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IL12RB2 and ABCA1 Genes Are Associated with Susceptibility to Radiation Dermatitis

Authors' Affiliations: ¹ Genome Center, Japanese Foundation for Cancer Research; ² Department of Radiology, Tokyo Women's Medical University, School of Medicine; ³ Department of Radiation Oncology, Cancer Institute Hospital; ⁴ Department of Radiology, School of Medicine, Juntendo University; ⁵ Institute of Molecular and Cellular Biosciences, The University of Tokyo; ⁶ Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan; ⁷ Department of Radiation Oncology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; ⁸ Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan; ⁹ Department of Radiology, Hiroshima University, Hiroshima, Japan; ¹⁰ Department of Radiation Oncology, Kinki University School of Medicine, Osaka, Japan; ¹¹ Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan; ¹² Department of Radiology, Sapporo Medical University, School of Medicine, Sapporo, Japan; ¹³ Department of Radiology, Niigata Cancer Center Hospital; ¹⁴ Department of Radiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; and ¹⁵ Department of Radiology, Hirosaki University School of Medicine, Hirosaki, Japan

Requests for reprints: Yoshio Miki, Genome Center, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo 135-8550, Japan. Phone: 81-3-3570-0453; Fax: 81-3-3570-0454; E-mail: miki{at}jfcr.or.jp.

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 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.