Association of hTERT MNS16A polymorphism with clinical outcomes of North Indian lung cancer patients undergoing platinum-based doublet chemotherapy.

Background: Telomerase has been linked to aging and cancer. The MNS16A polymorphism in the hTERT gene plays a significant role in modulating telomerase activity and highlights the complexity of telomere-related genetics in cancer research.

Experimental Design: We genotyped 401 lung-cancer samples treated with platinum-based chemotherapy to identify the MNS16A polymorphism. We assessed overall survival using the Kaplan-Meier method and Cox regression analysis for adjusted hazard ratios. Stratified analyses evaluated risks for subgroups based on clinicopathologic parameters, outcomes, and toxicity calculated.

Results: Our findings show no significant link between MNS16A polymorphism and lung-cancer survival. However, in squamous cell carcinoma (SQCC) patients, the SS genotype was associated with poorer survival (p = 0.004). Patients with LS + SS genotypes responded better to gemcitabine in univariate (p = 0.003) and multivariate analyses (p = 0.014). The LS genotype was linked to a lower risk of progression to stage 4 (p = 0.011) and metastasis (p = 0.015) but an increased risk of T4 tumor size (p = 0.026). No significant correlations were found between MNS16A polymorphism and treatment-related toxicities.

Conclusion: The MNS16A polymorphism does not significantly impact overall lung-cancer survival but affects specific subgroups, influencing certain lung-cancer subtypes and treatment responses while having limited predictive value for overall outcomes or toxicity risks.