Based on epidemiological associations and experimentation, relationships between viruses and cancer have been established. For more than 14 million new cases of cancer per year, it is estimated that 15% are related to viral agents. Epithelial, hematolymphoid and mesenchymal malignancies related to different viruses have been document such as Epstein Barr, Kaposi’s sarcoma, hepatitis B and C, human lymphotropic type 1, Merkel’s carcinoma and human papilloma. New virus with oncogenic potential such as cytomegalovirus, JC polyoma virus and BK have been described. The interaction of the viruses with the host induces oncogene activation, inhibition of tumor suppressor genes and activation of miRNAs, as determining factors in the development of cancer. The pathology is initiated with the infection that induces the deregulation of cell signaling. The Epstein Barr virus is the oncogenic prototype, with 1% of the human cancers related to it.

Gastric cancer (GC) is a leading cause of cancer mortality and health disparities in Latinos. We evaluated gastric intratumoral heterogeneity using multi-regional sequencing of >700 cancer genes in 115 tumor biopsies from 32 patients, 29 who were Latinos. Analyses focused on comparisons with TCGA and on mutation clonality, druggability and signatures. We found that only ~30% of all mutations were clonal and that only 61% of the known TCGA GC drivers harbored clonal mutations. Multiple clonal mutations were found in new candidate GC drivers such as EYS, FAT4, PCDHA1, RAD50, EXO1, RECQL4, and FSIP2. The genomically stable (GS) molecular subtype, which has the worse prognosis, was identified in 48% of our Latino patients, a fraction that was >2.3-fold higher than in TCGA Asian and White patients. Only a third of all tumors harbored clonal pathogenic mutations in druggable genes, with most (93%) GS tumors lacking actionable clonal mutations. Mutation signature analyses revealed that, in microsatellite-stable (MSS) tumors, DNA repair mutations were common for both tumor initiation and progression, while tobacco, POLE, and inflammation signatures likely initiate carcinogenesis. MSS tumor progression was likely driven by aging- and aflatoxin-associated mutations, as these latter changes were usually non-clonal. In microsatellite-unstable tumors (MSI), non-clonal tobacco-associated mutations were common. Our study, therefore, contributed to advancing GC molecular diagnostics and suggests clonal status is important to understanding gastric tumorigenesis. Our findings of a higher frequency of a poor prognosis associated molecular subtype in Latinos and a possible new aflatoxin GC etiology also advance cancer disparities research.

TC is one of the most common malignancy that shows familial inheritance with ∼8 fold increase in the risk of developing TC in first-degree relatives affected by this disease. Recent genome-wide association studies (GWAS) aimed at characterizing the risk loci for TC have identified five single nucleotide polymorphisms (rs966423, rs2439302, rs965513, rs116909374 and rs944289) associated with increased risk for TC. However, effect of these polymorphisms have bot been studied in any Hispanic population. Therefore, the aim of this study was to analyze the above-mentioned SNPs in 235 TC patients and 588 healthy controls from Central Colombia using KASP genotyping system. Genotype frequencies, Hardy Weinberg equilibrium (HWE) and association testing was carried out using Plink. The cumulative genetic risk was assessed using unweighted and weighted approaches. Significant associations between thyroid cancer risk and rs965513A (OR = 1.503, 95% CI: 1.203-1.886, P = 0.00038) and rs944289T (OR = 1.372, 95% CI: 1.095-1.699, P = 0.00488) was observed in our study. Consistent, yet not -significant associations were observed between disease risk and rs2439302T (OR = 1.177, 95% CI: 0.931-1.477, P = 0.1666) and rs116909374A (OR = 1.626, 95% CI: 0.799-3.766, P = 0.2443). For rs966423G, significant departure from HWE was observed therefore this SNP was excluded from further analysis. The combined analyses of rs2439302, rs965513, rs116909374 and rs944289 showed consistent associations between the number of disease alleles and cancer risk. Having three risk alleles increased disease risk by two-fold (OR = 2.09, 95% CI:1.46 - 3.02),while carrying five risk alleles was associated with nearly 4-fold increase in the disease risk (OR = 3.84, 95% CI:1.47 - 10.06). To our knowledge, this was the first study that assessed TC risk associated with known polymorphisms in the Hispanic population and suggest that these variants could be used in future risk prediction profiling studies in these populations. Citation Format: Ana Estrada-Flórez, Mabel E. Bohórquez-Lozano, Rodrigo Prieto-Sánchez, Gilbert F. Mateus, Alejandro Rios, Alejandro Vélez Hoyos, Carlos S. Duque, Mirko A. Ledda, Maria J. Erazo, Fernando Bolaños, Cesar Panqueba, María Magdalena Echeverry de Polanco, Luis G. Carvajal-Carmona. Evaluation of known low-penetrance thyroid cancer risk alleles in a Hispanic population from South America. [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 LB-046. doi:10.1158/1538-7445.AM2015-LB-046

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