Abstract 1849: Occurrence of childhood tumors in relatives of childhood cancer patients

Abstract Background: Increased susceptibility for childhood tumors, mainly associated with known syndromes, has been found among siblings. Occurrence of childhood cancer in more distant relatives of childhood cancer patients seems to be less frequently investigated. In this study we evaluated the occurrence of childhood cancer among relatives of childhood cancer patients. Evaluation for occurrence of known syndromes and screening for p53 mutations was performed in families with more than one childhood cancer case. Methods: The history of childhood cancer among first- to third degree relatives was evaluated for 196 patients, diagnosed with childhood cancer between 1962 and 2009, where both DNA and the family history of cancer was available. Most of these patients were diagnosed after 1985. Family history of cancer was collected using a standardized self-administered questionnaire which also included a question about occurrence of cancer in more distant relatives. When possible, verification of reported cases of childhood tumors was obtained from medical records or the Cancer Registry of South Sweden. Screening for p53 mutations in blood from the proband, was performed using direct sequencing. Results: A total number of 18 (9.2 %) patients reported occurrence of a childhood tumor among relatives. In 3 (1.5 %) cases the affected child was a first degree relative, in another 3 (1.5 %) cases a second degree relative, in 5 (2.6 %) cases a third degree relative and in 7 (3.6 %) cases the childhood tumor occurred in a fourth- or higher degree relative. One patient reported occurrence of two childhood tumors among relatives. Compared with the general population a second childhood cancer case was 2-3 times more common in a family with a past history of childhood cancer. Verification of diagnosis has been possible for twelve of the nineteen reported relatives. Most common co-occurrence was leukemia-leukemia, lymphoma-hepatoblastoma and neuroblastoma-brain tumor. Except for one proband with Down's syndrome and one with neurofibromatosis 1, none of the families showed a clear family history of cancer that corresponds to a known hereditary cancer syndrome. Screening for p53 germline mutations revealed no mutations. Conclusions: Our results showed that almost every tenth childhood cancer patient had a relative affected with a childhood tumor. Absence of a clear hereditary inheritance may suggest that genes with low penetrance or recessive inheritance are likely to be involved in the development of childhood tumors. In the clinic, pediatricians should be aware of the family history of cancer even in more distant relatives. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1849.