Genetic susceptibility to patient-reported xerostomia among long-term oropharyngeal cancer survivors

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.