USC scientists contribute to international research on genetic risks for cancer
Researchers from the USC Norris Comprehensive Cancer Center are joining hundreds of scientists worldwide in reporting the discovery of more than 80 new regions of the human genome that indicate risk for breast, ovarian and prostate cancer.
The milestone was announced on March 27 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 papers 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 Distinguished Professor Brian Henderson of the Department of Preventive Medicine at the Keck School of Medicine of USC, who contributed to the finding of new risk regions 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 looking for genetic variations known as single-nucleotide polymorphisms, or SNPs, that indicate an increased risk for cancer. They found 49 new SNPs associated with risk of breast cancer, 23 for prostate cancer and 11 for ovarian cancer. One of the most intriguing findings is that different 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 Professor 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.”
Assistant Professor Celeste Pearce discovered something similar 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,” Pearce 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 throughout the world are diagnosed every year with one of the three hormone-related cancers studied in these papers. 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 Associate Professor 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 ultimately affect one or several genes that affect the biology of normal cells, leading to cancer, and several of these papers reported novel gene targets that may represent the root cause of breast, ovarian and prostate cancers.
“Together, these studies indicate a multitude of previously unknown molecular targets that may cause cancer,” said Professor 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.”
USC researchers represented the Department of Preventive Medicine and the USC Epigenome Center and served as co-authors on all 13 papers. In addition to Henderson, Haiman, Pearce, Ramus and Gayther, contributing co-authors from USC were Doerthe Brueggmann, Gary Chen, Gerhard Coetzee, Roman Corral, Ye Feng, Sue Ingles, Rod Karevan, Peter Laird, Kate Lawrenson, Alice Lee, Malcolm Pike, Suhn Kyong Rhie, Fredrick Schumacher, Ahva Shahabi, Howard Shen, Hui Shen, Mariana Stern, Daniel Stram, Douglas Stram, Claire Templeman, Chiu-Chen Tseng, David Van Den Berg and Anna Wu.
Funding for the research came from Cancer Research UK, the National Institutes of Health, the Congressionally Directed Medical Research Program, the Ovarian Cancer Research Fund, COGS (from European Union Seventh Framework), the National Institutes of Health’s Genetic Association Mechanisms in Oncology consortium and others.
Consortia involved in the research included the Ovarian Cancer Association Consortium, the Breast Cancer Association Consortium, the Prostate Cancer Association to Investigate Cancer Associated Alterations in the genome and the Consortium of Investigation of Modifiers of BRCA 1 and 2.