Project description:Prior studies of Bangladeshi migrants in the UK revealed that reproductive function is adaptive, responding to different environments during childhood by adjusting the timing of puberty, reproductive lifespan and overall reproductive function. Here we aimed to understand the basis of this plasticity. Our goals were to establish whether epigenetic mechanisms play a role in the plasticity of this adaptive reproductive phenotype. We hypothesized that women growing up in Bangladesh would have distinct DNA methylation signatures compared to those who moved to the UK at a young age or were born to Bangladeshi parents in the UK. Some of these environmentally induced epigenetic differences would be detected in buccal cell DNA and reflect the divergent gene expression responsible for the altered reproductive function. The women of the study who grew up in Bangladesh were relatively affluent, well-nourished and rarely performed manual work, but a significant confounding factor in their early life was the level of disease load presenting a chronic immune challenge
Project description:Background: Oral squamous cell carcinoma (OSCC) is a major world health problem with over 400,000 new cases diagnosed annually. Despite advances in surgery and chemo-radiotherapy, the 5 year survival has remained roughly constant at approximately 50% for several decades. The disease is characterized by both clinical and genetic heterogeneity, so elucidating the molecular basis of this heterogeneity would have significant clinical implications. It is well recognized that OSCCs from Asia that are associated with betel quid chewing are phenotypically distinct from those from the West that are predominantly caused by smoking/drinking, but the genetic basis of these differences are largely unknown. The aim of this study is to examine the most related genetic factors, carcinogenic related pathways, and molecular processes that might be responsible for the phenotypic heterogeneity of OSCC between UK and Sri Lankan population groups. Methods: We have compared the gene expression profiles of OSCCs and normal oral mucosal tissues from both Sri Lankan and UK individuals using Affymetrix gene expression arrays. Results: The gene expression profiles of UK and Sri Lankan OSCC are similar in many respects to other oral cancer expression profiles reported in the literature and were mainly similar to each other. However, genes involved in tumor invasion, metastasis and recurrence were more obviously associated with UK tumors as opposed to those from Sri Lanka. Interestingly, Ingenuity Pathway Analysis (IPA) revealed a highly activated cell-mediated immune response in both Sri Lankan normal and tumor samples relative to UK cohorts, which may, in part, explain the less aggressive behavior of these betel quid-induced OSCCs. Conclusion: The development of OSCCs in both UK and Sri Lankan populations appears largely mediated by similar biological pathways despite the differences related to race, ethnicity, lifestyle, and/or exposure to environmental carcinogens. However, IPA revealed a highly activated “Cell-mediated Immune Response” in Sri Lankan normal and tumor samples relative to UK cohorts. It seems likely, therefore, that any future attempts to personalize treatment for OSCC patients will need to be different in Western and Asian countries to reflect differences in gene expression and the immune status of the patients.
Project description:Bulk RNA sequencing of sorted A.Cali09-specific CD4+CD45RA- cells from before and seven days after trivalent seasonal influenza vaccination in healthy UK adults of 18-36 years old and over 65 years old.