BRIEF REPORT Genetic predisposition to radiation induced sarcoma: possible role for BRCA and p53 mutations Luna Kadouri • Michal Sagi • Yael Goldberg • Israela Lerer • Tamar Hamburger • Tamar Peretz Received: 9 April 2013 / Accepted: 21 June 2013 / Published online: 4 July 2013 Ó Springer Science+Business Media New York 2013 Abstract The estimated incidence of radiation-associated sarcoma (RAS) is 0.03–0.2 % in 5 years post treatment. Most cancer predisposing genes are involved in DNA repair; therefore, elevated RAS risk in these patients is plausible. Cases of angiosarcoma post breast cancer treat- ment were reported in BRCA1 and BRCA2 carriers. We report the genetic evaluation of seven cases with suspected RAS from patients counseled in our cancer-genetic clinic. Of 2,885 breast cancer patient, 470 were BRCA1 or two mutation carriers and three were p53 mutation carriers. Of them seven developed sarcoma in the field of irradiation; five in the chest wall and two in other sites. Genetic evaluation revealed BRCA1 mutation in two, BRCA2 mutation in additional patient and a carrier of p53 muta- tion. The estimation of risk for RAS in patients with genetic predisposition is limited due to the rarity of this event, and the bias in referral to the clinic toward younger age. With these limitations the rate of RAS is 0.43 % (2/ 470, 95 % CI -0.17 to 1.02, SE = 0.3) in this group in a median follow-up of 8.2 years (range 1 month to 51 years). If we assume irradiation for the breast in 80 % of the patients than rate of RAS in group is proximately 0.53 % (2/376, 95 % CI -0.21 to 1.26, SE = 0.37). A BRCA1 carrier which had sarcoma after irradiation to head and neck carcinoma was not included in these analyses. In conclusion, we found a high frequency of BRCA1/2 mutation among our patients diagnosed with RAS. However, we estimated approximately twofold increase in the risk of RAS in BRCA1/2 carriers which was not sig- nificant compared to reports in general population. There- fore, RAS is a rare event in BRCA carriers as in the general population, and should not be considered in the decision regarding irradiation treatment in this population. Keywords BRCA1 Á BRCA2 Á p53 Á Radiation-associated sarcoma Introduction Post-radiation sarcoma is a rare event with estimated incidence that ranges from 0.03 to 0.2 % in patients which survived 5 years after treatment [1]. The latency period ranges from 2 to 3 years to up to 50 years and the chest wall and pelvis are the most frequent sites due to the fre- quency of the antecedent tumors; breast and gynecologic cancers, which are often treated with irradiation. Both sites are also associated with high median survival, which allow the development of sarcoma. Although a large range of doses of radiation have been reported, evidence suggests dose–response dependence [1]. The etiology of post-radiation sarcoma is related to double-stranded DNA damage induced by radiation which results in genome instability that may lead to sarcoma. The combination with chemotherapeutic agents such as alkyl- ating agents may elevate the risk as was found in large cohorts of childhood cancer survivors [2, 3]. Molecular studies of radiation-associated sarcomas (RAS) revealed common inactivation of p53 pathway [4] and characteristic alterations in CGH assays [5]. Frequent amplification of cMyc was found in radiation-induced angiosarcoma but not in other RAS [6]. L. Kadouri (&) Á Y. Goldberg Á T. Hamburger Á T. Peretz Sharett Institute of Oncology, Hadassah Medical Center, Hebrew University, 91120 Jerusalem, Israel e-mail: luna@hadassah.org.il M. Sagi Á I. Lerer Department of Human Genetics, Hadassah Medical Center, Hebrew University, Jerusalem, Israel 123 Breast Cancer Res Treat (2013) 140:207–211 DOI 10.1007/s10549-013-2621-z