2637

Abstract

Purpose/Objective(s)To determine the single nucleotide polymorphisms (SNPs) associated with radiation induced dermatitis, a large scale SNP analysis was conducted using peripheral lymphocytes of patients who underwent whole breast radiotherapy following breast conserving surgery.Materials/MethodsThis is a multi-institutional case-control study comprehensively analyzing SNPs and comparing the alleles between the patients who developed >= grade 2 dermatitis (dermatitis group; n = 77) and the control patients (control group; n = 79). The patients of the dermatitis group were selected from the pool of more than 3,000 patients, reviewing the photographs of the skin and the radiation dose distribution charts, to exclude the confounding external factors. In patient selection for the control group, the patient-to-patient matching was employed, so that the two groups should be well balanced in terms of the major patient characteristics (e.g. patient’s age, menopausal status and pathological T/N classifications) and the therapeutic parameters (e.g. the institution, beam energy, radiation dose and fractionation). For the SNP analysis, DNA from each patient was subjected to genotyping of 3,144 SNPs covering 487 genes.ResultsTwo loci, the IL12RB2 gene locus and the ABCA1 gene locus, were shown to be associated with dermatits. In IL12RB2 gene, 5 SNPs of examined 13 SNPs showed significant correlation with dermatitis (p = 0.0060 at lowest). The haplotype block analysis indicated that all of these 5 SNPs were located in a single haplotype block. A haplotype designated as H3 was associated with dermatisis (p=0.004). As for ABCA1 gene, 50 SNPs were examined and 8 SNPs showed significant correlation with dermatitis (p = 0.0038 at lowest). One of them was a cSNP causing amino acid substitution between Lys and Arg at the 219th amino acid. The haplotype block analysis revealed that the 8 SNPs were located in 2 haplotype blocks.ConclusionsThe present study featured a more comprehensive SNPs analysis than any previous study. Since a considerable part of clinically observed hyperradiosensitivity may be regulated by integration of multiple minor alterations in genetic function, a comprehensive analysis, as was performed in the present study, may be suitable for identification of radiosensitive population of patients. We concluded that several SNPs in IL12RB2 and ABCA1 genes were associated with susceptibility of radiation induced dermatitis. This was suggested to be a non-random event, considering that these SNPs were located only in one or two haplotype blocks of the genes. Analyzing these SNPs may be a promising predictive assay to identify the radiosensitive patients, and to individualize radiotherapy. Purpose/Objective(s)To determine the single nucleotide polymorphisms (SNPs) associated with radiation induced dermatitis, a large scale SNP analysis was conducted using peripheral lymphocytes of patients who underwent whole breast radiotherapy following breast conserving surgery. To determine the single nucleotide polymorphisms (SNPs) associated with radiation induced dermatitis, a large scale SNP analysis was conducted using peripheral lymphocytes of patients who underwent whole breast radiotherapy following breast conserving surgery. Materials/MethodsThis is a multi-institutional case-control study comprehensively analyzing SNPs and comparing the alleles between the patients who developed >= grade 2 dermatitis (dermatitis group; n = 77) and the control patients (control group; n = 79). The patients of the dermatitis group were selected from the pool of more than 3,000 patients, reviewing the photographs of the skin and the radiation dose distribution charts, to exclude the confounding external factors. In patient selection for the control group, the patient-to-patient matching was employed, so that the two groups should be well balanced in terms of the major patient characteristics (e.g. patient’s age, menopausal status and pathological T/N classifications) and the therapeutic parameters (e.g. the institution, beam energy, radiation dose and fractionation). For the SNP analysis, DNA from each patient was subjected to genotyping of 3,144 SNPs covering 487 genes. This is a multi-institutional case-control study comprehensively analyzing SNPs and comparing the alleles between the patients who developed >= grade 2 dermatitis (dermatitis group; n = 77) and the control patients (control group; n = 79). The patients of the dermatitis group were selected from the pool of more than 3,000 patients, reviewing the photographs of the skin and the radiation dose distribution charts, to exclude the confounding external factors. In patient selection for the control group, the patient-to-patient matching was employed, so that the two groups should be well balanced in terms of the major patient characteristics (e.g. patient’s age, menopausal status and pathological T/N classifications) and the therapeutic parameters (e.g. the institution, beam energy, radiation dose and fractionation). For the SNP analysis, DNA from each patient was subjected to genotyping of 3,144 SNPs covering 487 genes. ResultsTwo loci, the IL12RB2 gene locus and the ABCA1 gene locus, were shown to be associated with dermatits. In IL12RB2 gene, 5 SNPs of examined 13 SNPs showed significant correlation with dermatitis (p = 0.0060 at lowest). The haplotype block analysis indicated that all of these 5 SNPs were located in a single haplotype block. A haplotype designated as H3 was associated with dermatisis (p=0.004). As for ABCA1 gene, 50 SNPs were examined and 8 SNPs showed significant correlation with dermatitis (p = 0.0038 at lowest). One of them was a cSNP causing amino acid substitution between Lys and Arg at the 219th amino acid. The haplotype block analysis revealed that the 8 SNPs were located in 2 haplotype blocks. Two loci, the IL12RB2 gene locus and the ABCA1 gene locus, were shown to be associated with dermatits. In IL12RB2 gene, 5 SNPs of examined 13 SNPs showed significant correlation with dermatitis (p = 0.0060 at lowest). The haplotype block analysis indicated that all of these 5 SNPs were located in a single haplotype block. A haplotype designated as H3 was associated with dermatisis (p=0.004). As for ABCA1 gene, 50 SNPs were examined and 8 SNPs showed significant correlation with dermatitis (p = 0.0038 at lowest). One of them was a cSNP causing amino acid substitution between Lys and Arg at the 219th amino acid. The haplotype block analysis revealed that the 8 SNPs were located in 2 haplotype blocks. ConclusionsThe present study featured a more comprehensive SNPs analysis than any previous study. Since a considerable part of clinically observed hyperradiosensitivity may be regulated by integration of multiple minor alterations in genetic function, a comprehensive analysis, as was performed in the present study, may be suitable for identification of radiosensitive population of patients. We concluded that several SNPs in IL12RB2 and ABCA1 genes were associated with susceptibility of radiation induced dermatitis. This was suggested to be a non-random event, considering that these SNPs were located only in one or two haplotype blocks of the genes. Analyzing these SNPs may be a promising predictive assay to identify the radiosensitive patients, and to individualize radiotherapy. The present study featured a more comprehensive SNPs analysis than any previous study. Since a considerable part of clinically observed hyperradiosensitivity may be regulated by integration of multiple minor alterations in genetic function, a comprehensive analysis, as was performed in the present study, may be suitable for identification of radiosensitive population of patients. We concluded that several SNPs in IL12RB2 and ABCA1 genes were associated with susceptibility of radiation induced dermatitis. This was suggested to be a non-random event, considering that these SNPs were located only in one or two haplotype blocks of the genes. Analyzing these SNPs may be a promising predictive assay to identify the radiosensitive patients, and to individualize radiotherapy.