Largest Collaboration of Genetic Research of Cancer Coming to Fruition

Hundreds of scientists worldwide have recently reported the discovery of more than 80 new regions of the human genome that indicate risk for ovarian, breast, and prostate cancer.

The landmark achievement was announced on March 27, 2013, through the coordinated release of 13 papers in five different journals—Nature Genetics, Nature Communications, the American Journal of Human Genetics, PLoS Genetics, and Human Molecular Genetics. The articles described the findings of the Collaborative Oncological Gene-environment Study (COGS), a large international effort that involves investigators from North America, Europe, Australia and Asia, and more than 150,000 worldwide men and women who participated in the study.

“This is far and away the largest genetic study of cancer ever to be reported,” said Prof. Brian Henderson of the department of preventive medicine at the Keck School of Medicine of University of Southern California (USC; USA), who contributed to the identifying new risk areas for breast and prostate cancer. “This study demonstrates the power of international team science that will ultimately provide major health benefits on a global scale.”

Large-scale genome-wide association studies (GWAS) served as the basis for the research. The scientists were searching for genetic variations known as single-nucleotide polymorphisms (SNPs), which signal an increased risk for cancer. They discovered 49 new SNPs linked with risk of breast cancer, 23 for prostate cancer, and 11 for ovarian cancer. One of the most fascinating discoveries is that diverse SNPs predict the risk of different types of breast or ovarian cancer.

“Our study found several SNPs that increase the chance of women developing more aggressive estrogen negative breast cancer rather than estrogen-positive breast cancer,” said Prof. Christopher Haiman, whose research contributed to findings on breast and prostate cancer. “This tells us that these two different types of breast cancer have different underlying biology, and this could affect how we treat the disease.”

Assist. Prof. Celeste Pearce discovered similar findings for ovarian cancer. “The biggest surprise was finding SNPs affecting the risk of two subtypes of ovarian cancer but with different variants affecting each subtype,” she said. “The research has fundamentally changed our understanding of this disease and provided the basis for exploring new pathways in the causes of ovarian cancer.”

More than 2.5 million people worldwide are diagnosed every year with one of the three hormone-related cancers examined in this collaborative research. The finding of genetic features more common in individuals affected with these cancers, compared to healthy subjects, could have a significant impact on cancer mortality. “Ovarian cancer patients usually have a very poor chance of surviving their disease,” said Assoc. Prof. Susan Ramus, who led one of the ovarian cancer studies. “By using genetic information to identify the women at greatest risk of ovarian cancer, and with improved screening, we could detect the disease at its earliest most treatable stages, when it’s curable.”

Genetic risk variants eventually affect one or several genes that affect the biology of healthy cells, leading to cancer, and several of these studies reported new gene targets that may represent the root cause of ovarian, breast, and prostate cancers. “Together, these studies indicate a multitude of previously unknown molecular targets that may cause cancer,” concluded Prof. Simon Gayther, who identified several novel genes reported in the papers. “This represents an unprecedented discovery of clinical biomarkers and therapeutic targets for breast, ovarian, and prostate cancers, which have the potential to save countless lives.”

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Keck School of Medicine of University of Southern California