Genetic Variants in CD44 and MAT1A Confer Susceptibility to Acute Skin Reaction in Breast Cancer Patients Undergoing Radiation Therapy

Mumbrekar, Kamalesh Dattaram and Rao, Satish BS and Kabekkodu, Shama Prasada and Fernandes, Donald J and Satyamoorthy, K (2016) Genetic Variants in CD44 and MAT1A Confer Susceptibility to Acute Skin Reaction in Breast Cancer Patients Undergoing Radiation Therapy. International Journal of Radiation Oncology, Biology, Physics, 97 (1). pp. 118-127. ISSN 0360-3016

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Abstract

Purpose: Heterogeneity in radiation therapy (RT)-induced normal tissue toxicity is observed in 10% of cancer patients, limiting the therapeutic outcomes. In addition to treatment-related factors, normal tissue adverse reactions also manifest from genetic alterations in distinct pathways majorly involving DNA damageerepair genes, inflammatory cytokine genes, cell cycle regulation, and antioxidant response. Therefore, the common sequence variants in these radioresponsive genes might modify the severity of normal tissue toxicity, and the identification of the same could have clinical relevance as a predictive biomarker.Methods and Materials: The present study was conducted in a cohort of patients with breast cancer to evaluate the possible associations between genetic variants in radioresponsive genes described previously and the risk of developing RT-induced acute skin adverse reactions. We tested 22 genetic variants reported in 18 genes (ie,NFE2L2, OGG1, NEIL3, RAD17, PTTG1, REV3L, ALAD, CD44, RAD9A, TGFbR3,MAD2L2, MAP3K7, MAT1A, RPS6KB2, ZNF830, SH3GL1, BAX, and XRCC1) using TaqMan assay-based real-time polymerase chain reaction. At the end of RT, the severity of skin damage was scored, and the subjects were dichotomized as nonoverresponders (Radiation Therapy Oncology Group grade <2) and overresponders (Radiation Therapy Oncology Group grade �2) for analysis.Results: Of the 22 single nucleotide polymorphisms studied, the rs8193 polymorphism lying in the micro-RNA binding site of 30-UTR of CD44 was significantly (PZ.0270) associated with RT-induced adverse skin reactions. Generalized multifactor dimensionality reduction analysis showed significant (PZ.0107) geneegene interactions between MAT1A and CD44. Furthermore, an increase in the total number of risk alleles was associated with increasing occurrence of overresponses (PZ.0302).Conclusions: The genetic polymorphisms in radioresponsive genes act as genetic modifiers of acute normal tissue toxicity outcomes after RT by acting individually (rs8193), by geneegene interactions (MAT1A and CD44), and/or by the additive effects of risk alleles.

Item Type: Article
Uncontrolled Keywords: Radiotherpy; Breast cancer; Normal tissue toxicity; SNP
Subjects: Life Sciences > MLSC Manipal
Medicine > KMC Manipal > Radiotherapy and Oncology
Depositing User: KMC Library
Date Deposited: 03 Jan 2017 14:52
Last Modified: 03 Jan 2017 14:52
URI: http://eprints.manipal.edu/id/eprint/147860

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