This is a K01 application submitted by Dr. Rafael Guerrero-Preston in response to the funding opportunity announcement """"""""NCI Mentored Research Scientist Development Award to Promote Diversity (K01)"""""""" - PAR-09-052. Rafael, born and raised in Puerto Rico, is currently appointed as an Instructor at the Head and Neck Cancer Research Division of the Department of Otolaryngology at Johns Hopkins School of Medicine. Rafael's short term goals are to examine global, genome-wide and gene-specific epigenomic alterations in tumors that disproportionally burden African American and Latino communities: hepatocellular carcinoma, cervical cancer and head and neck cancers. Dr Guerrero-Preston's long-term goals are: to develop epigenomic biomarkers to improve Head and Neck Cancer (HNSCC) early detection and clinical management;and to contribute to the reduction of survival disparities in oral and oropharyngeal cancer. The proposed K01 project addresses two objectives relevant to the National Cancer Institute mission: to train culturally diverse cancer researchers;and to eliminate cancer health disparities. The overall HNSCC survival rates for African American patients in the United States has remained close to 20% higher than Whites for more than 30 years, but the biological basis for this disparity is poorly understood. A two-stage epigenomic study design is proposed to test the hypothesis that epigenetic alterations contribute to ethnic disparities in HNSCC survival by examining the following aims:
Specific Aim 1 : a) To assess differences of global DNA methylation across ethnic groups in tumor-surgical margins pairs of HNSCC patients (n=500);b) To quantify NID2 and HOXA9 differential methylation across ethnic groups in tumor-surgical margins pairs of HNSCC patients (n=500);c) To evaluate the association between differential methylation in tumor-surgical margin pairs, TP53 mutation status, and clinical outcome, including local recurrence and survival across ethnic groups.
Specific Aim 2 : a) To assess differences of global DNA methylation across ethnic groups in tumor tissue from HNSCC cases (n=300) and normal oral mucosa controls (n=300);b) To quantify NID2 and HOXA9 differential methylation across ethnic groups in tumor tissue from HNSCC cases (n=300) and normal oral mucosa controls (n=300);c) To evaluate the association between differential methylation in tissue and clinical outcome, including local recurrence and survival across ethnic groups. This K01 project strengths are multiple: mentorship by two world leaders in HNSCC genomics, David Sidransky and Wayne Koch;solid institutional support;use of world class research facilities in Johns Hopkins School of Medicine;and access to well characterized sample repositories - the ECOG E4393/RTOG 9614 study, a large multi-institutional head and neck cancer tumor-surgical margin study cohort with abundant outcome data;and a retrospective case-control study from samples stored by the Johns Hopkins Head and Neck Cancer SPORE
The overall Head and Neck Cancer (HNSCC) survival rates for African American patients in the United States has remained close to 20% higher than Whites for more than 30 years, but the biological basis for this disparity is poorly understood. We propose a novel two-stage epigenomic study design to test the overall hypothesis that epigenetic alterations contribute to ethnic disparities in HNSCC survival.
|Pirini, Francesca; Rodriguez-Torres, Sebastian; Ayandibu, Bola Grace et al. (2018) INSIG2 rs7566605 single nucleotide variant and global DNA methylation index levels are associated with weight loss in a personalized weight reduction program. Mol Med Rep 17:1699-1709|
|Pirini, Francesca; Noazin, Sassan; Jahuira-Arias, Martha H et al. (2017) Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies. Oncotarget 8:38501-38516|
|Pirini, Francesca; Goldman, Lynn R; Soudry, Ethan et al. (2017) Prenatal exposure to tobacco smoke leads to increased mitochondrial DNA content in umbilical cord serum associated to reduced gestational age. Int J Environ Health Res 27:52-67|
|Guerrero-Preston, Rafael; White, James Robert; Godoy-Vitorino, Filipa et al. (2017) High-resolution microbiome profiling uncovers Fusobacterium nucleatum, Lactobacillus gasseri/johnsonii, and Lactobacillus vaginalis associated to oral and oropharyngeal cancer in saliva from HPV positive and HPV negative patients treated with surgery and Oncotarget 8:110931-110948|
|Guerrero-Preston, Rafael; Godoy-Vitorino, Filipa; Jedlicka, Anne et al. (2016) 16S rRNA amplicon sequencing identifies microbiota associated with oral cancer, human papilloma virus infection and surgical treatment. Oncotarget 7:51320-51334|
|Pirini, Francesca; Guida, Elisa; Lawson, Fahcina et al. (2015) Nuclear and mitochondrial DNA alterations in newborns with prenatal exposure to cigarette smoke. Int J Environ Res Public Health 12:1135-55|
|Kagohara, Luciane Tsukamoto; Schussel, Juliana L; Subbannayya, Tejaswini et al. (2015) Global and gene-specific DNA methylation pattern discriminates cholecystitis from gallbladder cancer patients in Chile. Future Oncol 11:233-49|
|Guerrero-Preston, Rafael; Hadar, Tal; Ostrow, Kimberly Laskie et al. (2014) Differential promoter methylation of kinesin family member 1a in plasma is associated with breast cancer and DNA repair capacity. Oncol Rep 32:505-12|
|Guerrero-Preston, Rafael; Michailidi, Christina; Marchionni, Luigi et al. (2014) Key tumor suppressor genes inactivated by ""greater promoter"" methylation and somatic mutations in head and neck cancer. Epigenetics 9:1031-46|
|Brebi, Priscilla; Maldonado, Leonel; Noordhuis, Maartje G et al. (2014) Genome-wide methylation profiling reveals Zinc finger protein 516 (ZNF516) and FK-506-binding protein 6 (FKBP6) promoters frequently methylated in cervical neoplasia, associated with HPV status and ethnicity in a Chilean population. Epigenetics 9:308-17|
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