title: Unexpectedly severe acute radiotherapy side effects are associated with single nucleotide polymorphisms of the melanocortin-1 receptor.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Division of Radiation Oncology and Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Gerald.fogarty@i-med.com.au
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Fogarty
authors.forename: Rory
authors.initials: R
authors.lastname: Muddle
authors.forename: Carl N
authors.initials: CN
authors.lastname: Sprung
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: David
authors.initials: D
authors.lastname: Duffy
authors.forename: Richard A
authors.initials: RA
authors.lastname: Sturm
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McKay
mesh_terms: D000208:Acute Disease; D000483:Alleles; D001315:Australia; D016022:Case-Control Studies; D015331:Cohort Studies; D016001:Confidence Intervals; D006200:Hair Color / Q000235:genetics*; D006801:Humans; D008543:Melanins / Q000096:biosynthesis*; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011832:Radiation Injuries / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D012880:Skin Pigmentation / Q000235:genetics*
chemical_list: D008543:Melanins; D044102:Receptor, Melanocortin, Type 1