to study the influence of the Gamma Glutamyl Hydrolase -401C>T polymorphism in treatment response in cervical cancer.

Methods: We retrospectively reviewed the clinical data of 167 patients with bulky cervical cancer submitted to cisplatin-based chemoradiotherapy. The genotypes of GGH -401C>T SNP were determined by real-time PCR and statistical analysis was performed by χ(2) test and survival analysis.

Results: The genotypes of GGH-401C>T were significantly associated with the response to platinum-based chemoradiotherapy. Treatment response was higher in patients carrying the CC genotype, who presented a significant increased chance of treatment response (survival time in months/genotype: 91 for CC Vs 72 for CT/TT; p=0.035, log rank test). A Cox regression analysis accordingly showed that the presence of the T allele was significantly linked to a worse treatment response (HR=3.036; CI 95% 1.032-8.934, p=0.044).

Conclusions: The results of our study suggested the potential interest of GGH -401C>T as a predictive factor of the outcome of cervical carcinoma treated with cisplatin-based chemoradiotherapy.