The principal aim of the current study was to investigate the relationship between miR-149 T>C (rs2292832) and miR-196a2 C>T (rs11614913) small non-coding RNA polymorphisms and the risk of developing CRC in the Azerbaijani population. The study included 120 patients diagnosed with CRC and 125 healthy individuals. Peripheral blood samples were collected from all the subjects in EDTA tubes and DNA extraction was performed by salting out. Polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. While comparing without gender distinction no statistical correlation was found between the heterozygous TC (OR = 0.66; 95% CI = 0.37–1.15; p = 0.142), mutant CC (OR = 1.23; 95% CI = 0.62–2.45; p = 0.550), and mutant C (OR = 1.03; 95% CI = 0.72–1.49; p = 0.859) alleles of the miR-149 gene and the CT (OR = 1.23; 95% CI = 0.69–2.20; p = 0.485), mutant TT (OR = 1.29; 95% CI = 0.67–2.47; p = 0.452), and mutant T (OR = 1.17; 95% CI = 0.82–1.67; p = 0.388) alleles of the miR-196a2 gene and the risk of CRC. However, among women, miR-149 TC (OR = 0.43; 95% CI = 0.19–1.01; p = 0.048) correlated with a reduced risk of CRC, whereas miR-196a2 CT (OR = 2.77; 95% CI = 1.13–6.79; p = 0.025) correlated with an increased risk of CRC. Our findings indicated that miR-149 T>C (rs2292832) might play a protective role in the development of CRC in female patients, whereas the miR-196a2 (rs11614913) polymorphism is associated with an increased risk of CRC in women in the Azerbaijani population, highlighting the importance of gender dimorphism in cancer etiology.

Background: This study is the first to investigate the association between colorectal cancer (CRC) risk and the hMLH1 −93G>A and hMSH2 1032G>A polymorphisms of mismatch repair (MMR) genes in the Azerbaijani population. Methods: Peripheral blood samples containing EDTA were collected from the study subjects (134 patients and 137 controls), and genomic DNA was extracted using the non-enzymatic salting-out method. Genotypes were determined by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP), and the results were visualized through agarose gel electrophoresis. Results: Overall, no statistically significant correlation was observed between CRC risk and the hMLH1 −93G>A polymorphism in the heterozygous GA (OR = 0.760; 95% CI = 0.374–1.542; p = 0.446), the mutant AA (OR = 1.474; 95% CI = 0.738–2.945; p = 0.270), or the A allele (OR = 1.400; 95% CI = 0.984–1.995; p = 0.062). However, in contrast to the dominant model, a statistically significant association was found between the recessive model and an increased CRC risk, with an odds ratio of 1.788 (95% CI = 1.102–2.900; p = 0.018). The hMLH1 −93G>A polymorphism was identified at a significantly higher frequency across the TNM stages, with the distribution showing statistical significance (p < 0.05). Additionally, no statistically significant association was observed between the hMSH2 1032G>A polymorphism and CRC risk. Conclusions: Although no overall association was observed for hMLH1 −93G>A, our findings suggest a potential link with increased colorectal cancer risk under the recessive model in the Azerbaijani population. Further studies are warranted to confirm this model-specific association and investigate the underlying biological mechanisms.

Cancer is largely a disease of older adults, yet the framework used to explain how tumors evade immunity was built almost entirely on young, specific-pathogen-free mouse models and on clinical trials that under-enroll older adults. This review examines whether that framework holds when the host is old. Rather than surveying cancer immunology and aging comprehensively, it focuses on one question: whether the four host capacities the standard account of immunoediting and checkpoint blockade assumes still hold in the aged host. These are a naive T-cell repertoire wide enough to generate tumor-specific clones, a stromal environment that does not suppress priming, functional natural killer [NK] cell surveillance, and an immune baseline free of chronic inflammation. Aging alters all four, but not uniformly. Thymic involution and NK cell decline result in the immune system operating at reduced capacity, representing a shift in severity rather than a fundamental change in mechanism. The NK cell axis is disproportionately significant, as no approved therapies currently restore its function. In contrast, aged stromal senescence and inflammaging represent qualitative changes: the tissue environment becomes suppressive prior to tumor development, rather than as a consequence of tumor presence. The clinical evidence neither confirms nor refutes this interpretation. Older and younger patients gain similar benefit from checkpoint blockade, which is easily read as age being immunologically irrelevant. We argue instead that chronological age bundles aging changes acting on response in opposite directions. What predicts response is more accurately captured by immunological age than by chronological age. This reframing has a clear translational consequence. Therapeutic approaches should not only target the release of suppressed immune responses but also address the correction of the aged microenvironment. This hypothesis is currently being evaluated by senolytic strategies, which have been tested in an initial clinical trial and are supported by converging preclinical evidence.

Background: This study is the first to investigate the association between colorectal cancer (CRC) risk and the hMLH1 -93G>A and hMSH2 1032G>A polymorphisms of mismatch repair (MMR) genes in the Azerbaijani population. Methods: Peripheral blood samples containing EDTA were collected from the study subjects (134 patients and 137 controls), and genomic DNA was extracted using the non-enzymatic salting-out method. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the results were visualized through agarose gel electrophoresis. Results: Overall, no statistically significant correlation was observed between CRC risk and the hMLH1 -93G>A polymorphism in the heterozygous GA (OR=0.76; 95% CI=0.37–1.54; P=0.446), mutant AA (OR=1.47; 95% CI=0.74–2.95; P=0.270), or the A allele (OR=1.062; 95% CI=0.735–1.534; P=0.748). However, in contrast to the dominant model, a statistically significant association was found between the recessive model and a reduced CRC risk, with an odds ratio of 0.56 (95% CI=0.35–0.91; P=0.018). The hMLH1 -93G>A polymorphism was identified at a significantly higher frequency across the TNM stages, with the distribution showing statistical significance (P0.05). Additionally, no statistically significant association was observed between the hMSH2 1032G>A polymorphism and CRC risk. Conclusions: Our results indicate that the hMLH1 -93G>A polymorphism, particularly under the recessive model, may play a protective role against CRC risk in the Azerbajani population. Further studies are required to validate these results and investigate the underlying biological mechanisms.

Background: Breast cancer (BC) is the most common malignancy among women, and genetic predisposition plays a critical role in its development. Among DNA mismatch repair (MMR) genes, MLH1 is essential for maintaining genomic stability, and promoter variants may influence its transcriptional regulation. Variants in MMR genes, including MLH1, have been implicated in cancer susceptibility; however, evidence regarding the promoter polymorphism −93G>A (rs1800734) and its association with BC remains limited and inconsistent across populations. Methods: We conducted a case–control study of 143 breast cancer patients and 161 cancer-free controls of Azerbaijani origin. Genotyping of MLH1 −93G>A was performed using PCR-RFLP and validated by next-generation sequencing (NGS). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under different genetic models by logistic regression, followed by false discovery rate (FDR) correction for multiple testing. Results: The genotype distribution among patients was 25.9% GG, 58.7% GA, and 15.4% AA, compared with 37.9%, 46.6%, and 15.5% in controls. A significant association was observed between the GA genotype and BC risk (OR = 1.855, 95% CI: 1.104–3.085, p = 0.019). In the dominant model (GA + AA vs. GG), carriers of the A allele showed increased breast cancer risk (OR = 1.747, 95% CI: 1.069–2.856, p = 0.026). Genotype distribution was also associated with tumor grade (p = 0.047) and stage (p = 0.013). However, none of the associations remained significant after FDR adjustment. Conclusions: This pilot study provides the first evidence from Azerbaijan suggesting a potential role of the MLH1 −93G>A variant in breast cancer susceptibility. Although the associations were nominal and require validation in larger cohorts, the findings point to a biologically plausible link between MLH1 promoter variation and impaired MMR activity, which may contribute to polygenic breast cancer risk. These preliminary results emphasize the importance of evaluating MMR gene variants in underrepresented populations and support further studies integrating functional assays and broader gene coverage.