Thursday, July 18, 2024

Brca Gene And Prostate Cancer

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How Does Genetic Testing Work

Metastatic Prostate Cancer: Testing for BRCA Mutations

Genetics can be instrumental in determining the likelihood that someone will develop prostate cancer. Anyone can request a germline genetic test from their primary care physician, which is typically conducted through either a blood draw or mouth swab. These tests can reveal whether you have a genetic mutation linked to an increased risk for various cancers, including prostate cancer.

Following a germline genetic test, you may be referred to a genetic counselor for more detailed testing or to review your results.

Patients who have been diagnosed with prostate cancer should also have the tumor itself tested in a process known as sematic genetic testing. This test should be conducted even if you have previously completed a germline genetic test, since existing tumors can evolve to carry the BRCA1 or BRCA2 mutations on their own. The tumor may do this because it is often beneficial for these cells to have certain defenses taken down so that it can multiply and mutate freely.

I Tested Positive On The Brca Test What Now

Euhus says that for patients diagnosed with a BRCA1 or BRCA2 gene mutation, careful, frequent and regular surveillance with their doctors can safeguard their health.

He and his team start screening such patients when they reach age 25. We do yearly MRIs to look for any signs of cancer, and add mammograms when the patient reaches age 30, he says.

For BRCA-positive patients who have completed childbearing and breastfeeding, prophylactic mastectomy is discussed. Depending on the patients specific mutation and other factors, this isnt always necessary.

When the patient reaches age 40, we consider surgery to remove the fallopian tubes and ovaries , since the risk of ovarian cancer is so much higher in these individuals, Euhus says. Surgery can prevent disease and significantly extend longevity.

Brca1/2 Mutations In Pancreatic Cancer

Pancreatic cancer is a disease with poor prognosis and low survival rates worldwide. Its mortality compares strikingly with its incidence. In the UK in 2011, there were 8,773 diagnosed cases and a mortality rate of 8,320 . Through analysis of the literature it was found that both BRCA1 and BRCA2 mutations are associated with the incidence of pancreatic cancer and that BRCA2 mutation poses an increased risk for developing pancreatic cancer . Furthermore environmental and genetic factors have been proposed as causes of the pancreatic cancer with the genetic factor of particular importance believed to be the BRCA2 gene .

It is clear that BRCA1/2 mutations are evident in many familial breast-pancreas cancer families and that carriers of the BRCA2 mutation have an increased risk of developing pancreatic cancer . Nonetheless, the degree to which family history of pancreatic cancer influences the likelihood of detecting a BRCA1/2 mutation in an individual with breast cancer is less clear . Perhaps, differences in population samples can account for conflicting results within studies making it difficult to make a connection. Furthermore, the use of different analysis models within studies can lead to variations in mutation prevalence.

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Hereditary Breast And Ovarian Cancer

About 5% to 10% of breast and 10% to 15% of ovarian cancers are hereditary. Hereditary cancer means cancer runs in your family, and could be caused by a change in certain genes that you inherited from your mother or father.

Genes act as instructions and contain information to build and maintain cells in the body. Humans inherit one set of genes from their mother and one set of genes from their father.

Genes are made up of DNA. DNA tells the body what traits will be passed on from parents to children, such as blood type, hair color, eye color, and risks of getting certain diseases.

What To Do If Youre Worried

Mutation BRCA et cancer de la prostate métastatique : impact ...

Speak to a GP if cancer runs in your family and youre worried you may get it too. They may refer you to a local genetics service for an NHS genetic test, which will tell you if you have inherited one of the cancer risk genes.

This type of testing is known as predictive genetic testing. Its predictive because a positive result means you have a greatly increased risk of developing cancer. It does not mean you have cancer or are definitely going to develop it.

You may be eligible for this NHS test if the faulty gene has already been identified in one of your relatives, or if there is a strong family history of cancer in your family.

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What A Positive Result Means

If your predictive genetic test result is positive, it means you have a faulty gene that raises your risk of developing cancer.

It does not mean you are guaranteed to get cancer your genes only partly influence your future health risks. Other factors, such as your medical history, lifestyle and your environment, also play a role.

If you have one of the faulty BRCA genes, there is a 50% chance you will pass this on to any children you have and a 50% chance that each of your siblings also has it.

You may want to discuss your results with other members of your family, who may also be affected. Staff at the genetics clinic will discuss with you how a positive or negative result will affect your life and your relationships with your family.

You can read more about BRCA1 and BRCA2 in the beginner’s guide to BRCA1 and BRCA2 produced by The Royal Marsden NHS Foundation Trust.

Insurance companies cannot ask you to disclose the results of predictive genetic tests for the majority of policies, but this may change in the future.

Inherited Cancer Risk: Brca Mutation

Can you inherit risk for breast cancer? Sometimes. Everyone has two types of breast cancer genes in every cell of their body. When functioning properly, BRCA1 and BRCA2 repair DNA, keep other genes healthy, and prevent cancerous changes in the cells.

When a mutation damages either of these genes, the persons risk of cancer increases. Inheriting damaged copies of the BRCA1 or BRCA2 genes can increase the risk for breast cancer and ovarian cancer in women and the risk for breast and prostate cancer in men, as well as other cancers.

David Euhus, M.D., Johns Hopkins Professor of Surgery, reviews what you need to know about genetic factors in breast cancer, who may be at risk, and how people with BRCA mutations can work with their doctors to guard against cancer.

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Does Health Insurance Cover The Cost Of Genetic Testing For Brca1 And Brca2 Variants

People considering BRCA1 and BRCA2 variant testing may want to confirm their insurance coverage for genetic counseling and testing. Genetic counselors can often help answer questions about insurance coverage for genetic testing.

Some genetic testing companies may offer testing for inherited BRCA1 and BRCA2 variants at no charge to patients who lack insurance and meet specific financial and medical criteria.

What Are Brca Genes

BRCA Testing and Prostate Cancer Treatment Decisions | Ask a Prostate Expert, Mark Scholz, MD

Every cell in your body has more than 25,000 genes. Each gene provides instructions for how to make certain proteins. These molecules help your cells work the right way.

Everyone has two copies of the BRCA1 and BRCA2 genes, or BReast CAncer gene 1 and BReast CAncer gene 2. You inherit a copy from each of your parents. But sometimes one of the gene pairs is damaged. You may hear these DNA errors called mutations or variants.

BRCA genes are known as âtumor-suppressorâ genes. They tell your body how to make proteins that repair cell damage. These genes play a big role in preventing cellular mistakes and killing cells that may promote cancer growth.

Gene defects make it harder to curb genes with cell changes that lead to cancer, or âoncogenes.â And BRCA gene mutations have a link to breast, ovarian, and prostate cancers. Research is looking into why these variants are associated with these specific cancers.

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Predictive Genetic Tests For Cancer Risk Genes

Cancer is not usually inherited, but some types mainly breast, ovarian, colorectal and prostate cancer can be strongly influenced by genes and can run in families.

We all carry certain genes that are normally protective against cancer. These genes correct any DNA damage that naturally happens when cells divide.

Inheriting faulty versions or “variants” of these genes significantly raises your risk of developing cancer, because the altered genes cannot repair the damaged cells, which can build up and form a tumour.

BRCA1 and BRCA2 are examples of genes that raise your cancer risk if they become altered. Having a variant BRCA gene greatly increases a woman’s chance of developing breast cancer and ovarian cancer. They also increase a man’s chance of developing male breast cancer and prostate cancer.

BRCA genes are not the only cancer risk genes. Researchers recently identified more than 100 new gene variants associated with an increased risk of breast, prostate and ovarian cancer. Individually, these new gene variants only slightly increase the risk of cancer, but a combination could mean a high risk overall.

If you or your partner have a high-risk cancer gene, such as an altered version of BRCA1, it can be passed on to any children you have.

Impact Of Brca1/2 Mutations In Other Associated Cancers

Previous studies have highlighted an association with BRCA1/2 gene mutations and an increased risk of developing cancer in sites other than the breast and ovary. The association of BRCA1/2 gene mutations with cancer of the prostate, pancreas and stomach has been demonstrated in a number of studies as discussed in this review. However, carcinomas of the colon and kidneys, as well as malignant melanoma, have also been reported to be linked with mutations in the BRCA1/2 genes . Nonetheless, the absolute risks for cancer developing at these other sites are small . The strengths of the associations may be difficult to estimate due to the lower reported incidence of these cancers in mutation carriers.

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Ethics Approval And Consent To Participate

Ethical clearance and approval of the study was sought from the institution review board of the School of Biomedical Science of Makerere College of Health Sciences . A reference number HDR-IRB-605 for the study was provided. Written consent to use the specimens of the patients included in this study was obtained from the chairperson of the IRB. The consent requires maintaining maximum confidentiality for the information of the patients whose specimens were used for the research as per guidelines for research stipulated by the institution which conform with the international guidelines for research including those of the Helsinki Declaration.

What Other Cancers Are Linked To Harmful Variants In Brca1 And Brca2

BRCA Gene Mutations Aren

Harmful variants in BRCA1 and BRCA2 increase the risk of several additional cancers. In women, these include fallopian tube cancer and primary peritoneal cancer , both of which start in the same cells as the most common type of ovarian cancer. Men with BRCA2 variants, and to a lesser extent BRCA1 variants, are also at increased risk of breast cancer and prostate cancer . Both men and women with harmful BRCA1 or BRCA2 variants are at increased risk of pancreatic cancer, although the risk increase is low .

In addition, certain variants in BRCA1 and BRCA2 can cause subtypes of Fanconi anemia, a rare syndrome that is associated with childhood solid tumors and development of acute myeloid leukemia . The mutations that cause these Fanconi anemia subtypes have a milder effect on protein function than the mutations that cause breast and ovarian cancer. Children who inherit one of these variants from each parent will develop Fanconi anemia.

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Screening For Other Cancers

People with a BRCA1 or BRCA2 mutation are not usually offered screening for other cancers. This is because:

  • the risk of other cancer types linked to BRCA1 or BRCA2 mutations is usually much lower than for breast cancer in women
  • regular screening tests cannot prevent these cancers
  • there is no clear evidence that screening tests for these cancers are good at finding cancer early when it is more treatable.

Sometimes screening for other cancer types is offered as part of a research trial. Taking part in a research trial is completely up to you. Your doctor or nurse can explain the possible risks and benefits of taking part.

Risk Of Aggressive Prostate Cancer

The pooled random-effects RRs of aggressive PCa were 1.98 for BRCA1 carriers and 6.08 for BRCA2 carriers . For BRCA2 carriers, the RR estimates differed significantly by the definition of aggressive PCa , with higher RR estimates reported for metastatic or Gleason score8 PCa than Gleason score7 PCa. For BRCA1, there was no significant heterogeneity by the definition of aggressive PCa . Restricted to estimates of the RR of Gleason score 7 PCa, the pooled random-effects RRs were 1.59 for BRCA1 carriers and 4.94 for BRCA2 carriers.

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The Impact Of Brca1/2 Mutations For Prostate Cancer

When BRCA1/2 mutations were discovered it was extensively reported that these mutations played a role in the development of breast and ovarian cancer. Since this advancement, considerable research has investigated whether BRCA1/2 mutations bestow risk of prostate cancer. Familial aggregation of prostate cancer has been described and the germline mutation of BRCA1/2 genes has been implicated in some research studies . To date, many have reported on the association of both BRCA1/2 mutations and some findings have indicated extensively lower rates of survival and more aggressive disease patterns .

It is recognised that some prostate cancer diagnoses have a poor prognosis and this has been connected with hereditary factors . The association between prostate cancer and BRCA2 is consistent within research. Several studies indicate that male carriers of BRCA2 are at an increased risk of developing prostate cancer while men with a BRCA1 mutation are believed to have a slightly higher risk of developing prostate cancer than those who possess no BRCA1/2 mutations. Early studies reported BRCA1 mutation carriers to have a significant increased relative risk of developing prostate cancer . Men who carry a mutated BRCA2 gene are reported to be seven times more likely to develop prostate cancer than men who do not possess the mutation

Cancer Screening And Medical Management

The Role of Genetic Testing for Inherited Prostate Cancer Risk

A personalized cancer risk management program can be developed for individuals known to be at increased cancer risk due to a mutation in BRCA1 or BRCA2. You and your doctors will ultimately decide what plan makes the most sense for you. Cancer risk management generally includes the following categories:

  • Intensive screening to increase the chances of early detection, should cancer develop.
  • Prophylactic or risk reducing surgical removal of breast tissue.
  • Chemoprevention, which is taking a medicine shown to lower the chances of developing cancer.

For men with BRCA1 or BRCA2 mutations, medical management typically begins at age 35. Your oncologist or primary care physician can help shape your specific screening plan.

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New Drugs Approved For Advanced Brca

  • By Charlie Schmidt, Editor, Harvard Medical School Annual Report on Prostate Diseases

Defective BRCA genes are well known for their ability to cause breast and ovarian cancers in women. But these same gene defects are also strong risk factors for aggressive prostate cancer in men. About 10% of men with metastatic prostate cancer meaning cancer that is spreading away from the prostate test positive for genetic mutations in BRCA genes. Fortunately, these cancers can be treated with new types of personalized therapies.

In May, the FDA approved two new drugs specifically for men with BRCA-positive metastatic prostate cancer that has stopped responding to other treatments. One of the drugs, called rucaparib, was approved on May 15. The other one, olaparib, was approved on May 19.

Both drugs work by shutting down the cancer cells ability to fix its DNA. Like all cells in the body, cancer cells are bombarded every day by free radicals, low-level radiation, and other stressors that cause DNA damage. BRCA genes ordinarily fix that damage so that cells can function normally and survive. But if the genes are defective, then the damage piles up. BRCA-positive tumors get around that problem by deploying an alternate DNA repair gene called PARP. Rucaparib and olaparib both inhibit PARP, leaving cancer cells without any way to fix their increasingly mangled DNA eventually the cells die.

Who Should Consider Genetic Counseling And Testing For Brca1 And Brca2 Variants

Anyone who is concerned about the possibility that they may have a harmful variant in the BRCA1 or BRCA2 gene should discuss their concerns with their health care provider or a genetic counselor.

Tests are available to see if someone has inherited a harmful variant in BRCA1 and BRCA2. However, testing is not currently recommended for the general public. Instead, expert groups recommend that testing be focused on those who have a higher likelihood of carrying a harmful BRCA1 or BRCA2 variant, such as those who have a family history of certain cancers. Testing can be appropriate for both people without cancer as well as people who have been diagnosed with cancer. If someone knows they have a mutation in one of these genes, they can take steps to reduce their risk or detect cancer early. And if they have cancer, the information about their mutation may be important for selecting treatment.

Before testing is done, a person will usually have a risk assessment, in which they meet with a genetic counselor or other health care provider to review factors such as which of their relatives had cancer, what cancers they had, and at what ages they were diagnosed. If this assessment suggests that someone has an increased risk of carrying a harmful BRCA1 or BRCA2 gene variant, their genetic counselor can discuss the benefits and harms of testing with them and order the appropriate genetic test, if the individual decides to have genetic testing .

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