RESUMO
BACKGROUND: Hispanic/Latino populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. The molecular profile of breast cancer has been widely described in non-Hispanic Whites but equivalent knowledge is lacking in Hispanic/Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian women was Luminal B as defined by St. Gallen 2013 criteria. In this study we explored ancestry-associated differences in molecular profiles of Luminal B tumors among these highly admixed women. METHODS: We performed whole-transcriptome RNA-seq analysis in 42 Luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to Luminal subtype and to the proportion of European and Indigenous American ancestry and performed differential expression analysis comparing Luminal B against Luminal A tumors according to the assigned ancestry groups. RESULTS: We found 5 genes potentially modulated by genetic ancestry: ERBB2 (log2FC = 2.367, padj<0.01), GRB7 (log2FC = 2.327, padj<0.01), GSDMB (log2FC = 1.723, padj<0.01, MIEN1 (log2FC = 2.195, padj<0.01 and ONECUT2 (log2FC = 2.204, padj<0.01). In the replication set we found a statistical significant association between ERBB2 expression with Indigenous American ancestry (p = 0.02, B = 3.11). This association was not biased by the distribution of HER2+ tumors among the groups analyzed. CONCLUSIONS: Our results suggest that genetic ancestry in Hispanic/Latina women might modify ERBB2 gene expression in Luminal tumors. Further analyses are needed to confirm these findings and explore their prognostic value.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Colômbia , Feminino , HumanosRESUMO
Infection with Helicobacter pylori has been recognized as a cause of gastric carcinoma. Although the neoplasia is always detected in adults, the infection starts in childhood. It has been reported that early age at first infection is a determinant of gastric cancer risk. In this study, we examined the histopathology of the gastric mucosa in infected children from a population at high risk for gastric cancer (Pasto, Colombia) and compared it with that of a lower-risk population (New Orleans, LA). Gastric biopsies obtained from antrum and corpus were stained with hematoxylin and eosin and Steiner's silver method. Immunohistochemical stains were used to identify B lymphocytes (CD20), T lymphocytes (CD3 and CD8), macrophages (CD68), and polymorphonuclear neutrophil myeloperoxidase. Morphometric techniques were used to evaluate the immunohistochemical stains. In both populations, the inflammatory lesions were seen predominantly in the antrum. Compared with children from the lower-risk populations, children from the higher-risk population exhibited more severe polymorphonuclear neutrophil infiltration, stromal and intraepithelial lymphocyte infiltration, mucus depletion, and H. pylori colonization density. Regenerative activity was significantly more marked in the lower-risk population. Morphometric analysis of immunohistochemical stains showed increased representation of T lymphocytes and macrophages in the higher-risk population. Most T lymphocytes stained positive for CD8, a marker of suppressor/cytotoxic cells. B lymphocytes were relatively more abundant in the lower-risk population. The possibility that the aforementioned characteristics of H. pylori infection in children are related to cancer risk in adults is discussed.