Md. Abdur Rahman

Background: Exonuclease 1 ( EXO1 ) is a key nuclease in the DNA mismatch repair (MMR) pathway and is involved in correcting replication errors while maintaining genomic stability. The K589E (rs1047840) single nucleotide polymorphism (SNP) of EXO1 has been associated with cancer susceptibility in different populations. Objectives: This study aimed to investigate the association between the EXO1 K589E polymorphism and breast cancer risk, as well as its relationship with selected clinicopathological characteristics in Bangladeshi women. Design: Hospital-based case-control study. Methods: The present case–control study included 184 patients with histologically confirmed breast cancer and 200 age-matched cancer-free controls. Genotyping of the EXO1 K589E variant was carried out using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) analysis and subsequently confirmed by direct sequencing. The associations between the polymorphism and breast cancer risk were assessed using logistic regression, with odds ratios (ORs) and corresponding 95% confidence intervals (CIs) calculated. Results: The frequencies of G/G, G/A, and A/A genotypes were 49.5, 41.8, and 8.7% among cases, compared with 69, 27.5, and 3.5% among controls, respectively. Both the heterozygous (G/A) and homozygous variant (A/A) genotypes were significantly associated with elevated breast cancer risk (OR= 2.12, 95% CI= 1.37-3.28, p = 0.0007; OR= 3.46, 95 % CI= 1.37-8.76, p = 0.0086, respectively). The combined variant genotypes (G/A + A/A) conferred a 2.27-fold higher risk ( p = 0.0001), and the A allele was also strongly associated with breast cancer predisposition (OR= 2.01, 95% CI= 1.43-2.84, p = 0.0001). The association remained significant under codominant, dominant, recessive, overdominant, and log-additive genetic models. Significant correlations were observed between the variant genotype and menopausal status, body mass index (BMI), and tumor stage. Conclusion: The results indicate that the EXO1 K589E polymorphism is significantly associated with an increased risk of breast cancer in Bangladeshi women and may also be related to key clinicopathological features of the disease.

Cadherin 1 ( CDH1 ) encodes E‐cadherin, a key epithelial adhesion molecule traditionally associated with tumor suppression and epithelial–mesenchymal transition (EMT). However, its roles across cancers remain incompletely understood, particularly within multilayer regulatory contexts involving genomic, epigenetic, transcriptional, and immune mechanisms. CDH1 expression, survival associations, EMT‐correlated gene profiles ( VIM , SNAI1 , and ZEB1 ), immune infiltration patterns, immune checkpoint correlations ( PDCD1 , CD274 , and CTLA4 ), promoter methylation, and genomic alterations were assessed across five epithelial cancers, breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), lung adenocarcinoma (LUAD), ovarian serous cystadenocarcinoma (OV), and stomach adenocarcinoma (STAD). Cross‐platform analysis was performed using The Cancer Genome Atlas (TCGA)/Genomic Data Commons (GDC) datasets, Gene Expression Profiling Interactive Analysis 2 (GEPIA2), UALCAN, TIMER, KM Plotter, cBioPortal, and g:Profiler. CDH1 was overexpressed but showed variable prognostic significance; TCGA/GDC analyses were nonsignificant, whereas KM Plotter showed better survival in COAD, LUAD, and STAD, worse survival in BRCA, and no association in OV. Classic inverse relationships between CDH1 and VIM or ZEB1 were evident only in STAD, and SNAI1 showed no consistent association. Immune infiltration patterns were tumor‐specific, ranging from cytotoxic T‐cell dominance in LUAD to macrophage‐rich profiles in OV; immune checkpoint correlations were similarly context‐dependent. Cancer‐specific enrichment revealed distinct trafficking‐ and adhesion‐related profiles. Promoter methylation patterns varied by cancer, whereas genomic alterations of CDH1 were rare. CDH1 does not function as a universal epithelial or EMT marker across epithelial cancers. Instead, its associations with EMT, immune contexture, methylation, and prognosis are context‐dependent, supporting a model of CDH1 as a heterogeneous regulator of epithelial plasticity. These findings challenge single‐function interpretations and support cancer‐specific CDH1 evaluation in translational research.

Background: CDH1 (E-cadherin) is a key epithelial adhesion molecule traditionally associated with tumor suppression and epithelial-mesenchymal transition (EMT). However, its roles across cancers remain incompletely understood, particularly within multilayer regulatory contexts involving genomic, epigenetic, transcriptional, and immune mechanisms. Methods: CDH1 expression, survival associations, EMT-correlated gene profiles (VIM, SNAI1, ZEB1), immune infiltration patterns, immune checkpoint correlations (PDCD1, CD274, CTLA4), promoter methylation, and genomic alterations were assessed across five epithelial cancers, breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), lung adenocarcinoma (LUAD), ovarian cancer (OV), and stomach adenocarcinoma (STAD). Cross-platform validation was performed using TCGA/GDC datasets, GEPIA2, UALCAN, TIMER, KM Plotter, cBioPortal, and g:Profiler. Results: CDH1 was overexpressed but showed variable prognostic significance; higher expression predicted better survival in COAD, LUAD and STAD, worse survival in BRCA and had no impact in OV. Classic inverse relationships between CDH1 and VIM or ZEB1 were evident only in STAD, and SNAI1 showed no consistent association. Immune infiltration patterns were tumor specific, ranging from cytotoxic T cell dominance in LUAD to macrophage rich profiles in OV; immune checkpoint correlations were similarly context dependent. Co expressed genes were enriched for endomembrane transport rather than adhesion pathways. Promoter methylation patterns varied by cancer, whereas genomic alterations of CDH1 were rare. Conclusions: CDH1 does not function as a universal epithelial or EMT marker across epithelial cancers. Instead, its associations with EMT, immune contexture, methylation, and prognosis are context-dependent, supporting a model of CDH1 as a heterogeneous regulator of epithelial plasticity. These findings challenge single-function interpretations and support cancer-specific CDH1 evaluation in translational research.