title: 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.
authors.affiliation: Division of Radiobiology & Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka, India.
authors.forename: Goutham Hassan
authors.initials: GH
authors.lastname: Venkatesh
authors.affiliation: Manipal Hospital, Bangalore, Karnataka, India.
authors.forename: Vadhiraja Bejadi
authors.initials: VB
authors.lastname: Manjunath
authors.affiliation: Division of Radiobiology & Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka, India.
authors.forename: Kamalesh Dattaram
authors.initials: KD
authors.lastname: Mumbrekar
authors.affiliation: Division of Biotechnology, School of Life Sciences, Manipal University, Manipal, Karnataka, India.
authors.forename: Hitendra
authors.initials: H
authors.lastname: Negi
authors.affiliation: Department of Radiotherapy & Oncology, Shiridi SaiBaba Cancer Hospital and Research Centre, Kasturba Hospital, Manipal, Karnataka, India.
authors.forename: Donald Jerard
authors.initials: DJ
authors.lastname: Fernandes
authors.affiliation: Department of Radiotherapy & Oncology, Shiridi SaiBaba Cancer Hospital and Research Centre, Kasturba Hospital, Manipal, Karnataka, India.
authors.forename: Krishna
authors.initials: K
authors.lastname: Sharan
authors.affiliation: Department of Radiotherapy & Oncology, Kasturba Medical College and Hospital, Mangalore, Karnataka, India.
authors.forename: Sourjya
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Division of Radiobiology & Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka, India.
authors.forename: Satish Rao
authors.initials: SR
authors.lastname: Bola Sadashiva
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D059248:Chemoradiotherapy / Q000009:adverse effects*; D015986:Confounding Factors, Epidemiologic; D003710:Demography; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D012307:Risk Factors