oa Italian study on gene-environment interactions in lymphoma etiology: Translational aspects

Introduction: The objective of the "Italian Study on gene-environment interactions in lymphoma etiology", hereafter named the Italian GxE Study, is to identify individual conditions and external factors associated with lymphoma aetiology, the response to therapy and survival, as possible targets for preventive action and possible drivers of new individualized therapeutic strategies. Methods: This objective is being pursued by recruiting up to 1000 incident lymphoma cases and 1000 controls in six Italian areas: central and southern Sardinia, Florence, Bari and Taranto, Verona, Novara and Perugia. After signing the informed consent form, cases and controls will donate a blood sample and respond to a detailed questionnaire on health history, lifestyle factors, and occupational and environmental exposures of interest. The interaction between genetic polymorphisms, epigenetic conditions, and the most prevalent lifestyle and occupational exposures will be explored using the case-control epidemiological study design. Survival analysis will be conducted in relation to the therapeutic protocol, lifestyle variables, and gene polymorphisms using a modified proportional hazard model. Study design: Here are the main features of the Italian GxE study: 1. Genome Wide Scan of patients and controls DNA, which aims to evaluate several million SNPs, some functionally known, and other in strict linkage disequilibrium with genes in loci encoding for known proteins, using last generation high throughput platforms (Illumina (R) Human660W). 2. Use of the Telepathology Network to reach maximum consensus among the pathologists' panel collaborating in this project so achieving the maximum diagnostic precision, by applying the most recent lymphoma classification schemes consistently across the study areas. 3. Detailed assessment of occupational and environmental exposure, thanks to the experts in retrospective exposure assessment participating in our project and the continuous refinement of the questionnaires which have been used in international studies for the last two decades. Precision in defining external exposures is of paramount importance to effectively explore gene-environment interactions in the aetiology of the different lymphoma subtypes. 4. Analysis of response to therapy and survival of lymphoma patients in relation to their genetic features, which will allow to design future individualized therapeutic schemes, by identifying responders to specific chemotherapeutic agents based upon their polymorphisms of genes implicated in xenobiotic metabolism, DNA repair, release of inflammatory cytokines, as well as other yet to be identified. Conclusion: The Italian GxE Study contributes to the International InterLymph Consortium (http://epi.grants.cancer.gov/InterLymph/), which creates the necessary synergy to inquire into lymphoma etiology in general, and its individual subtypes in particular.