Expressive

rs1131769 (STING1): Radiotherapy Mucositis Risk

Key takeaways

  • The C allele of rs1131769 is associated with approximately 95% higher odds of mucositis after head and neck cancer radiotherapy (pooled OR = 1.95)
  • The association was replicated across three independent cohorts (Danish, Dutch, and Asian) with a pooled p-value of 4.34 x 10^-16
  • The variant sits near STING1 on chromosome 5, a region linked to altered expression of multiple nearby genes in GTEx data
  • GTEx data shows expression effects in brain, lung, esophagus, skin, adrenal gland, and immune cells
  • This was the first GWAS of radiotherapy toxicity specifically in European laryngeal and oro/hypopharyngeal cancer patients

Key takeaways

  • The C allele of rs1131769 is associated with approximately 95% higher odds of mucositis after head and neck cancer radiotherapy (pooled OR = 1.95)
  • The association was replicated across three independent cohorts (Danish, Dutch, and Asian) with a pooled p-value of 4.34 x 10^-16
  • The variant sits near STING1 on chromosome 5, a region linked to altered expression of multiple nearby genes in GTEx data
  • GTEx data shows expression effects in brain, lung, esophagus, skin, adrenal gland, and immune cells
  • This was the first GWAS of radiotherapy toxicity specifically in European laryngeal and oro/hypopharyngeal cancer patients

What the research says A two-stage genome-wide association study (GWAS) of 1780 European head and neck cancer (HNC) patients identified a locus on chromosome 5 near STING1 as strongly associated with mucositis, an inflammation and ulceration of the mucous membranes lining the mouth and throat, following radiotherapy treatment. The C allele of rs1131769 at this locus carried a pooled odds ratio (OR) of 1.95 (95% CI 1.48-2.41; p = 4.34 x 10^-16) in meta-analysis, meaning carriers had approximately 95% higher odds of developing this complication. The finding was first identified in 1183 Danish patients, then replicated in 597 Dutch patients, and further validated in 235 Asian nasopharyngeal cancer patients.

Reported associations

  • Radiotherapy-induced mucositis in head and neck cancer: The C allele was associated with approximately 95% higher odds of mucositis after radiotherapy (pooled OR = 1.95, 95% CI 1.48-2.41, p = 4.34 x 10^-16) in meta-analysis of 1780 European HNC patients, with directional consistency also observed in an Asian validation cohort of 235 nasopharyngeal cancer patients

Evidence quality The discovery cohort comprised 1183 Danish HNC patients (DAHANCA protocols); the replication cohort comprised 597 Dutch HNC patients; and 235 Asian nasopharyngeal cancer patients provided further validation. The pooled p-value of 4.34 x 10^-16 is highly significant, and the association was directionally consistent across all three independent cohorts. However, the Asian validation cohort differed in primary tumour site (nasopharynx versus larynx or oro/hypopharynx in the European cohorts), limiting direct cross-population comparability. The authors describe this as the first exploratory GWAS of radiotherapy-induced toxicity in European laryngeal and oro/hypopharyngeal HNC patients, and call for a larger Meta-GWAS to identify further risk variants. Functional mechanisms underlying this association have not yet been established by the cited study.

Tissue-specific expression effects

  • DNAJC18: Reduced expression in adrenal gland and in EBV-transformed lymphocytes (an immune cell type) GTEx Portal
  • PROB1: Increased expression in two brain regions (putamen basal ganglia and anterior cingulate cortex), as well as in lung and esophagus mucosa GTEx Portal
  • SLC23A1: Reduced expression in sun-exposed skin of the lower leg GTEx Portal
  • ENSG00000302512: Reduced expression in subcutaneous adipose (under-skin fat) tissue GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs1131769 and which gene is it near?

rs1131769 is a genetic variant on chromosome 5, located near the STING1 gene. Research in head and neck cancer patients has linked the C allele of this variant to substantially higher odds of developing mucositis, a painful inflammation of the mouth and throat lining, following radiotherapy.

What effect does the C allele of rs1131769 have on mucositis risk in research studies?

In a meta-analysis of 1780 European head and neck cancer patients, the C allele was associated with an odds ratio of 1.95 (95% CI 1.48-2.41), meaning carriers had approximately 95% higher odds of developing mucositis after radiotherapy. This pattern was directionally consistent across independent European and Asian patient cohorts.

What is mucositis in head and neck cancer treatment?

Mucositis is a painful inflammation and ulceration of the mucous membranes lining the mouth and throat. It is a significant side effect of radiotherapy for head and neck cancers and one of the primary toxicity endpoints studied in radiogenomics research.

How strong is the evidence linking rs1131769 to mucositis?

The association reached a pooled p-value of 4.34 x 10^-16 in meta-analysis, which is highly significant. The finding was identified in a Danish discovery cohort, replicated in a Dutch cohort, and further supported in an Asian nasopharyngeal cancer cohort, though the Asian cohort had a different primary tumour site, limiting direct comparability.

Does rs1131769 affect gene expression in other tissues?

GTEx data shows this variant is linked to reduced expression of DNAJC18 in adrenal gland and immune cells, increased expression of PROB1 in brain regions and lung, and reduced expression of SLC23A1 in skin. The clinical relevance of these expression changes has not been established.