Polymorphisms in Radio-Responsive Genes and Its Association with Acute Toxicity among Head and Neck Cancer Patients

Abstract

Cellular and molecular approaches are being explored to find a biomarker which can predict the development of radiation induced acute toxicity prior to radiation therapy. SNPs in radiation responsive genes may be considered as an approach to develop tools for finding the inherited basis of clinical radiosensitivity. The current study attempts to screen single nucleotide polymorphisms/deletions in DNA damage response, DNA repair, profibrotic cytokine as well as antioxidant response genes and its predictive potential with the normal tissue adverse reactions from 183 head and neck cancer patients undergoing platinum based chemoradiotherapy or radiotherapy alone. We analysed 22 polymorphisms in 17 genes having functional relevance to radiation response. Radiation therapy induced oral mucositis and skin erythema was considered as end point for clinical radiosensitivity. Direct correlation of heterozygous and mutant alleles with acute reactions as well as haplotype correlation revealed NBN variants to be of predictive significance in analysing oral mucositis prior to radiotherapy. In addition, genetic linkage disequilibrium existed in XRCC1 polymorphisms for >grade 2 oral mucositis and skin reaction indicating the complex inheritance pattern. The current study indicates an association for polymorphism in NBN with normal tissue radiosensitivity and further warrants the replication of such studies in a large set of samples.

Management of oral and gastrointestinal mucosal injury: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up

“…Zinc supplements: The panel suggests that systemic zinc supplements administered orally may be of benefit to prevent oral mucositis in oral cancer patients receiving radiation therapy or chemoradiation (III). In recent years, research has increasingly demonstrated that patient-specific genetic characteristics are an important variable in determining risk and incidence of cancer therapy-related toxicity, including, but not limited to, oral mucosal injury [42][43][44]. It is now clear that genetic variation across individuals, including single nucleotide polymorphisms, is a key contributor to the toxicity trajectory for mucosal injury as well as for other toxicities caused by cancer therapies.…”

The Potential Effect of Oral Microbiota in the Prediction of Mucositis During Radiotherapy for Nasopharyngeal Carcinoma

“…Although it is hypothesized that genetic factors may correlate with an increased risk of developing mucositis (Venkatesh et al, 2014, Pratesi et al, 2011), the role of microorganisms in promoting inflammation and exacerbating mucositis still remains to be explored.…”

Association of GSTP1 and ERCC1 polymorphisms with toxicity in locally advanced head and neck cancer platinum‐based chemoradiotherapy treatment

“…Pratesi et al suggested that carriers of variant 135C allele had higher likelihood of developing dysphagia in HNC patients treated with RT . In contrast, other authors found no association . This gene participates in a common DNA damage response pathway associated with the activation of homologous recombination (HR) and double‐strand breaks (DSB) repair.…”

“…Various systematic reviews reported relationship between adverse RT effects in HNSCC and a range of candidate genes involved in DNA damage response and repair, oxidative stress response, or anti‐inflammatory response . This may account for the influence of cumulative effect of multiple genetic polymorphisms on the degree of toxicity induced by RT.…”