The study is one of 13 papers to be published simultaneously in five journals by the Collaborative Oncological Gene-environment Study (COGS), an international research collaboration involving investigators from Europe, Asia, Australia and North America, including Mayo Clinic. This landmark series of papers provides genotyping results from more than 250,000 individuals that look at DNA sequences involved in three hormone-related cancers: ovarian, breast and prostate.
"Through the combined efforts of this consortium, and all the data sharing, we are much closer to understanding the inherited factors in these diseases," says Mayo Clinic investigator Ellen Goode, Ph.D., senior author of the HNF1B paper, and co-author of three additional papers among the 13, focusing on ovarian and breast cancer development. Ovarian cancer is the most common cause of death from gynecological cancers in the U.S.
In their study, Dr. Goode and her collaborators showed that variations in the HNF1B gene are overrepresented in one type of epithelial ovarian cancer and underrepresented in another type. They also found that variation in DNA methylation, a process that moderates the expression of genes such as HNF1B, correlates with different ovarian cancer subtypes. This finding suggests that the activation and inhibition of gene expression by DNA methylation can be as important a factor in cancer as genetic mutations.
"The distinct methylation patterns suggest a molecular mechanism by which changes in this gene lead to increased cancer risk," says Dr. Goode. "This has potential clinical implications for improving our understanding of how the disease begins, for better identification of ovarian cancer subtypes and for developing novel treatment approaches."
Celeste Leigh Pearce, Ph.D., of the Keck School of Medicine, University of Southern California, Los Angeles, is co-senior author of the study. Other co-authors of COGS papers include Fergus Couch, Ph.D.; Julie Cunningham, Ph.D.; Kimberly Kalli, Ph.D.; Janet Olson, Ph.D.; Susan Slager, Ph.D.; Stephen Thibodeau, Ph.D.; and Celine Vachon, Ph.D.; all of Mayo Clinic.
Funding for the study came from the Ovarian Cancer Research Fund, the Genetic Associations and Mechanisms in Oncology (GAME-ON) Network (U19 CA148112), the European Union Seventh Framework, Cancer Research UK, the Mayo Clinic Ovarian Cancer SPORE (P50 CA136393), and the National Cancer Institute (R01 CA122443), the Fred C. and Katherine B. Andersen Foundation, and the Minnesota Ovarian Cancer Alliance.
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