Cancer researchers say a large genome-wide association study (GWAS) that spanned three continents has identified four chromosome locations with genetic changes that are likely to alter a woman's risk of developing ovarian cancer. 

Researchers say that while more needs to be learned about the function of the specific chromosomal regions involved in susceptibility, the discoveries move them a major step closer to individualized risk assessments for ovarian cancer. In the future, women at greatest risk due to these and other inherited changes may be offered increased surveillance or preventive measures.

"In searching the genome, we came up with some surprises on chromosomes 2, 3, and 17," says Ellen Goode, Ph.D., Mayo Clinic genetic epidemiologist and lead author of the study. "While examining the usual suspects in a region on chromosome 8, we found that SNPs associated with ovarian cancer risk were located quite a distance away from those associated with risk of other cancers, which suggest that they may act through a different mechanism."

SNPs, single nucleotide polymorphisms, are common genetic variants associated, in this case, with cancer risk.

After the genome-wide association study of over 1,700 cases, the researchers followed up with a study of over 24,000 women. They narrowed the focus to nine regions and confirmed that three loci (locations on the chromosome) were much stronger than the others and a fourth "approached genome-wide significance."

These particular loci are associated with serous ovarian cancer, the most aggressive and common of the four main types of the disease.

The Ovarian Cancer Association Consortium authors identified an additional locus on chromosome 19 in a second study, also published in the same issue of Nature Genetics (Kelly L Bolton, Jonathan Tyrer, Honglin Song, Susan J Ramus, Maria Notaridou, Chris Jones, Tanya Sher, Aleksandra Gentry-Maharaj, Eva Wozniak, Ya-Yu Tsai, et al, 'Common variants at 19p13 are associated with susceptibility to ovarian cancer', Nature Genetics (19 September 2010) doi:10.1038/ng.666).   

Yet another paper in the same issue, co-authored by Mayo researcher Fergus Couch, Ph.D., found SNPs moderating breast cancer in the BRCA1 gene (Antonis C Antoniou, Xianshu Wang, Zachary S Fredericksen, Lesley McGuffog, Robert Tarrell, Olga M Sinilnikova, Sue Healey, Jonathan Morrison, Christiana Kartsonaki, Timothy Lesnick, et al., 'A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor–negative breast cancer in the general population', Nature Genetics (19 September 2010) doi:10.1038/ng.669 ). Many of the genes in question carry mutations impacting both ovarian and breast cancer, increasing the risk for some women. 

In addition to Dr. Goode, and corresponding author Simon Gayther, Ph.D., Gynecological Research Laboratories, London, the article includes more than 100 co-authors. Funding for the study came from multiple private and government sources, including: Cancer Research UK, the Wellcome Trust, the Ovarian Cancer Research Fund, the Danish Cancer Society, Mermaid 1, Mayo Clinic, the National Cancer Institute, the American Cancer Society, U.S. Department of Defense, Canadian Institutes for Health Research, National Cancer Institute of Canada, Canadian Cancer Society, Lon V. Smith Foundation, the Eve Appeal, the OAK Foundation, National Health and Medical Research Council of Australia, Cancer Council of Tasmania, Cancer Foundation of Western Australia, ELAN Foundation, German Federal Ministry of Education and Research, Helsinki University Central Hospital Research Fund, Academy of Finland, and the Finnish Cancer Society.

Citation: Ellen L Goode, Georgia Chenevix-Trench, Honglin Song, Susan J Ramus, Maria Notaridou, Kate Lawrenson, Martin Widschwendter, Robert A Vierkant, Melissa C Larson, Susanne K Kjaer, Michael J Birrer, Andrew Berchuck, Joellen Schildkraut, Ian Tomlinson, Lambertus A Kiemeney, Linda S Cook, Jacek Gronwald, Montserrat Garcia-Closas, Martin E Gore, Ian Campbell, Alice S Whittemore, Rebecca Sutphen, Catherine Phelan, Hoda Anton-Culver, Celeste Leigh Pearce, 'A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24', Nature Genetics (2010) doi:10.1038/ng.668