Gwas-Identified Telomere Length Associated Genetic Variants Predict Risk of Recurrence of HPV-Positive Oropharyngeal Cancer After Definitive Radiotherapy

Authors

Peng Sun
Peng Wei
Hongliang Liu
Jia Wu
Neil D Gross
Andrew G Sikora
Qingyi Wei
Sanjay Shete
Mark E Zafereo
Jisheng Liu
Guojun Li

Publication Date

8-1-2023

Journal

eBioMedicine

Abstract

BACKGROUND: Lymphocyte telomere length (LTL)-related genetic variants may modulate LTL and affect recurrence of squamous cell carcinoma of the oropharynx (SCCOP).

METHODS: A total of 1013 patients with incident SCCOP were recruited and genotyped for 16 genome-wide association study (GWAS)-identified TL-related polymorphisms. Of these patients, 489 had tumour HPV16 status determination. Univariate and multivariate analyses were performed to evaluate associations.

FINDINGS: Of the 16 TL-related polymorphisms, four were significantly associated with LTL: rs1920116, rs3027234, rs6772228, and rs11125529, and the patients with putatively favourable genotypes had approximately 1.5-3 times the likelihood of shorter LTL compared with patients with the corresponding risk genotypes. Moreover, patients with one to four favourable genotypes of the four combined polymorphisms had approximately 3-11 times the likelihood of shorter LTL compared with patients with no favourable genotype. The four LTL-related polymorphisms were significantly associated with approximately 40% reduced risk (for favourable genotypes) or doubled risk (for risk genotypes) of recurrence, and similar but more pronounced associations were observed in patients with tumour HPV16-positive SCCOP. Similarly, patients with one to four risk genotypes had significantly approximately 2.5-4 times increased recurrence risk compared with patients with no risk genotype, and similar but more pronounced associations were observed in patients with tumour HPV16-positive SCCOP.

INTERPRETATION: Four LTL-related polymorphisms individually or jointly modify LTL and risk of recurrence of SCCOP, particularly HPV-positive SCCOP. These LTL-related polymorphisms could have potential to further stratify patients with HPV-positive SCCOP for individualized treatment and better survival.

FUNDING: Not applicable.

Keywords

Humans, Genome-Wide Association Study, Papillomavirus Infections, Oropharyngeal Neoplasms, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Squamous Cell, Head and Neck Neoplasms, Telomere, Polymorphism, Single Nucleotide, Leukocytes

Comments

PMID: 37487414