March 29, 2013 | by Shawn Le
While it is well-established that mutations in the two BRCA genes increase breast and ovarian cancer risks, the exact level of elevated risk is a little fuzzier. For a BRCA gene mutation carrier, the risk of getting breast and ovarian cancer in her lifetime ranges from 40 to 70 percent and 15 to 40 percent, respectively.
With women taking drastic measures, including removing their own breasts and ovaries regardless of whether they were ever diagnosed with cancer, a better understanding of that risk could help them make more well-informed decisions to maintain their health and quality of life.
And researchers from more than 280 hospitals and institutions, including City of Hope, are looking into refining those risk probabilities.
In a paper published in the journal PLOS Genetics on March 27, researchers from a consortium called the Collaborative Oncological Gene-environment Study (COGS) identified 74 specific variations in the BRCA genes and how they greatly impact the risk of women developing breast and ovarian cancers.
Jeffrey Weitzel. M.D., chief of City of Hope’s Division of Clinical Cancer Genetics, and Susan Neuhausen, Ph.D., the Morris & Horowitz Families Professor in Cancer Etiology and Outcomes Research at City of Hope, are among the members of COGS involved in this study.
The research team conducted a genome-wide association study that analyzed the genetic profile of 11,705 women who carried the BRCA1 mutation. Of those women, 5,920 had been diagnosed with breast cancer and 1,839 were diagnosed with ovarian cancer. The analysis revealed that for BRCA1 mutation carriers, one specific gene location known as 1q32 modified breast cancer risk and two gene locations known as 17q21.31 and 4q32.3 affected ovarian cancer risk.
BRCA1 mutation carriers who also have the highest risk variation of the 1q32 gene face a 81 to 100 chance of getting breast cancer in their lifetimes, versus 28 to 50 percent for those with the lowest risk variants. Similarly, those at highest risk for ovarian cancer with either of those two gene variations may see a 63 percent or higher lifetime risk, as opposed to 28 percent or lower for the lowest risk group.
The paper’s authors wrote: “Such differences in risk may have important implications for the risk prediction and clinical management of BRCA1 carriers.” The more physicians know about the specific risks women carrying the BRCA1 mutation face – and the probability of those risks developing – the better precautions they can recommend in lifestyle changes, preventive medication and other therapies that are better tailored to the individual person.