title: Haplotype-based analysis of genes associated with risk of adverse skin reactions after radiotherapy in breast cancer patients.
abstract: OBJECTIVE
  To identify haplotypes of single nucleotide polymorphism markers associated with the risk of early adverse skin reactions (EASRs) after radiotherapy in breast cancer patients.
  
  
  METHODS
  DNA was sampled from 399 Japanese breast cancer patients who qualified for breast-conserving radiotherapy. Using the National Cancer Institute-Common Toxicity Criteria scoring system, version 2, the patients were grouped according to EASRs, defined as those occurring within 3 months of starting radiotherapy (Grade 1 or less, n = 290; Grade 2 or greater, n = 109). A total of 999 single nucleotide polymorphisms from 137 candidate genes for radiation susceptibility were genotyped, and the haplotype associations between groups were assessed.
  
  
  RESULTS
  The global haplotype association analysis (p < 0.05 and false discovery rate < 0.05) indicated that estimated haplotypes in six loci were associated with EASR risk. A comparison of the risk haplotype with the most frequent haplotype in each locus showed haplotype GGTT in CD44 (odds ratio [OR] = 2.17; 95% confidence interval [CI], 1.07-4.43) resulted in a significantly greater EASR risk. Five haplotypes, CG in MAD2L2 (OR = 0.55; 95% CI, 0.35-0.87), GTTG in PTTG1 (OR = 0.48; 95% CI, 0.24-0.96), TCC (OR = 0.48; 95% CI, 0.26-0.89) and CCG (OR = 0.50; 95% CI, 0.27-0.92) in RAD9A, and GCT in LIG3 (OR = 0.46; 95% CI, 0.22-0.93) were associated with a reduced EASR risk. No significant risk haplotype was observed in REV3L.
  
  
  CONCLUSIONS
  Individual radiosensitivity can be partly determined by these haplotypes in multiple loci. Our findings may lead to a better understanding of the mechanisms underlying the genetic variation in radiation sensitivity and resistance among breast cancer patients.
authors: RadGenomics Project, National Institute of Radiological Sciences, Chiba, Japan.
authors: Tomo
authors: T
authors: Suga
authors: Atsuko
authors: A
authors: Ishikawa
authors: Masakazu
authors: M
authors: Kohda
authors: Yoshimi
authors: Y
authors: Otsuka
authors: Shigeru
authors: S
authors: Yamada
authors: Naohito
authors: N
authors: Yamamoto
authors: Yuta
authors: Y
authors: Shibamoto
authors: Yoshihiro
authors: Y
authors: Ogawa
authors: Kuninori
authors: K
authors: Nomura
authors: Keizen
authors: K
authors: Sho
authors: Motoko
authors: M
authors: Omura
authors: Kenji
authors: K
authors: Sekiguchi
authors: Yuzo
authors: Y
authors: Kikuchi
authors: Yuichi
authors: Y
authors: Michikawa
authors: Shuhei
authors: S
authors: Noda
authors: Masashi
authors: M
authors: Sagara
authors: Jun
authors: J
authors: Ohashi
authors: Shinji
authors: S
authors: Yoshinaga
authors: Junetsu
authors: J
authors: Mizoe
authors: Hirohiko
authors: H
authors: Tsujii
authors: Mayumi
authors: M
authors: Iwakawa
authors: Takashi
authors: T
authors: Imai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000532:radiotherapy; D016009:Chi-Square Distribution; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011832:Radiation Injuries / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D012867:Skin / Q000528:radiation effects*
chemical_list: D005819:Genetic Markers