Isomura M, Oya N, Tachiiri S, Kaneyasu Y, Nishimura Y, Akimoto T, Hareyama M, Sugita T, Mitsuhashi N, Yamashita T, Aoki M, Sai H, Hirokawa Y, Sakata K, Karasawa K, Tomida A, Tsuruo T, Miki Y, Noda T, Hiraoka M, et al.
Clinical cancer research : an official journal of the American Association for Cancer Research. Date of publication 2008 Oct 15;volume 14(20):6683-9.
1. Clin Cancer Res. 2008 Oct 15;14(20):6683-9. doi: 10.1158/1078-0432.CCR-07-4389.
IL12RB2 and ABCA1 genes are associated with susceptibility to radiation
dermatitis.
Isomura M(1), Oya N, Tachiiri S, Kaneyasu Y, Nishimura Y, Akimoto T, Hareyama M,
Sugita T, Mitsuhashi N, Yamashita T, Aoki M, Sai H, Hirokawa Y, Sakata K,
Karasawa K, Tomida A, Tsuruo T, Miki Y, Noda T, Hiraoka M.
Author information:
(1)Genome Center, Japanese Foundation for Cancer Research, Japan.
PURPOSE: Severe acute radiation dermatitis is observed in approximately 5% to 10%
of patients who receive whole-breast radiotherapy. Several factors, including
treatment-related and patient-oriented factors, are involved in susceptibility to
severe dermatitis. Genetic factors are also thought to be related to a patient's
susceptibility to severe dermatitis. To elucidate genetic polymorphisms
associated with a susceptibility to radiation-induced dermatitis, a large-scale
single-nucleotide polymorphism (SNP) analysis using DNA samples from 156 patients
with breast cancer was conducted.
EXPERIMENTAL DESIGN: Patients were selected from more than 3,000 female patients
with early breast cancer who received radiotherapy after undergoing
breast-conserving surgery. The dermatitis group was defined as patients who
developed dermatitis at a National Cancer Institute Common Toxicity Criteria
grade of > or =2. For the SNP analysis, DNA samples from each patient were
subjected to the genotyping of 3,144 SNPs covering 494 genes.
RESULTS: SNPs that mapped to two genes, ABCA1 and IL12RB2, were associated with
radiation-induced dermatitis. In the ABCA1 gene, one of these SNPs was a
nonsynonymous coding SNP causing R219K (P = 0.0065). As for the IL12RB2 gene, the
strongest association was observed at SNP-K (rs3790568; P = 0.0013). Using
polymorphisms of both genes, the probability of severe dermatitis was estimated
for each combination of genotypes. These analyses showed that individuals
carrying a combination of genotypes accounting for 14.7% of the Japanese
population have the highest probability of developing radiation-induced
dermatitis.
CONCLUSION: Our results shed light on the mechanisms responsible for
radiation-induced dermatitis. These results may also contribute to the
individualization of radiotherapy.
DOI: 10.1158/1078-0432.CCR-07-4389
PMID: 18927311 [Indexed for MEDLINE]
