Department of Otolaryngology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Mol Carcinog. 2024 Sep;63(9):1722-1737. doi: 10.1002/mc.23768. Epub 2024 Jun 5.
Genetic factors underlying lymphocyte telomere length (LTL) may provide insights into genomic stability and integrity, with direct links to susceptibility to cancer recurrence. Polymorphisms in telomere-associated genes are strongly associated with LTL and cancer risk, while few large studies have explored the associations between LTL-related polymorphisms and recurrence risk of non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC). Totally 1403 non-OPHNSCC patients were recruited and genotyped for 16 LTL-related polymorphisms identified by genome-wide association studies. Univariate and multivariate analyzes were performed to evaluate associations between the polymorphisms and non-OPHNSCC recurrence risk. Patients carrying rs755017 GA/GG, rs2487999 TC/TT, rs2736108 TC/TT, or rs6772228 AT/AA genotypes exhibited shorter DFS than those with the rs755017 AA, rs2487999 CC, rs2736108 CC, or s6772228 TT genotypes, respectively (all log-rank p < 0.05). Multivariable analysis confirmed an increased risk of recurrence for patients carrying rs755017 GA/GG, rs2487999 TC/TT, rs2736108 TC/TT, or rs6772228 AT/AA genotypes (adjusted hazard ratio [aHR]: 1.66, 95% confidence interval [CI]: 1.32-2.07; aHR: 1.77, 95% CI: 1.41-2.23; aHR: 1.56, 95% CI: 1.22-1.99; aHR: 1.52, 95% CI: 1.20-1.93, respectively). Further stratified analysis revealed stronger associations between these genotypes and recurrence risk in ever-smokers and patients undergoing chemoradiotherapy. The similar but particularly pronounced results were observed for the combined risk genotypes of the four significant polymorphisms. This is the first large study on non-OPHNSCC patients showing that LTL-related polymorphisms may modify risk of non-OPHNSCC recurrence individually and jointly, particularly when analyzed in the context of smoking status and personized treatment. Larger studies are needed to validate these results.
遗传因素是淋巴细胞端粒长度（LTL）的基础，可能为基因组稳定性和完整性提供深入的见解，与癌症复发的易感性直接相关。端粒相关基因的多态性与 LTL 和癌症风险密切相关，而很少有大型研究探讨 LTL 相关多态性与非口咽头颈部鳞状细胞癌（非 OPHNSCC）复发风险之间的关系。总共招募了 1403 名非 OPHNSCC 患者，并对通过全基因组关联研究确定的 16 个 LTL 相关多态性进行了基因分型。进行单变量和多变量分析以评估多态性与非 OPHNSCC 复发风险之间的关联。与 rs755017 AA、rs2487999 CC、rs2736108 CC 或 rs6772228 TT 基因型相比，携带 rs755017 GA/GG、rs2487999 TC/TT、rs2736108 TC/TT 或 rs6772228 AT/AA 基因型的患者的无复发生存率更短（所有对数秩 p < 0.05）。多变量分析证实，携带 rs755017 GA/GG、rs2487999 TC/TT、rs2736108 TC/TT 或 rs6772228 AT/AA 基因型的患者复发风险增加（调整后的危险比[aHR]：1.66，95%置信区间[CI]：1.32-2.07；aHR：1.77，95%CI：1.41-2.23；aHR：1.56，95%CI：1.22-1.99；aHR：1.52，95%CI：1.20-1.93，分别）。进一步分层分析显示，这些基因型与吸烟和接受放化疗的患者的复发风险之间存在更强的关联。在四个显著多态性的联合风险基因型中观察到类似但更为显著的结果。这是第一项针对非 OPHNSCC 患者的大型研究，表明 LTL 相关多态性可能单独和共同改变非 OPHNSCC 复发的风险，特别是在吸烟状况和个体化治疗的背景下进行分析时。需要更大规模的研究来验证这些结果。
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