Abstract 4565: ATM genotyping modulates the risk of radiation-associated breast cancer among atomic-bomb survivors

Abstract

Abstract Objective: RERF epidemiological studies among atomic-bomb (A-bomb) survivors have demonstrated significantly-increased incidence of selected cancers with increased radiation dose. It is noteworthy that a great deal of inter-individual variation in susceptibility to radiation-associated cancers could not be explained solely by radiation dose and age at exposure, suggesting the possibility that this variation might be partly ascribed to inter-individual differences in DNA repair capacity. Of 11 known single nucleotide polymorphisms (SNPs) of the DNA repair gene ATM, we selected a particular SNP (rs189037; located in the 5′ untranslated region and therefore thought to be associated with ATM gene expression) and examined the association with radiation-associated breast cancer in the context of an RERF A-bomb survivor cohort study. Materials and Methods: A follow-up survey during 1981-2005 of 2,944 female members of the RERF Immunogenome Study Cohort identified a total of 100 breast cancer cases. ATM genotypes (ATM-G/G, -G/A, and -A/A) were determined by the TaqMan assay method for all cohort members. Relative risks (RRs) of breast cancer were estimated for radiation dose, the ATM genotypes, and the combined categories of dose levels and genotypes. Results and Discussion: Disregarding the genotype effects, RR of breast cancer significantly increased with increased radiation dose (RR = 1.51/Gy, 95% CI: 1.25-1.83). For overall radiation dose levels, A-bomb survivors with ATM-G/G homozygote revealed a significantly-increased RR of breast cancer (RR = 1.85, 95%CI: 1.24-2.75), using as reference the risk of those with ATM-A/A homozygotes combined with ATM-G/A heterozygotes. When radiation dose was categorized into three levels (< 5 mGy referred to as “non-exposed,” 5-530 mGy, and >530 mGy), the survivors with ATM-A/A who were exposed to the highest dose level (>530 mGy) showed the highest risk of breast cancer (RR = 4.76, 95%CI: 2.30-9.88), using as reference the risk of “non-exposed” survivors with ATM-T/T or ATM-A/T. These results suggest the possibility that the ATM genotyping may be involved in individually differing susceptibility to radiation-associated breast cancer. Citation Format: Tomonori Hayashi, Yiqun Hu, Kengo Yoshida, Waka Ohishi, Ayumi Hida, Ikue Hayashi, Seishi Kyoizumi, Yoichiro Kusunoki, Kei Nakachi. ATM genotyping modulates the risk of radiation-associated breast cancer among atomic-bomb survivors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4565. doi:10.1158/1538-7445.AM2015-4565