Single nucleotide polymorphism of GSTP1 and pathological complete response in locally advanced rectal cancer patients treated with neoadjuvant concomitant radiochemotherapy

Abstract

PurposeStandard treatment for locally advanced rectal cancer consists of neoadjuvant radiochemotherapy with concomitant fluoropyrimidine or oxaliplatin and surgery with curative intent. Pathological complete response has shown to be predictive for better outcome and survival; nevertheless there are no biological or genetic factors predictive for response to treatment. We explored the correlation between the single nucleotide polymorphisms (SNPs) GSTP1 (A313G) and XRCC1 (G28152A), and the pathological complete response and survival after neoadjuvant radiochemotherapy in locally advanced rectal cancer patients.Materials and MethodsGenotypes GSTP1 (A313G) and XRCC1 (G28152A) were determined by pyrosequencing technology in 80 patients affected by locally advanced rectal cancer.ResultsThe overall rate of pathological complete response in our study population was 18.75%. Patients homozygous AA for GSTP1 (A313G) presented a rate of pathological complete response of 26.6% as compared to 8.5% of the AG+GG population (p = 0.04). The heterozygous comparison (AA vs. AG) showed a significant difference in the rate of pathological complete response (26.6% vs. 6.8%; p = 0.034). GSTP1 AA+AG patients presented a 5- and 8-year cancer-specific survival longer than GSTP1 GG patients (87.7% and 83.3% vs. 44.4% and 44.4%, respectively) (p = 0.014). Overall survival showed only a trend toward significance in favor of the haplotypes GSTP1 AA+AG. No significant correlations were found for XRCC1 (G28152A).ConclusionOur results suggest that GSTP1 (A313G) may predict a higher rate of pathological complete response after neoadjuvant radiochemotherapy and a better outcome, and should be considered in a more extensive analysis with the aim of personalization of radiation treatment.

Outcomes of Radiotherapy for Mesenchymal and Non-Mesenchymal Subtypes of Gastric Cancer

“…Although the optimal indications of adjuvant XP-RT remain controversial, RT is still one of the most valuable and important treatment modalities in the management of GC, especially in the neoadjuvant or palliative setting. Furthermore, there is a rapid development of RT technology [23], also accompanied by an increased understanding of radiation biology [24,25]. In this respect, evaluating and comparing the effects of RT on GC of the mesenchymal subtype is of paramount importance, considering its heterogeneity and difficult therapeutic management.…”

Germline and Somatic Pharmacogenomics to Refine Rectal Cancer Patients Selection for Neo-Adjuvant Chemoradiotherapy

“…Glutathione-S-transferases (GSTs) is a multigene family of phase II metabolic enzymes employed in the detoxification of reactive oxygen intermediates produced by a wide variety of potentially toxic and carcinogenic compounds, by conjugation with glutathione (Nicosia et al, 2018). The missense polymorphism 313A > G (Ile105Val, rs1695) in GSTP1 was proposed, in a study from Nicosia et al, (2018) to be a predictive and prognostic marker. Among a population of 80 patients with LARC, those with a 313AA genotype for GSTP1 rs1695presented a rate of 26.6% of pCR compared to 8.5% of the 313AG/GG population.…”