WORLD JOURNAL OF ADVANCE
HEALTHCARE RESEARCH

Dr. Kinjal K. Gajjar, Dr. Toral P. Kobawala, Dr. Hemangini H. Vora and Dr. Nandita R. Ghosh*

ABSTRACT

Background: GSTP1 plays a central role in the inactivation of toxic and carcinogenic electrophiles, including platinum compounds. In colorectal cancer (CRC) patients treated with oxaliplatin-based therapy, GSTP1 polymorphism and protein expression found to play significant correlation with prognosis but showed conflicting results. Present study assessed the association of GSTP1 Ile105Val polymorphism and protein expression with survival as well as clinicopathological parameters in CRC patients. Materials and Methods: GSTP1 polymorphism was examined by PCR-RFLP and protein expression was studied by immunohistochemistry in 143 untreated CRC patients. Results: GSTP1 Ile105Val polymorphism showed 51% A/A wild type, 42% A/G heterozygous and 7% G/G variant genotypes. Significant association of GSTP1 polymorphism was noted with family history (P=0.020) and tumor site (P=0.036). Variant G/G genotype was associated with unfavorable prognosis in total CRC, advanced stage and rectal cancer patients. The subgroup of patients having variant genotypes treated with combined 5-FU/oxaliplatin drug had a significant higher incidence of disease relapse and death as compared to those treated with single 5-FU drug. In relation to protein expression, GSTP1 cytoplasmic and/or nuclear immunoreactivity was noted in 95% CRC patients. Cytoplasmic GSTP1 expression was significantly associated with age (P=0.042) and histologic type (P=0.017). Low cytoplasmic as well as low nuclear GSTP1 expression correlated with worse survival in early stage, whereas showed better prognosis in advanced stage patients. Conclusion: GSTP1 Ile105Val polymorphism as well as its protein expression could be useful prognostic biomarkers in CRC patients.

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