Identification of single nucleotide pleomorphisms associated with periodontal disease in head and neck cancer irradiation patients by exome sequencing

Head and Neck Cancer

Talevi V, et al. Oral Surg Oral Med Oral Pathol Oral Radiol 2020.


OBJECTIVE: Periodontal disease (PD) is a common oral complication in patients with head and neck cancer (HNC) undergoing radiation therapy (RT). Our objective was to identify candidate single nucleotide polymorphisms (SNPs) associated with PD in radiation-treated patients with HNC.

STUDY DESIGN: DNA was extracted from the saliva of patients with HNC (n = 69) before RT. Clinical attachment loss (CAL) increment greater than 0.2 mm over 24 months after RT was used to define PD progression. After exome sequencing, SNPs associated with post-RT PD progression were identified by using logistic regression and homozygosity analyses. The web tools STRING, the Database for Annotation, Visualization and Integrated Discovery (DAVID), GeneCodis, and Ensembl Variant Effect Predictor were used for functional analysis.

RESULTS: Of the 48 patients with HNC with post-RT PD progression, 24 had no tooth with 5 mm or greater pocket depth before RT, whereas of the 21 patients with HNC without progression, 11 had PD initially. A total of 330 SNPs (249 genes) with over-represented homozygous genotype (98.5% variant allele) were found to be associated with post-RT PD. Sixty of these corresponded to PD-related pathways, including previously identified genes. In patients with HNC with post-RT PD progression, SNPs were found in genes (n = 10) in contrast to those without progression (n = 7).

CONCLUSIONS: The SNPs of collagen genes were identified, potentially defining susceptibility to PD in patients with HNC, and this could be further investigated to characterize PD drug targets.