TGF-β1 and TGF-βR1 play important roles in immune and inflammatory responses. Genetic variants of TGF-β1 rs1800470 and TGF-βR1 rs334348 have emerged as potentially prognostic biomarkers for HPV-related head and neck cancer, while their prognostic effect on survival of smoking-related head and neck cancer remains unknown. This study included 1403 patients with smoking-related head and neck cancer, and all these patients were genotyped for TGF-β1 rs1800470 and TGF-βR1 rs334348. Both univariate and multivariate analyses were performed to evaluate associations between the two functional genetic variants in microRNA binding sites of TGF-β1 and TGF-βR1 and survivals. Patients with TGF-β1 rs1800470 CT or CC genotype had 30–35% risk reductions for OS, DSS, and DFS compared to patients with TT genotype among overall patients, ever smokers, and patients administered chemoradiation. Furthermore, patients with TGF-βR1 rs334348 GA or GG genotype had significant 50–60% risk reductions for OS, DSS, and DFS compared to patients with AA genotype among overall patients and patients administered chemoradiation; among ever smokers, the risk reductions even reached 60–70%. The TCGA dataset was used for validation. These findings suggest that TGF-β1 rs1800470 and TGF-βR1 rs334348 significantly affect survival outcomes in patients with smoking-related head and neck cancer, especially in the subgroups of ever smokers and patients treated with chemoradiation. These genetic variants may serve as prognostic indicators for patients with smoking-related head and neck cancer and could play a role in advancing the field of personalized chemoradiation, thereby improving patient survival and quality of life.

TGF-β1 和 TGF-βR1 在免疫和炎症反应中发挥重要作用。TGF-β1 rs1800470 和TGF-βR1 rs334348的遗传变异已成为 HPV 相关头颈癌的潜在预后生物标志物，但它们对吸烟相关头颈癌生存的预后影响仍不清楚。该研究纳入了 1403 名与吸烟相关的头颈癌患者，所有这些患者均进行了TGF-β1 rs1800470 和TGF-βR1 rs334348 基因分型。进行单变量和多变量分析以评估TGF-β1和TGF-βR1的microRNA结合位点的两种功能性遗传变异与生存之间的关联。在总体患者、曾经吸烟者和接受放化疗的患者中，与 TT 基因型患者相比，TGF-β1 rs1800470 CT 或 CC 基因型患者的 OS、DSS 和 DFS 风险降低 30-35%。此外，在总体患者和接受放化疗的患者中，与 AA 基因型患者相比，TGF-βR1 rs334348 GA 或 GG 基因型患者的 OS、DSS 和 DFS 风险显着降低 50-60%；在曾经吸烟的人中，风险降低甚至达到 60-70%。 TCGA 数据集用于验证。这些发现表明，TGF-β1 rs1800470 和TGF-βR1 rs334348 显着影响吸烟相关头颈癌患者的生存结果，特别是在曾经吸烟者和接受放化疗的患者亚组中。这些基因变异可以作为与吸烟相关的头颈癌患者的预后指标，并可以在推进个性化放化疗领域发挥作用，从而提高患者的生存率和生活质量。