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Human Cancer Genetics Programme

Genetic & Molecular Epidemiology Group

Group Leader:  Núria Malats
Research highlights
Research findings

During 2017, the Group centred its research on pancreatic and bladder cancers. Regarding pancreatic cancer (PC), we have completed several analyses using the resources from the PanGenEU Study. In this regard, we reported that specific multimorbidities aggregate and associate with PC risk in a time-dependent manner. A common genetic basis between these conditions and PC was observed through a bioinformatics analysis (FIGURE 1). The common genetic basis between these conditions and PC pointed to a mechanistic link between these diseases. Using the same population and applying both a casecontrol and a reconstructed cohort approach, we confirmed that family history of any cancer, of PC or diabetes, conferred a higher risk of PC and also that smoking notably increased the PC risk associated with family history of PC. Furthermore, we actively participated in an international large-scale investigation that identified important disparities on PC resection practice within and between countries. It also evidenced that most PC patients remain untreated through resection, although resection was associated with better survival, highlighting pivotal potentially modifiable areas in PC clinical practice. Regarding bladder cancer (BC), GMEG assessed the complex interrelationships between asthma and BC in the Spanish Bladder Cancer/EPICURO Study population. This study corroborated the notion that asthma was associated with a reduced risk of cancer, especially among aggressive tumours pointing to the relationship between immune response mechanisms and bladder carcinogenesis. The Group also participated in the discovery and validation of both urine and tumour prognostic marker combination in a large European study of non-muscle invasive BC. Whole transcriptome expression profiling of 476 tumours from the same European-based study enabled the further characterisation of bladder cancer subtypes. GMEG also performed a review of the genetic susceptibility to BC risk and progression based on GWAS. Most of the variants were common and conferred small risk and, therefore, they were not clinically actionable at the individual level.

Methodological contributions

Integrative analytic approaches considering different regulatory levels (i.e., host and tumour) are still scarce. To model this multilevel structure, we proposed to apply our previously described Global-LASSO method and compared it with other approaches to integrate genomic, epigenomic, and transcriptomic data from tumour tissue with blood germline genotypes from 181 individuals with bladder cancer included in the TCGA Consortium (FIGURE 2). Global-LASSO performed better than the other methods. GMEG also developed the ‘DoriTool’ that, to our knowledge, is the most complete bioinformatics tool offering functional ‘in silico’ annotation of variants previously associated with a trait of interest, shedding light on the underlying biology and thereby helping the researchers in the interpretation and discussion of the results.

Translational activities

A critical review of both PC host- and tumour-based markers evidenced the poorly transferred knowledge into the patient management domain. International and multidisciplinary strategies to identify new markers and properly validate the promising ones are urgently needed in order to implement costefficient primary and secondary prevention interventions in PC. During 2017 we organised a Multistakeholder Brainstorming Meeting on European PC research in Brussels under the auspices of the EUPancreas COST Action (BM1204) and the Pancreatic Cancer Europe (EPC) multistakeholder platform. A report pinpointing the gaps and challenges identified by the researchers and stakeholders attending the meeting were distributed, and recommendations were made for future European activity on PC research.