Abstract
OBJECTIVE: To evaluate the association between GSTP1 rs1695 A>G polymorphism and colorectal cancer (CRC) risk in an Iranian cohort, and to validate findings through a systematic review and meta-analysis. METHODS: A multicenter case-control study was conducted in Tehran hospitals, including CRC patients and matched controls. Demographic and clinical data were collected, and DNA was extracted from FFPE tissues and blood. Genotyping of GSTP1 rs1695 was performed using TaqMan® real-time PCR, with 5% of samples validated by direct sequencing. Logistic regression adjusted for age and gender was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), with Bonferroni correction applied. A systematic review and meta-analysis was performed following PRISMA guidelines using five databases, including studies up to January 2025. RESULTS: The study included 2,590 participants (1,038 CRC cases). CRC incidence was higher in individuals aged ≥50 years, with no significant gender difference. Colon cancer was more common, and most tumors were moderate or well differentiated at stages II-III. The GA genotype of GSTP1 rs1695 was significantly associated with increased CRC risk (p = 0.013), especially in those aged ≥50 years (p = 0.003). The combined AA + AG genotypes were also associated with increased risk (p = 0.016). Among females, the G allele showed higher CRC susceptibility, especially in older age (p = 0.0001). The meta-analysis of 30 studies (21,376 individuals) showed no overall association between rs1695 and CRC risk, but Iranian subgroup data indicated a modest association in AG vs. GG and AA+AG vs. GG models, which lost significance after Bonferroni correction. No publication bias was detected. CONCLUSION: The Iranian cohort showed an age- and gender-specific association between GSTP1 rs1695 and CRC risk. However, the meta-analysis did not support a consistent link, suggesting possible population-specific effects.