A genetic mutation, or pathogenic variant, is a permanent change in the DNA sequence that can affect how a gene functions. These changes sometimes predispose an individual to hereditary cancers. The BRIP1 gene plays a role in inherited cancer risk, particularly for ovarian cancer. Understanding the frequency of this mutation is important for assessing its impact and informing genetic testing strategies. This article examines how common the BRIP1 mutation is across different populations.
The Role of the BRIP1 Gene
The BRIP1 gene produces a protein that acts as a DNA helicase. This protein is a component of the mechanism cells use to repair damaged DNA, specifically double-strand breaks. The BRIP1 protein works closely with other repair proteins, including BRCA1, to facilitate homologous recombination.
This intricate repair pathway maintains the stability of the entire genome. A mutation in the BRIP1 gene disrupts this mechanism, leading to a faulty or non-functional protein. When DNA damage occurs, a carrier’s cells cannot repair the breaks efficiently, allowing errors to accumulate and increasing the chance of cancer.
Global Prevalence of the Mutation
The BRIP1 mutation is considered rare in the general population, with studies estimating the carrier frequency to be very low. In control populations without a history of associated cancers, the prevalence of a pathogenic BRIP1 variant is less than 0.1%. This low frequency categorizes the BRIP1 mutation as a moderate-penetrance gene, conferring a lower risk than high-penetrance genes like BRCA1 and BRCA2.
The frequency is notably higher when examining patients already diagnosed with ovarian cancer. Studies show that a BRIP1 mutation is present in approximately 0.72% to 0.92% of unselected ovarian cancer cases. This means that nearly one in every 100 women diagnosed with ovarian cancer may have an underlying inherited BRIP1 mutation.
The prevalence differs for women with a strong family history of cancer who test negative for BRCA1 and BRCA2 mutations. In this high-risk group, the BRIP1 mutation is one of the more commonly found genetic changes. This contrast highlights the significance of the mutation in hereditary cancer predisposition.
Cancer Risk Associated with BRIP1
Carrying a pathogenic BRIP1 mutation is primarily associated with a moderately increased lifetime risk of developing ovarian cancer. For women with the mutation, the estimated lifetime risk falls within a range of approximately 5% to 15%. This risk is significantly higher than the 1.1% to 1.3% risk for the average woman in the general population.
The mutation is classified as conferring a moderate risk, which is lower than the risk associated with BRCA1 or BRCA2 mutations.
The association between BRIP1 and breast cancer risk is less clear and remains a topic of ongoing research. Some data suggests a possible modest increase in risk, while other large studies have found no significant association. Due to this conflicting evidence, the increased risk for breast cancer is often considered uncertain or low, though individual risk assessment depends on personal and family history.
Inheriting and Detecting the BRIP1 Mutation
The BRIP1 mutation is inherited in an autosomal dominant pattern. This means inheriting only one copy of the altered gene from one parent is sufficient to be a carrier. A parent who carries the mutation has a 50% chance of passing it to each child, regardless of sex.
Genetic testing for the BRIP1 mutation is performed on a blood or saliva sample to analyze the germline DNA. Testing is recommended for individuals with a strong personal or family history of ovarian or breast cancer. This is especially true if they have already tested negative for BRCA1 and BRCA2 mutations. Identifying the mutation allows for a personalized assessment of cancer risk for the individual and their relatives.