Related Experiment Video
Updated: Jul 21, 2025
In Vivo and Ex Vivo Approaches to Study Ovarian Cancer Metastatic Colonization of Milky Spot Structures in Peritoneal Adipose
Published on: October 14, 2015
Germline Mutations in 12 Genes and Risk of Ovarian Cancer in Three Population-Based Cohorts
Joanne Kotsopoulos1,2, Cassandra A Hathaway3, Steven A Narod1,2
1Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada.
Background:
With the widespread use of multigene panel genetic testing, population-based studies are necessary to accurately assess penetrance in unselected individuals. We evaluated the prevalence of germline pathogenic or likely pathogenic variants (mutations) in 12 cancer-predisposition genes and associations with ovarian cancer risk in three population-based prospective studies [Nurses' Health Study (NHS), NHSII, Cancer Prevention Study II].
Methods:
We included women with epithelial ovarian or peritoneal cancer (n = 776) and controls who were alive and had at least one intact ovary at the time of the matched case diagnosis (n = 1,509). Germline DNA was sequenced for mutations in 12 genes. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for ovarian cancer risk by mutation status.
Results:
The mutation frequency across all 12 genes was 11.2% in cases and 3.3% in controls (P < 0.0001). BRCA1 and BRCA2 were the most frequently mutated (3.5% and 3.8% of cases and 0.3% and 0.5% of controls, respectively) and were associated with increased ovarian cancer risk [OR, BRCA1 = 12.38; 95% confidence interval (CI) = 4.72-32.45; OR, BRCA2 = 9.18; 95% CI = 3.98-21.15]. Mutation frequencies for the other genes were ≤1.0% and only PALB2 was significantly associated with risk (OR = 5.79; 95% CI = 1.09-30.83). There was no difference in survival for women with a BRCA germline mutation versus no mutation.
Conclusions:
Further research is needed to better understand the role of other mutations in ovarian cancer among unselected populations.
Impact:
Our data support guidelines for germline genetic testing for BRCA1 and BRCA2 among women diagnosed with epithelial ovarian cancer; testing for PALB2 may be warranted.
More Related Videos
08:15gDNA Enrichment by a Transposase-based Technology for NGS Analysis of the Whole Sequence of BRCA1, BRCA2, and 9 Genes Involved in DNA Damage Repair
Published on: October 6, 2014
09:08Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Related Concept Videos
02:21Cancers Originate from Somatic Mutations in a Single Cell
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:59Cancer Prevention
Some...
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:20Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...