From the Research
A BRIP1 pathogenic mutation c.484C>T significantly increases the risk of developing certain cancers, particularly ovarian cancer, with a recommended enhanced surveillance and consideration of risk-reducing salpingo-oophorectomy after completion of childbearing or by age 45-50. Women with this mutation have approximately a 6-8% lifetime risk of ovarian cancer, which is 3-4 times higher than the general population risk. This specific mutation creates a premature stop codon in the BRIP1 gene, resulting in a truncated, non-functional protein that cannot properly interact with BRCA1 to repair damaged DNA. The BRIP1 gene normally helps repair breaks in DNA, and when mutated, cells accumulate DNA damage that can lead to cancer development.
Key Points
- The BRIP1 gene is involved in DNA double-strand break repair, and mutations in this gene can increase the risk of ovarian cancer 1, 2.
- A study published in 2022 found that a dominant-negative pathogenic variant BRIP1 c.1045G>C is a high-risk allele for non-mucinous epithelial ovarian cancer, with an odds ratio of 140.8 for EOC 3.
- Another study published in 2020 found that rare BRIP1 missense alleles confer risk for ovarian and breast cancer, with 75% of characterized variants demonstrating loss-of-function activity 4.
- However, a study published in 2016 found that protein truncating variants in BRIP1 are not associated with a substantial increase in breast cancer risk, suggesting that BRIP1 mutations are not strongly associated with increased breast cancer risk 5.
Management Options
- Enhanced surveillance is recommended for individuals with a BRIP1 pathogenic mutation, including consideration of risk-reducing salpingo-oophorectomy after completion of childbearing or by age 45-50.
- Genetic counseling is essential for individuals with this mutation to understand their specific risks and management options, and cascade testing should be offered to blood relatives who may also carry this mutation.
- The management of BRIP1 mutations should prioritize the reduction of ovarian cancer risk, given the higher association of these mutations with ovarian cancer compared to breast cancer.