Genetic variations associated with telomere length predict the risk of recurrence of non-oropharyngeal head and neck squamous cell carcinoma

被引：0

作者：

Sun, Peng ^{[1
,2
]}

Gu, Kyle J. ^{[2
,3
]}

Zheng, Guibin ^{[2
,4
]}

Sikora, Andrew G. ^{[2
]}

Li, Chao ^{[2
,5
]}

Zafereo, Mark ^{[2
]}

Wei, Peng ^{[6
]}

Wu, Jia ^{[7
]}

Shete, Sanjay ^{[8
]}

Liu, Jisheng ^{[1
]}

Li, Guojun ^{[2
]}

机构：

[1] Soochow Univ, Dept Otolaryngol, Affiliated Hosp 1, 188 Shizi Rd, Suzhou 215006, Jiangsu, Peoples R China

[2] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Unit 1445,1515 Holcombe Blvd, Houston, TX 77030 USA

[3] Texas Tech Univ, Hlth Sci Ctr, Sch Med, Lubbock, TX USA

[4] Qingdao Univ, Yantai Yuhuangding Hosp, Dept Thyroid Surg, Yantai, Shandong, Peoples R China

[5] Univ Elect Sci & Technol China, Sichuan Canc Hosp & Inst, Sichuan Clin Res Ctr Canc, Sichuan Canc Ctr,Affiliated Canc Hosp,Dept Head &, Chengdu, Peoples R China

[6] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX USA

来源：

MOLECULAR CARCINOGENESIS | 2024年 / 63卷 / 09期

关键词：

biomarkers; genetic variant; non-OPHNSCC; recurrence; smoking-related head and neck cancer; telomere length; GENOME-WIDE ASSOCIATION; TNF-ALPHA PROMOTER; CIGARETTE-SMOKING; LUNG-CANCER; VARIANTS; TERT; BREAST; LOCI; POLYMORPHISMS; MUTATIONS;

D O I：

10.1002/mc.23768

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1722 / 1737

页数：16

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