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. 2018 Sep;36(3):218-226.
doi: 10.3857/roj.2018.00094. Epub 2018 Sep 30.

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

Luca Nicosia  1 , Giovanna Gentile  2 , Chiara Reverberi  1 , Giuseppe Minniti  3 , Maurizio Valeriani  1 , Vitaliana de Sanctis  1 , Luca Marinelli  1 , Fabiola Cipolla  2 , Ottavia de Luca  4 , Maurizio Simmaco  2 , Mattia F Osti  1
Affiliations

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

Luca Nicosia et al. Radiat Oncol J. 2018 Sep.

Abstract

Purpose: Standard 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 methods: Genotypes GSTP1 (A313G) and XRCC1 (G28152A) were determined by pyrosequencing technology in 80 patients affected by locally advanced rectal cancer.

Results: The 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).

Conclusion: Our 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.

Keywords: Genetic marker; Prognostic factor; Radiochemotherapy; Rectal cancer; Single nucleotide polymorphism; Tumor response.

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Conflict of interest statement

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1.
Fig. 1.
Single nucleotide polymorphisms characteristics and response to treatment according to allelic assessment (n = 80). GSTP1, glutathione S-transferase pi; XRCC1, X-ray repair cross-complementing 1; TRG, tumour regression grade.
Fig. 2.
Fig. 2.
Overall survival stratified for GSTP1 AA+AG vs. GG.
Fig. 3.
Fig. 3.
Cancer-specific survival stratified for GSTP1 AA+AG vs. GG.
See this image and copyright information in PMC

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