M3 - NCI Cancer Genetic Markers of Susceptibility (CGEMS) Initiative: Replication Phase

This page provides study documentation for consortium study M3.  For description of the specimen results, see Specimen Results Description (open to public). Data sets of the specimen results are included in the existing WHI datasets located on the WHI Data on this site (sign in and a completed Data Distribution Agreement are required; see details on the Data site).

Investigator Names and Contact Information

Stephen Chanock, MD, NCI


To help meet the Challenge Goal of eliminating suffering and death from cancer by 2015, the NCI is capitalizing on the extraordinary momentum generated by advances in human genetic research.  The sequencing of the human genome and the annotation of common variations, together with new technologies for analyzing SNPs, have provided the tools for investigators to actively search for inherited variants in genes that increase or decrease cancer risk.  The convergence of sequencing the human genome, rapid progress in the International HapMap project, and the development of technologies that permit very large-scale SNP genotyping has made it possible to execute well-designed association studies using common variants across the entire genome to map low-penetrant genes involved in cancer susceptibility.  The results of such studies are expected to open new vistas in the search for causal pathways in cancer induction and progression that will lead to targets for novel intervention strategies. 

The Cancer Genetic Markers of Susceptibility (CGEMS) initiative (Cancer Bulletin, 2005, Vol 2, Number 16, page 7) will use the latest genomic technologies to perform dense whole genome scans to identify and validate susceptibility genes in the induction and progression of prostate and breast cancer (pancreatic cancer will not be studied under this Collaboration Agreement).  CGEMS represents a three year NCI enterprise initiative that will be coordinated through the Division of Cancer Epidemiology and Genetics (DCEG), the NCI Core Genotyping Facility (CGF) and the NCI Office of Cancer Genomics (OCG). CGEMS is a resource for the strategic partnerships between intramural and extramural groups that are joining forces to incorporate genomic and other emerging technologies in large-scale epidemiologic studies. CGEMS promises to provide new insights into the genetics of carcinogenesis, and point the way to novel strategies for meeting the 2015 Challenge Goal by accelerating the prevention, early detection, and treatment of cancer.
A major goal of CGEMS is to make study findings publicly accessible within four months after completion of genotyping through the NCI’s Cancer Biomedical Informatics Grid (caBIG). This access will ensure rapid sharing of results in order to stimulate further analytical and methodological use of the dataset by the extramural scientific community and point to genomic regions which can be followed up by all investigators.
The initial whole genome scan of 550K SNPs for breast cancer will be conducted using specimens from other cohorts.  The Women’s Health Initiative (WHI) Observation Study specimens will be used in the first replication/follow-up stage, that will involve approximately 30K SNPs selected on the basis of the initial whole genome scan. The first replication stage will include approximately 2952  cases of pathologically confirmed breast  cancer among Caucasian women and approximately 2952  controls matched for age, ethnicity (Caucasians of European descent), date of WHI enrollment, prevalent disease status at enrollment, and hysterectomy status.  
The samples obtained from WHI wiill be genotyped by the NCI with about 30,000 SNPs (based on position in the coordinated follow-up studies) that are expected to emerge from the analysis of the initial whole genome scan described above. These SNPs will be analyzed in the NCI’s Core Genotyping Facility using commercially available, high-throughput genotyping technology from Illumina, Inc.
After the initial analysis, the most significant genomic regions of interest will advance to the next refinement stage. Additional SNPs may be added to further define regions of interest. These additional SNPs will be genotyped on the same FHCRC data set to refine the position of loci that confer susceptibility to breast cancer.
Selection Criteria
·          2,956 invasive breast cancer cases as of Sept. 2005, confirmed by SEER coding
·          Observation Study participant
·          Consented for genetic studies
·          Caucasian
  Controls matched by
·          Age
·          Ethnicity (Caucasians of European descent),
·          Date of WHI enrollment,
·          Prevalent disease status at enrollment, and
·          Hysterectomy status.  


See publications: 874, 906, 907, 1104. WHI publications by study lists published WHI papers that have been generated by ancillary studies. A complete list of WHI papers is available in the Bibliography section of this website.