Genetic Susceptibility to Patient-Reported Xerostomia Among Long-Term Oropharyngeal Cancer Survivors

Authors

Puja Aggarwal
Katherine A Hutcheson
Robert Yu
Jian Wang
Clifton D Fuller
Adam S Garden
Ryan P Goepfert
Jillian Rigert
Frank E Mott
Charles Lu
Stephen Y Lai
G Brandon Gunn
Mark S Chambers
Guojun Li
Chih-Chieh Wu
Ehab Y Hanna
Erich M Sturgis
Sanjay Shete

Publication Date

4-22-2022

Journal

Scientific Reports

DOI

10.1038/s41598-022-10538-9

PMID

35459784

PMCID

PMC9033773

PubMedCentral® Posted Date

4-22-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Cancer Survivors, Genetic Predisposition to Disease, Head and Neck Neoplasms, Humans, Microfilament Proteins, Oropharyngeal Neoplasms, Patient Reported Outcome Measures, Receptors, Cell Surface, Xerostomia, Genetics, Genetic association study, Genome-wide association studies

Abstract

Genetic susceptibility for xerostomia, a common sequela of radiotherapy and chemoradiotherapy for head and neck cancer, is unknown. Therefore, to identify genetic variants associated with moderate to severe xerostomia, we conducted a GWAS of 359 long-term oropharyngeal cancer (OPC) survivors using 579,956 autosomal SNPs. Patient-reported cancer treatment-related xerostomia was assessed using the MD Anderson Symptom Inventory. Patient response was dichotomized as moderate to severe or none to mild symptoms. In our study, 39.2% of OPC survivors reported moderate to severe xerostomia. Our GWAS identified eight SNPs suggestively associated with higher risk of moderate to severe xerostomia in six genomic regions (2p13.3, rs6546481, Minor Allele (MA) = A, ANTXR1, P = 4.3 × 10–7; 5p13.2–p13.1, rs16903936, MA = G, EGFLAM, P = 5.1 × 10–6; 4q21.1, rs10518156, MA = G, SHROOM3, P = 7.1 × 10–6; 19q13.42, rs11882068, MA = G, NLRP9, P = 1.7 × 10–5; 12q24.33, rs4760542, MA = G, GLT1D1, P = 1.8 × 10–5; and 3q27.3, rs11714564, MA = G, RTP1, P = 2.9 × 10–5. Seven SNPs were associated with lower risk of moderate to severe xerostomia, of which only one mapped to specific genomic region (15q21.3, rs4776140, MA = G, LOC105370826, a ncRNA class RNA gene, P = 1.5 × 10–5). Although our small exploratory study did not reach genome-wide statistical significance, our study provides, for the first time, preliminary evidence of genetic susceptibility to xerostomia. Further studies are needed to elucidate the role of genetic susceptibility to xerostomia.