SH3D21 rs34416442 genetic variation is associated with pancreatic cancer patients' overall survival and their response to gemcitabine.

Pancreatic cancer remains one of the most lethal malignancies worldwide due to late diagnosis and limited therapeutic response. Gemcitabine is widely used as a first-line chemotherapeutic agent, and SH3D21 has been identified as a gemcitabine sensitizer in pancreatic cancer cells. Here, we investigated whether rs34416442 polymorphism of SH3D21 is associated with overall survival in a cohort of Iranian patients with pancreatic cancer. Peripheral blood samples were collected from 26 patients, and genotyping was performed. Patients were followed and survival outcomes were analyzed using Kaplan-Meier curves and the log-rank test. Three genotypes-TTT/TTT, TTT/T, and T/T-were identified with frequencies of 38%, 54%, and 8%, respectively. Significant differences in survival were observed among genotypes (p = 0.004). Patients carrying the T/T genotype exhibited markedly shorter mean overall survival (135 days) compared with those harboring at least one TTT allele (395 and 450 days). A recessive model further confirmed the reduced survival associated with the homozygous T/T genotype (p = 0.001). Stratified analyses showed that this association persisted in both gemcitabine-received (p = 0.006) and not-received (p = 0.016) subgroups. While different genotype-based survival patterns were observed among patients of the two groups. The TTT/T genotype showed the best survival in patients receiving gemcitabine, while TTT/TTT genotype did so in patients not receiving gemcitabine. These findings suggest SH3D21 rs34416442 as a potential predictive biomarker for pancreatic cancer.