No abstract

Gastric cancer contributes to a significant health care burden, being the third most common cause of cancer related deaths worldwide. In the US, gastric cancer incidence and mortality in the Hispanic population is more than double compared to Non-Hispanic whites (NHW). However, a majority of the large-scale gastric cancer genome characterization studies that have been carried so far have been largely limited to non-Hispanic (NH) populations, predominantly Non-Hispanic Whites (NHW). This “mono-ethnic” approach is likely to miss driver mutations that are unique or common in Hispanics but rare in NHWs and can lead to future genomic-driven cancer health disparities. Identification of driver mutations is important to understand the molecular basis of tumorigenesis and to develop better preventive and therapeutic strategies in minority groups like Hispanics. Therefore, the purpose of this study was to characterize gastric cancer somatic changes in the understudied Hispanic population. Somatic mutations were identified using whole exome sequencing (WES) of 36 tumor-normal pairs from Hispanic gastric cancer patients. Microsatellite stability tasting was also performed on all the samples and samples were divided into 27 microsatellite stable (MSS) and 9 microsatellite instable (MSI) cases. Interestingly, preliminary analysis of exome sequencing data delineates differences in mutational profile in our study population compared to publish studies in NH. For example, we found that the frequency of TP53, the most commonly mutated gastric cancer driver in NHs, had a significantly lower frequency in our Hispanic sample (33% in MSS tumors and 11% in MSI tumors compared to 50% in MSS and 35% in MSI tumors reported in TCGA dataset). Similar differences were also found in other frequently mutated gastric cancer genes, which suggest that the genetic pathways leading to gastric cancer in Hispanics are likely to be different to the ones involved in NHW tumors. In summary, our sequencing study of Hispanic gastric cancer cases have identified important differences with other populations, are likely to identify novel cancer drivers in this tumor type and would help bridge the gap in heath care disparities Citation Format: Rodrigo Prieto-Sanchez, Ruta Madhusudan Sahasrabudhe, Paul Lott, Mabel Bohorquez, Jhon Jairo Suarez, Gilbert Mateus, Javier Torres, Magdalena Echeverry, Luis Carvajal-Carmona. Somatic mutation profile of gastric cancer cases from the Hispanic population. [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 4620. doi:10.1158/1538-7445.AM2015-4620

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