Evaluation of social deprivation as a modifier of phenotypic divergence in PTEN Hamartoma Tumor Syndrome
Parker L. Bussies,
David Bruckman,
Lamis Yehia,
Takae Mizukami,
Karen Hurley,
Jarrod Dalton,
Charis Eng
Affiliations
Parker L. Bussies
Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Obstetrics and Gynecology Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Personalized Genetic Healthcare, Medical Specialties Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Correspondence to: 9500 Euclid Avenue, Cleveland, OH 44195, USA.
David Bruckman
Center for Populations Health Research, Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH 44195, USA
Lamis Yehia
Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
Takae Mizukami
Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Personalized Genetic Healthcare, Medical Specialties Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA
Karen Hurley
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA; Center for Adult Behavioral Health, Cleveland Clinic, Cleveland, OH 44195, USA
Jarrod Dalton
Center for Populations Health Research, Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH 44195, USA
Charis Eng
Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Personalized Genetic Healthcare, Medical Specialties Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; Germline High Risk Focus Group, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
Pathogenic mutations in phosphatase and tensin homolog (PTEN), a tumor suppressor gene, leads to the development of PTEN Hamartoma Tumor Syndrome (PHTS). Patients carry significantly increased risks for cancer and neurodevelopmental disorders such as autism spectrum disorder (ASD). The factors which modify PTEN function and drive PHTS phenotype remain unknown. Social determinants of health are increasingly being identified as important regulators of disease pathogenesis. Here, we conduct a retrospective cross-sectional study to evaluate the association between social deprivation, as measured by area deprivation index (ADI), and neurodevelopmental versus cancer phenotypes in patients with PHTS. Our findings suggest ADI alone is not associated with PHTS phenotype, and that its divergence is likely multifactorial in nature. More broadly, our study highlights the importance of integrating environmental pressures with genetic risk modification in the study of complex human disease.
