Abstract 1893: Cancer risk in families with childhood adrenocortical tumors, choroid plexus tumors and rhabdomyosarcoma
Authors: Magnusson Susanne , Wiebe Thomas , Kristoffersson Ulf , Olsson Håkan 
Published: July 2012

Abstract
Background: Childhood adrenocortical tumors (ACT), choroid plexus tumors (CPT) and rhabdomyosarcoma (RMS) belong to the core tumors in Li-Fraumeni syndrome. We aimed to study the cancer risk for relatives to children with these diagnoses and if tumor spectra is associated with Li-Fraumeni syndrome (LFS).
Material and Methods: Children (≤18 years) diagnosed with either ACT (n=3) or CPT (n=7) and children (≤ 5 years) diagnosed with RMS (n=29) between 1958-2008 were identified by the population based Cancer Registry of South Sweden. First to third degree relatives were identified by the Swedish Population Registration. Information about vital status and tumor diagnoses, diagnosed between 1958-2008, were collected by linking the unique personal identification number to the Total Populace Register and the Swedish Cancer Registry respectively. Person year at risk were stratified by age, sex and calendar year and multiplied by year-, age-, and sex specific rates of cancer types of interest from Swedish National data to yield expected rates of each type of cancer. Standardized morbidity ratios (SMR), was computed with 95 % confidence interval (CI). A total number of 1376 relatives (44 699 person years) were included in the analyses. Mutational screening for TP53 mutation was performed for probands still alive; ACT n=3, CPT n=5 and RMS n=18.
Results: The risk and tumor spectra among relatives differed between the three histological subtypes. A significant increased risk was seen for relatives to patients with CPT and RMS (SMR=1.84, 95 % CI: 1.34-2.47, p&lt; 0.001; SMR=1.52, 95 % CI: 1.29-1.77, p&lt;0.001, respectively) while a non-significant increased risk was found for relatives to children with ACT (SMR=1.62, 95 % CI: 0.77-2.97, p=0.10). Overall, women seemed to be more affected then men. A significant increased risk for early (&lt;50 years) breast cancer was found for relatives to children with CPT (SMR=3.97, 95 % CI: 0.82-11.61, p=0.04). A significant increased risk for kidney-, pancreas- and lung tumors was found among female relatives to CPT-patients. Among relatives to children with RMS a significantly increased risk for melanoma was found among women both early (&lt;50 years) and before 80 years of age (SMR=6.58, 95% CI: 1.79-16.85, p=0.004 and SMR=2.68, 95 % CI: 0.87-6.25, p=0.04, respectively). Also a significantly increased risk for ovarian-, prostate- and squamous cell cancer of the skin was found among relatives to RMS patients. A non-significant increased risk for sarcoma was also seen for RMS relatives. Mutational TP53 screening revealed a germline mutation only in two out of 26 probands; in a child with ACT and RMS, respectively.
Conclusion: Different patterns of tumors were seen for the histological subtypes of the proband. The observed tumor spectra is not a typical one for LFS which is in line with the TP53 screening results. This suggests that so far unrecognized family associations may account for the main findings.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1893. doi:10.1158/1538-7445.AM2011-1893