Breast cancer remains a leading cause of cancer-related morbidity in India, with its pathogenesis driven by complex molecular alterations in key signalling networks. Among these, aberrant activation of the Wnt/β-catenin pathway is a well-established contributor to tumorigenesis and disease progression. Glycogen synthase kinase-3 beta (GSK3β), a constitutively active serine/threonine kinase, serves as the catalytic core of the β-catenin destruction complex, and its activity is critical for maintaining Wnt pathway suppression. The rs334558 (G>C) promoter polymorphism of the GSK3B gene is predicted to alter transcription factor binding affinity, potentially reducing basal GSK3β expression and thereby influencing oncogenic susceptibility. Despite this mechanistic relevance, population-specific data from South Indian cohorts are absent from the literature.
Material and Method: A case-control design enrolled 50 histologically confirmed primary breast cancer patients from Nizam’s Institute of Medical Sciences (NIMS), Hyderabad, and 50 age- and sex-matched controls. Genomic DNA was extracted by the salting-out method. GSK3β rs334558 genotyping was performed by PCR-RFLP using the restriction endonuclease TaqI. Statistical analysis included allele frequency estimation, Pearson chi-square test, Yates’ continuity-corrected chi-square, and odds ratio (OR) calculation with 95% confidence intervals (CI) across all genotypic and clinical stratifications.
Result: The GSK3β rs334558 promoter polymorphism does not exhibit statistically significant independent association with breast cancer susceptibility in this South Indian cohort. However, the moderate elevation of the GC genotype and C allele in cases, and the genotype-specific trends across ER-negative and HER2-positive subgroups, suggest a candidate role for this variant in tumour subtype biology, warranting validation in larger, ethnically stratified multi-centre cohorts.