Abstract 2753: The germline TP53 p.R337H mutation: a putative selective advantage

Abstract

Abstract Li-Fraumeni syndrome is a hereditary cancer predisposition disorder related to germline TP53 mutations. Although it is considered to be a rare condition worldwide, a high occurrence of a founder mutation, the p.R337H TP53, is present in 0.3% of Southern Brazilian population. In a subgroup of p.R337H carriers, specific characteristics associated with late aging were clinically observed, such as a lower frequency of metabolic alterations and diseases typical of aging. However, despite of these particular features no study has clinically characterized these individuals until the moment. Therefore, our aim was to evaluate clinical features of p.R337H carriers and compare them with a control group. We used a clinical form composed by information on physical characteristics, personal habits, clinical history of diseases and physical activity throughout life. After IRB approval, we applied it in 48 p.R337H carriers (mean age: 46,8; range: 16-100) and in 38 carrier's relatives who were mutation-negative, as controls, (mean age 52,7; range: 18-90). Fisher's exact test was performed for statistical analysis. Regarding personal characteristics and habits, no difference was found between groups neither among p.R337H asymptomatic and affected carriers. However, some diseases discrepancies were found: In individuals older than 55 years of age, prevalence of osteoporosis was significantly lower in the p.R337H group when compared to controls (12% vs 59%; p<0,05). Anemia was also less frequent in p.R337H carriers (0% vs 13%; p<0,05) when all ages are considered. Although non-statistically significant, lower frequencies of neurodegenerative disorders, gastritis and thyroid dysfunction were also observed in the p.R337H group. These findings provide further information about a better overall health in p.R337H carriers, suggesting a possible selective advantage. This could be a plausible explanation for why this deleterious mutation has persisted throughout successive generations. More detailed clinical characterization studies are under way as well as molecular approaches looking for interactions between the p.R337H mutation and cellular senescence mechanisms. Citation Format: Kelvin César Andrade, Ana Carolina Leite, Amanda Nobrega, Sharon Savage, Maria Isabel Achatz. The germline TP53 p.R337H mutation: a putative selective advantage. [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 2753. doi:10.1158/1538-7445.AM2015-2753