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Genomic determinants of normal tissue toxicity after radiotherapy for head and neck malignancy: a systematic review

Ghazali, Naseem; Shaw, Richard J; Rogers, Simon N and Risk, Janet M (2012) Genomic determinants of normal tissue toxicity after radiotherapy for head and neck malignancy: a systematic review. Oral Oncology, 48 (11). pp. 1090-1100. ISSN 1368-8375

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Abstract

Interindividual variations in radiotoxicity responses exist despite uniform treatment protocols. It is speculated that normal genetic variants, particularly single nucleotide polymorphisms (SNPs) may influence normal head and neck (HN) tissue radiotoxicity. This first-ever systematic review was undertaken to evaluate the association of SNPs with normal HN tissues radiotoxicity. Multiple databases (1950–February 2012) were reviewed using a combination of related keywords and MeSH terms. All published HN radiotoxicity studies with sufficient relevant data for extraction were included. The outcomes evaluated were acute and late radiotoxicity endpoints. Methodological quality assessment based on the STrengthening the REporting of Genetic Association (STREGA) statement was performed. Seven articles from 692 articles searched fulfilled the eligibility criteria. Recruited sample sizes were small (range, 32–140). There were 5/7 case-control studies. All studies used multimodality treatment with heterogeneous radiation parameters. Candidate gene approach was used in all studies. Fourteen SNPs from 9 genes were evaluated from the following pathways: DNA damage response, radiation fibrogenesis and oxidative/xenobiotic metabolism. Acute radiotoxicity events were associated with SNPs of DNA repair genes (OR, 3.01–4.08). SNPs of TGFb1 were associated with osteoradionecrosis (OR, 4.2) and subcutaneous fibrosis. Genetic association studies in HN radiotoxicity currently provide hypothesis-generating findings that require validation in larger studies. Future studies must incorporate critical methodological issues and technological improvements, including using a genome-wide approach. Headway is possible through case-pooling of existing clinical trial data which could create a larger sample size of well-characterized treatment and endpoints. Also, on-going HN cancer clinical trials should consider extending their toxicity evaluation to include genetic association studies.

Item Type:Article
Additional Information:Available online 29 August 2012. Issue: November, 2012.
Uncontrolled Keywords:oral cancer; radiosensitivity; Genetic association study; Genetic polymorphism; Head and neck cancer; Radiotherapy; Radiotoxicity; Single nucleotide polymorphism; Toxicity
Subjects:R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Departments, Research Centres and Related Units:Academic Faculties, Institutes and Research Centres > Faculty of Medicine > School of Cancer Studies
DOI:10.1016/j.oraloncology.2012.08.002
Related URLs:
Refereed:Yes
Status:Published
ID Code:7697
Deposited On:10 Oct 2012 15:35
Last Modified:28 Feb 2013 16:46

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