Unexpectedly severe acute radiotherapy side effects are associated with single nucleotide polymorphisms of the melanocortin-1 receptor

Fogarty, Gerald B., Muddle, Rory, Sprung, Carl N., Chen, Wei, Duffy, David, Sturm, Richard A. and McKay, Michael J. (2010) Unexpectedly severe acute radiotherapy side effects are associated with single nucleotide polymorphisms of the melanocortin-1 receptor. International Journal of Radiation: Oncology - Biology - Physics, 77 5: 1486-1492. doi:10.1016/j.ijrobp.2009.07.1690


Author Fogarty, Gerald B.
Muddle, Rory
Sprung, Carl N.
Chen, Wei
Duffy, David
Sturm, Richard A.
McKay, Michael J.
Title Unexpectedly severe acute radiotherapy side effects are associated with single nucleotide polymorphisms of the melanocortin-1 receptor
Journal name International Journal of Radiation: Oncology - Biology - Physics   Check publisher's open access policy
ISSN 0360-3016
1879-355X
0145-1464
Publication date 2010-07-01
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.ijrobp.2009.07.1690
Open Access Status Not Open Access
Volume 77
Issue 5
Start page 1486
End page 1492
Total pages 7
Editor James D. Cox
Place of publication Philadelphia, United States
Publisher Elsevier
Language eng
Subject C1
920102 Cancer and Related Disorders
060103 Cell Development, Proliferation and Death
060405 Gene Expression (incl. Microarray and other genome-wide approaches)
Formatted abstract
Purpose: The melanocortin-1 receptor (MC1R) regulates melanin biogenesis. Deoxyribonucleic acid sequence variants
in the form of single nucleotide polymorphisms (SNPs) of MC1R affect melanin expression and are linked to
skin phenotype.We aimed to determine whether SNPs of MC1R were associated with unexpectedly severe ionizing
radiation reactions.
Methods and Materials: The MC1R genotype of a cohort of Australians with unexpectedly severe acute and/or late
reactions (Common Terminology Criteria Version 3 (CTCv3) Grade 3 or 4) to radiotherapy (RT) for cancer (n = 30)
was analyzed. The findings were compared with control data from our previous study of MC1R representative of
the general Australian population (n = 1,787).
Results: The difference in frequency of alleles encoding a ‘‘red hair color’’ phenotype in the cohort of patients with
unexpectedly severe acute radiation reactions (n = 12) was significantly increased compared with the control population
(p = 0.003). Acute radiosensitivity was especially associated with the R160W variant allele (odds ratio, 3.64
[95% confidence interval, 1.3–10.27]). The corresponding comparison of MC1R controls with unexpectedly severe
late radiation reactions (n = 18) was not significant. It was also found that R160W as a part of the genotype in the
patients with unexpectedly severe acute RT side effects as compared with the control group was also significant
(p = 0.043).
Conclusions: In this small cohort of cancer patients, deoxyribonucleic acid sequence variants of the MC1R gene,
especially the R160W variant, have been associated with unexpectedly severe acute reactions to RT. This result
needs to be verified in a larger cohort of patients. © 2010 Elsevier Inc.
Keyword Acute radiation reaction
MC1R
Single nucleotide polymorphisms
R160W
Predictive assays
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 24 November 2009.

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
 
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Created: Wed, 24 Feb 2010, 20:51:25 EST by Susan Allen on behalf of Institute for Molecular Bioscience