Genetic Associations and Mechanisms in Oncology (GAME-ON): A Network of Consortia for Post-Genome Wide Association (Post-GWA) Research
- Background and Overall Goals
- Funded Projects
- Working Groups and Organizational Structure
- Selected GAME-ON Publications
- Research Tools and Other Research Resources
- NCI Contacts
Background and Overall Goals
The Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative was launched by NCI in 2010 in response to RFA-CA-09-002, and was jointly supported by the Epidemiology and Genomics Research Program and the Division of Cancer Biology. GAME-ON's overall goal was to foster an intra-disciplinary and collaborative approach to the translation of promising research leads deriving from the initial wave of cancer genome-wide association studies (GWAS).
The long-term goal of the GAME-ON initiative was to provide a rigorous knowledge base that would enable clinical translation and public health dissemination of cancer GWAS findings. Teams of epidemiologists, basic scientists, and clinicians accomplished this goal by collaborating on follow-up investigations of genomic regions that have been implicated in susceptibility to certain cancer types. The post-GWAS continuum of research addressed by this network of consortia includes:
- Replication of previous findings and identification of new susceptibility loci through pooled or meta analyses and extension of GWAS to diverse populations,
- Fine mapping of identified loci to better pinpoint causal variants,
- Unraveling the function of identified genetic variants through functional and animal models studies,
- Examining the effect of gene-gene and gene-environment interplay in modulating the risk of disease, and
- Using the knowledge acquired from these studies to develop risk prediction mechanisms that can be used by the general population and in clinics.
Funded Projects, Working Groups, and Organizational Structure
There were five cooperative agreements (U19) funded through the GAME-ON initiative. Each U19 included three projects focusing on the genomic, functional, and epidemiologic follow-up of GWAS of breast, prostate, colon, lung and ovarian cancers. The 5-year funding awards with 2-year no-cost extensions that were granted for this project ended in 2017.
Click the links below each of the following project names to view brief descriptions of each project, links to more detailed abstracts, key personnel lists, and links to study information in the NIH database of Genotypes and Phenotypes (dbGaP). To maximize the scientific benefit and impact of the GAME-ON program, funded investigators were obligated to agree to data sharing requirements as outlined in the general NIH and NCI policies for sharing large data sets.
- ColoRectal Transdisciplinary Study (CORECT)
Learn more about the CORECT studyContact PI: Stephen Gruber, M.D., Ph.D., M.P.H., University of Southern California
The CORECT project investigated and identified susceptibility loci for colorectal cancer in order to characterize the biologic basis of inherited susceptibility and recognize how genetic variation may be quantified and modified by genetic and environmental risk factors. Complex models that take advantage of this new genetic information, together with known environmental factors for colorectal cancer, will expedite the translation of these findings into clinical practice.
- Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE)
Learn more about the DRIVE study
Contact PI: David Hunter, M.B.B.S., Sc.D., Harvard University School of Public Health
The DRIVE project systematically discovered and replicated additional common genetic variants associated with breast cancer, assessed their biological significance, and developed evidence-based assessments of the clinical validity of prediction algorithms using these variants, as well as investigated their suitability for translation into clinical practice.
- Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE)
Learn more about the ELLIPSE study
Contact PI: Christopher Haiman, Sc.D., University of Southern California
The ELLIPSE project pursued thorough identification and characterization of genomic loci associated with prostate cancer. The overarching goal was to discover the pathways that drive prostate cancer pathogenesis and to assess their role in clinical decision making.
- ELLIPSE Prostate Cancer Meta-Analysis and Genotyping
- ELLIPSE Prostate Cancer Genotyping (a sub-study of previous bullet)
- Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)
Learn more about the FOCI study
Contact PI: Thomas Sellers, Ph.D., M.P.H., H. Lee Moffitt Cancer Center & Research Institute
GWAS have successfully identified many common susceptibility alleles for multiple disease phenotypes, including the identification of genes involved in pathways not previously implicated in cancer. This was not previously possible for ovarian cancer, but the recent completion of several independent GWAS, with the potential for replication in participating Ovarian Cancer Association Consortium (OCAC) sites, provided the opportunity to identify such alleles and match the success for other cancers.
- Transdisciplinary Research in Cancer of the Lung (TRICL)
Learn more about the TRICL study
Contact PI: Christopher Amos, Ph.D., Dartmouth College
The TRICL project integrated data from eight GWAS studies on lung cancer to increase power to detect genetic factors influencing all types of lung cancer and to be able to analyze specific subsets, such as cases with early onset, specific histological sets, gender-defined groups, and never smokers. The extended sample size allowed the study of gene-environment interactions. The goal was to identify individuals at high risk for lung cancer for whom screening and early detection would be most beneficial.
Working Groups and Organizational Structure
Each of the five projects contained six GAME-ON Working Groups that promoted scientific collaborations in specific areas across cancer types:
- Analytic and Risk Modeling Working Group
- Epidemiology and Clinical Working Group
- Epigenetics Working Group
- Functional Assays Working Group
- Next Generation Genomics Technologies Working Group
- TERT-CLPTM1L Working Group
An Executive Committee composed of the Lead Investigators of the five U19s established the policies and processes across the initiative. NCI has appointed an External Advisory Committee that provided advice on the overall initiative progress.
Selected GAME-ON Publications
Since the Initiative's inception in 2010, GAME-ON investigators have published more than 400 scientific manuscripts.
Research Tools and Other Research Resources
Investigators also developed analytic software and tools that can be used by the scientific community at large.
For questions related to the GAME-ON grant awards:
For OncoArray questions: