Section of Genetics - Genetic Epidemiology Group
Current Research Topics:
Genetic and molecular epidemiology of alcohol- and tobacco-related cancersGEP is currently undertaking large multi-partner genetic epidemiology studies of cancers strongly related to tobacco and alcohol - principally lung and aerodigestive cancers, but also kidney and pancreatic cancers. These include candidate gene studies, and increasingly genomewide association studies.
A series of large multicentre case-control studies of lung, upper aerodigestive and kidney cancer have been completed in Europe and Latin America, comprising over 15 000 subjects. Genomewide association studies are currently underway in collaboration with the Centre National de Genotypage to help identify new genes for these cancers and the first results for lung cancer have been published (Hung et al, Nature 2008; Mc Kay et al, Nature Genetics, 2008). The Group is also working with the International Lung Cancer Consortium (ILCCO) and the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, with the aim of pooling information and results from all large studies of lung and aero-digestive cancers.
A large genome-wide study of kidney cancer is also underway, in collaboration with the Centre National de Genotypage (Evry, France) and the US National Cancer Institute.
Genetic susceptibility of renal cancersBased on a series of studies including a large case-control study from central Europe coordinated by GEP scientists (1400 cases and 2500 controls), the EPIC cohort study (300 cases and 400 controls) and an additional 3 studies, the final dataset comprised approximately 2500 cases and 5000 controls. This data was combined with a parallel study coordinated by scientists at the US NCI (principally Stephen Chanock and Nat Rothman) comprising approximately 1300 cases and 3400 controls. A combined dataset of approximately 3800 cases and 7400 controls using standardised quality control thresholds and common variable definitions was developed, with coordinated analysis at both IARC and the NCI. This study has resulted in the identification of 3 novel susceptibility loci for renal cell cancer. (Purdue et al, Nature Genetics, in press).
Genetic investigations into pancreatic cancer are expected to start soon. As part of this initiative, we are coordinating a large case-control study of pancreatic cancer in Slovakia and Czech Republic, and are participating in the Pancreatic Cancer Case-Control Consortium (PANC4)
International study of rare childhood embryonal tumours (ISET)Following a meeting held in IARC in 2006 that comprised investigators with an interest in childhood cancers, a large scale etiological study of rare childhood cancers was piloted in eight countries in 2008-2010 (France, UK, Canada, Australia, Canada, USA, Serbia, Macedonia, Czech Republic). A case-control trio design has been shown to be feasible in all countries participating to the pilot, and four additional countries (Brazil, Japan, India, the Netherlands) may start piloting the protocol in 2011. The aim of this study is to investigate the role of exposure to suspected factors at different key periods (preconceptional, prenatal, and postnatal), as well as genetic susceptibility factors, gene-environment interactions, and novel molecular markers. Focusing on Wilms tumour and neuroblastoma, already more than 250 case trios and 1750 unrelated controls have been recruited, with approximately 650 and 450 case trios expected each year, respectively. The full scale study will expand to retinoblastoma, rhabdomyosarcoma, and hepatoblastoma.
Renal cell cancer (RCC) genetics and genomics (Cagekid)As part of our central role in the CAGEKID study, we will undertake a comprehensive evaluation of the germline and somatic variation that contributes to risk of the RCC and subsequent outcome. This will be complemented by an examination of the role of gene expression and epigenetic changes. Short term goals for GEP will be to ensure the availability of at least 100 cases that correspond to the ICGC criteria for full participation in the CAGEKID study comprising whole genome sequencing and expression analysis of tumour/non-tumour pairs. Subsequently, we will bring together a comprehensive biorepository of at least 2000 cases with complete genomic material (eg tumour/non-tumour DNA and RNA, blood DNA), baseline information, treatment details and follow-up information. This biorepository will be used to conduct focused sequencing and expression analysis based on the initial series of 100 cases (as part of a large consortium led by the CNG (PI: Mark Lathrop)). While our main responsibility rests with recruitment of all subjects and creation of the biorepository, GEN scientists are also well placed to conduct comprehensive analyses that incorporates genetic, epidemiology and clinical data. For GEN to participate fully in the analysis and interpretation of these data, this project will necessarily require an increased capacity within the Section in both next generation sequencing and bio-informatics analysis.
Concurrent with the RCC genomics project, we will expand our genome-wide study of RCC by doubling the sample size (to 8000 cases and many more controls) and utilizing denser genotyping chips. We will also obtain outcome information on at least 3000 cases, allowing for a GWA study of disease outcome. Whole genome sequence information on a subset of cases will greatly enhance imputation of rarer variants. This GWA project will be conducted in close collaboration with colleagues at the US NCI.