Systematic Review of Genetic Polymorphisms Associated with Acute Pain and Relevant Acute Toxicities Induced by Radiotherapy for Head and Neck Cancer

Abstract

Background/objectivePain is the most common acute toxicity following radiation therapy (RT) for head and neck cancer (HNC). The multifactorial origin of radiotherapy-induced pain makes it highly challenging to manage in HNC patients. Multiple studies have been conducted to identify different germline genetic variants associated with cancer pain, however few of them focused on RT-induced acute pain. In this systematic review, we summarize potential mechanisms of acute pain after radiotherapy in HNC focusing on oral cavity/oropharyngeal cancer and identify genetic variants associated with radiotherapy-induced acute pain and other relevant acute toxicities.MethodsA comprehensive search of Ovid Medline, EMBASE and Web of Science databases using concepts and terms including “Variants”, “Polymorphisms”, “Radiotherapy”, “Acute pain”, “Acute toxicity” published up to February 28, 2022 was performed by two reviewers. Review articles and citations were reviewed manually. The reported SNPs associated with RT-induced acute pain and toxicities were reported, and the molecular function of the associated genes and pathways were described based on genetic annotation using The Human Gene Database; GeneCards.ResultsA total of 386 articles were identified electronically and an additional 8 articles were included after manual search. 39 articles were finally included. 51 variants were associated with 40 genes, of which 30 % had function in DNA damage response and repair, 25% in inflammatory and immune response, 17.5 % in cell death or cell cycle, and were associated with RT-inflammatory pain and acute mucositis or dermatitis. 4 variants in 4 genes were associated with neuropathy and neuropathic pain. 13 variants in 10 genes and were associated with RT-induced mixed types of post-RT-pain.ConclusionDifferent types of pain develop after RT, including inflammatory pain (acute mucositis and acute skin reaction); neuropathic pain; nociceptive pain; and mixed oral pain. Genetic variants involved in DNA damage response and repair, cell death, inflammation and neuropathic pathways may affect pain presentation post-RT. These variants could be used for acute pain prediction and personalized pain management in HNC patients receiving RT.