Hundreds of researchers have joined together in a large-scale cancer genotyping project focused on lung, breast, ovarian, prostate, and colorectal cancers. The OncoArray Consortium plans to perform germline genotyping of 425,000 blood samples pooled from consortium members by July 2014, using a custom genotyping chip that includes 530,000 single nucleotide polymorphisms.

Hundreds of researchers from nearly 50 countries have joined together in a large-scale cancer genotyping project focused on lung, breast, ovarian, prostate, and colorectal cancers.

The OncoArray Consortium plans to perform germline genotyping of 425,000 blood samples pooled from consortium members by July 2014.

To support the project, the Consortium collaborated to create a custom OncoArray genotyping chip that includes 530,000 single nucleotide polymorphisms (SNP). Project researchers also can add up to 120,000 more custom SNPs.

“There have been other examples of collaboratively designed custom chips used across a wide variety of studies with the intent of pooling the data, but I think this is the biggest one so far—certainly the biggest in cancer—in terms of number of variants and number of samples,” says David Hunter, ScD, dean for academic affairs at the Harvard School of Public Health in Boston, MA. Hunter is leading the breast cancer genotyping project funded by the National Cancer Institute (NCI).

NCI is providing approximately half of the funding for the project under its Genetic Associations and Mechanisms of Oncology (GAME-ON) initiative. Other funding sources include Genome Canada, Genome Quebec, and Cancer Research UK.

“The big plus is that we'll all be genotyping our samples jointly on the same platform, which will let us compare the findings across the different cancer types and share our controls more effectively,” says Christopher Amos, PhD, leader of the lung cancer project and director of the Center for Genomic Medicine at the Geisel School of Medicine at Dartmouth College in Lebanon, NH.

The project aims to create more precise maps of genomic regions already linked to cancer in genome-wide association studies, identify new cancer-related variants, and find genetic markers of aggressive disease, particularly for prostate and breast cancers.

Consortium researchers have put together plans for more than 200 studies of the data.

Because of the large sample size and common microarray platform, the researchers will also do gene–gene interaction studies to determine if combinations of variants influence risk, says Amos.

For instance, researchers participating from the Consortium of Investigators of Modifiers of BRCA1/2, who are genotyping 30,000 BRCA1/2 mutation carriers, hope to determine if additional variants contribute to the risk for carriers.

“We are finding variants that are plausibly associated with cancer, but the only way to validate them is through these very large massive studies,” says Hunter. “If we can understand why these variants are associated with a certain type of cancer, then we'll learn about biologic causation, which could have a huge payoff in terms of understanding the mechanism and potentially prevention.”

The OncoArray lab system, manufactured by Illumina of San Diego, CA, provides coverage of variants identified in genome-wide association studies for the five cancer sites as well as pharmacogenetic markers and other markers of traits that contribute to cancer risk, such as body-mass index.

Samples are already flowing to the genotyping centers involved. About half of the samples will be genotyped at the Center for Inherited Disease Research at Johns Hopkins University in Baltimore, MD. The data generated will be made public through the National Center for Biotechnology Information's database of Genotypes and Phenotypes. Other centers testing samples include Genome Quebec and the University of Cambridge in the UK.

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