BRCA1 and BRCA2 are two of the best-studied genes linked to hereditary breast and ovarian cancer. In Pakistan, where breast and ovarian cancer rates are among the highest reported in Asia, several research groups have looked specifically at how often BRCA1 and BRCA2 mutations show up in Pakistani patients, and which specific gene changes tend to recur. This article walks through what’s actually been found, what BRCA genetic testing can and can’t tell someone, and how the process typically works from testing through counselling.
What Are BRCA1 and BRCA2 Genes?
BRCA1 and BRCA2 are tumor suppressor genes. Their normal job is to help repair damaged DNA inside cells, which keeps cell division under control and prevents damaged cells from multiplying unchecked. Everyone has two working copies of each gene, one inherited from each parent.
When a person inherits a harmful change in one copy of BRCA1 or BRCA2, that DNA-repair process becomes less reliable over a lifetime. This doesn’t cause cancer directly, but it raises the chances that cells in certain tissues, mainly breast and ovarian tissue, accumulate enough additional damage over time to become cancerous.
What Are BRCA1 and BRCA2 Pathogenic Variants?
In genetics, the more precise term for a harmful gene change is a pathogenic variant rather than simply a mutation, since not every variant found in a gene actually causes disease. Some variants are harmless, some have an unclear effect (called a variant of uncertain significance), and some are clearly disease-causing.
It’s also worth distinguishing two very different contexts where BRCA testing comes up:
- Germline (inherited) testing looks for a variant present in every cell of the body, inherited from a parent and potentially passable to children. This is what’s usually meant by BRCA genetic testing.
- Somatic (tumor) testing looks for changes that occurred only within cancer cells themselves, not inherited and not passed on to children. This is sometimes done to help guide treatment once cancer is already diagnosed.
The rest of this article focuses on germline testing, since that’s what’s relevant to assessing inherited cancer risk.
BRCA Mutations Reported in Pakistani Patients
Several research groups have studied BRCA1 and BRCA2 in Pakistani patients, and it’s worth understanding why their reported numbers differ, since the answer depends heavily on which patients were studied.
One case-control study of unselected breast and ovarian cancer patients from Karachi and Lahore found a BRCA1 or BRCA2 mutation in about 6.7% of breast cancer patients and about 15.8% of ovarian cancer patients, compared with none of the healthy controls tested (Liede et al., American Journal of Human Genetics, 2002). In that study, BRCA1 accounted for the large majority of mutations found, and most of the specific variants identified had not been reported outside Pakistan.
A separate, larger study focused specifically on patients selected for a strong family history of breast or ovarian cancer, or for early age at diagnosis, since these features raise the likelihood of finding an inherited mutation. Among more than 500 such Pakistani families, a pathogenic BRCA1 or BRCA2 variant was identified in roughly a quarter of cases overall, rising to just over half of families that included both breast and ovarian cancer. BRCA1 mutations were found to be about five times more common than BRCA2 mutations in this group, findings that are directly relevant to how oncology diagnostics approach hereditary cancer risk assessment (Rashid et al., Hereditary Cancer in Clinical Practice, 2019).
These two studies illustrate an important point: the percentage of patients found to carry a BRCA mutation depends heavily on how they were selected. Numbers from patients chosen for strong family history will always look higher than numbers from an unselected group of cancer patients, and neither figure should be treated as a single, fixed Pakistani BRCA rate.
As for which specific variants turn up most often, the larger 2019 study found that a relatively small number of recurring BRCA1 and BRCA2 variants accounted for most of the mutations detected, and that many of these were specific to particular ethnic communities within Pakistan, such as Punjabi, Pathan, and Balochi groups. This pattern, where a mutation becomes common within a specific community because of shared ancestry rather than arising independently many times, is known as a founder effect, and it’s a recurring theme across the published research on this topic. Internationally well-known founder mutations, such as the one often labeled 5382insC, have occasionally turned up in Pakistani patients too, but they are not among the mutations most frequently identified in the largest Pakistani studies to date. Because the recurring variants differ meaningfully between ethnic groups and even between studies, a Pakistani patient’s actual result depends on their own testing, not on a single most common mutation that applies nationally.
How Are BRCA1 and BRCA2 Variants Identified?
Genetic testing is the only definitive way to confirm whether someone carries a BRCA1 or BRCA2 pathogenic variant. But a few clinical clues commonly prompt a doctor to suggest testing in the first place:
- Personal cancer history — particularly breast or ovarian cancer diagnosed at a younger age than typical.
- Family history — multiple relatives with breast, ovarian, pancreatic, or prostate cancer, especially across more than one generation.
- Cancer type — triple-negative breast cancer (a subtype that doesn’t rely on estrogen, progesterone, or HER2 receptors) is more often linked to BRCA1 variants, while male breast cancer is more often linked to BRCA2.
- Multiple primary cancers in the same person, or breast and ovarian cancer both appearing in one family.
None of these factors alone confirms a BRCA mutation; they’re simply patterns that make testing more likely to be informative. A genetic counsellor or oncologist is best placed to weigh a person’s specific history and decide whether testing makes sense.
What Does BRCA Genetic Testing Involve, and What Do Results Mean?
Germline BRCA testing typically uses a blood or saliva sample and looks specifically at the sequence of the BRCA1 and BRCA2 genes for pathogenic variants, one part of the broader range of diagnostic specialties available for assessing inherited health risks. A result generally falls into one of three categories:
- Positive. A known pathogenic variant was found. This means the person has an inherited, elevated risk of certain cancers compared with the general population — it does not mean cancer is certain, and many carriers never develop cancer.
- Negative. No pathogenic variant was found in BRCA1 or BRCA2. This is reassuring, but it doesn’t rule out all inherited cancer risk, since other genes can also contribute to hereditary cancer, particularly if a strong family history remains unexplained.
- Variant of uncertain significance (VUS). A change was found, but current evidence isn’t enough to classify it as harmful or harmless. This result usually doesn’t change medical management on its own and may be reclassified as more evidence becomes available.
BRCA Mutations and Cancer Risk
Carrying a pathogenic BRCA1 or BRCA2 variant raises lifetime risk of breast and, particularly for BRCA1, ovarian cancer well above the general population’s baseline risk. BRCA2 variants are additionally associated with a higher risk of male breast cancer and have been linked to increased risk of certain other cancers, including prostate and pancreatic cancer, in some studies. Because breast and ovarian cancer risk sits at the center of this discussion, it’s an area where gynecology services and oncology care often work together with genetic testing to guide a woman’s ongoing monitoring.
Exactly how much a specific variant raises risk can vary by the particular gene change, family history, and other factors, so individual risk is best discussed with a genetic counsellor or oncologist rather than estimated from a general percentage. What’s consistent across the research is that a positive result changes a person’s risk category meaningfully, without making any individual outcome certain.
Managing Risk After a Positive Result
For people who test positive for a BRCA1 or BRCA2 pathogenic variant, management is usually built around a few approaches, often used in combination and tailored to the individual:
- Enhanced screening and surveillance — such as more frequent mammograms, breast MRI, and transvaginal ultrasound, aimed at catching any cancer at an earlier, more treatable stage.
- Risk-reducing surgery — some individuals choose prophylactic mastectomy or removal of the ovaries and fallopian tubes to substantially lower their cancer risk, a decision usually made after detailed counselling.
- Chemoprevention — certain medications may be considered in specific situations to help lower breast cancer risk.
- Treatment-relevant information — for those who do develop cancer, knowing BRCA status can influence which treatments are considered, since some therapies are specifically more effective against BRCA-related tumors.
None of these decisions are one-size-fits-all, and the right path depends on personal risk tolerance, family history, age, and reproductive plans, discussed together with a treating physician.
Genetic Counselling and Family Testing
Genetic counselling is a core part of the BRCA testing process, both before and after a test is done. Before testing, a counsellor can help someone understand what a result might mean and whether testing is likely to be informative given their history. After testing, counselling helps translate a lab report into practical next steps.
When a pathogenic variant is confirmed in one family member, first-degree relatives (parents, siblings, children) are often offered testing for that same, already-identified variant, a process sometimes called cascade testing. Because the exact familial variant is already known, this follow-up testing is usually more straightforward and focused than the original test. Anyone considering this next step for themselves or a relative can get in touch with ELC Biogen’s team to ask about the process.
BRCA Testing vs a Broader Hereditary Cancer Panel
BRCA1 and BRCA2 are the two genes most strongly associated with hereditary breast and ovarian cancer, but they’re not the only ones. A broader hereditary cancer panel tests additional genes (such as PALB2, TP53, CHEK2, and others depending on the lab) that have also been linked to increased cancer risk.
A wider panel may be considered when family history strongly suggests a hereditary pattern but BRCA1/BRCA2 testing alone comes back negative, or when a family’s pattern of cancers doesn’t point specifically to BRCA. Whether BRCA-only testing or a broader panel is more appropriate depends on personal and family history, which is exactly the kind of decision genetic counselling is designed to help with. Teams that work across ELC Biogen’s diagnostic specialties, from oncology to reproductive health, are generally well placed to help weigh this decision alongside a patient’s treating physician.
Readers who want to learn more about ELC Biogen’s genetic and molecular diagnostic services more broadly can explore what’s available at elcbiogen.com.
Frequently Asked Questions
What is a BRCA test?
It’s a genetic test that looks for inherited pathogenic variants in the BRCA1 and BRCA2 genes, which are linked to a higher risk of breast and ovarian cancer.
Who should consider BRCA genetic testing?
People with a personal or family history of early-onset breast or ovarian cancer, multiple affected relatives, male breast cancer in the family, or a known BRCA variant in a relative are often considered candidates, ideally after a discussion with a genetic counsellor or oncologist.
What does a positive BRCA test mean?
It means a pathogenic variant was found, and the person’s lifetime risk of certain cancers is higher than average. It does not mean cancer is guaranteed to develop.
Does a BRCA mutation mean I will develop cancer?
No. It raises the likelihood significantly, but many people with a BRCA pathogenic variant never develop cancer, and risk-reducing options can lower that likelihood further.
Can family members be tested for the same BRCA variant?
Yes. Once a specific variant is identified in one family member, close relatives can be tested for that exact variant, which is usually a simpler, more targeted test.
What is the difference between BRCA testing and a hereditary cancer panel?
BRCA testing looks only at BRCA1 and BRCA2. A hereditary cancer panel tests several additional genes linked to cancer risk and may be recommended when BRCA testing alone doesn’t explain a family’s cancer history.
Is BRCA testing useful if there is no family history of cancer?
It can still be relevant in specific situations, such as certain cancer subtypes diagnosed at a young age, but testing decisions in the absence of family history are usually made case by case with a genetic counsellor or oncologist.