Molecular Profiling Of Hereditary Breast Cancer
During the last decades, the microarray technology has been used extensively to study breast cancer biology. Numerous studies have used the platform for transcriptome and genomic profiling analyses, and recently, studies of genome-wide microRNA and methylations profiling have emerged. Microarray-based molecular profiling studies have uncovered the complexity and heterogeneity of breast cancer and established that breast cancer is not a single disease entity but rather a group of distinct disorders.
Although an exhaustible number of microarray profiling studies of breast cancers have been published, few studies analyzing hereditary breast cancers exist. Small sample sizes are a common denominator of most of the early studies that have been published. High-quality RNA and DNA are a prerequisite for conducting microarray analysis, wherefore access to frozen tumor tissue is necessary. The small study numbers can be explained by the fact that hereditary breast cancers account for only a minor fraction of breast cancer cases and access to frozen tumor tissue is often limited. Recently, several studies on larger cohorts using newer generations of microarray platforms have been published. In the following, the early and the more recent studies will be discussed. and represent overviews of the published transcriptome profiling studies and genomic profiling studies of hereditary breast cancers, respectively.
What This Means For Women At Risk Of Developing Hereditary Breast Cancer
Breastcancer.org, a non-profit organization committed to the mission of gathering information and creating a community for those affected by breast cancer, shares this information, Most people who develop breast cancer have no family history of the disease. However, when a strong family history of breast and/or ovarian cancer is present, there may be reason to believe that a person has inherited an abnormal gene linked to higher breast cancer risk. Some people choose to undergo genetic testing to find out. A genetic test involves giving a blood or saliva sample that can be analyzed to pick up any abnormalities in these genes.
Currently, the most common genetic tests for this disease are the BRCA1 and BRCA2 gene mutations. But as science introduces additional genetic variants linked to breast cancer, your healthcare provider may recommend further testing with a genetic counselor. If your personal or familial history suggests you could be a carrier of other genetic abnormalities, a more elaborate genetic panel may be of benefit to you. As advancements in the field of genetics continue, more accurate testing procedures will allow for earlier detection of breast cancer risk factors, a more individualized approach to care, and better treatment options.
Inheriting Certain Gene Changes
About 5% to 10% of breast cancer cases are thought to be hereditary, meaning that they result directly from gene changes passed on from a parent.
BRCA1 and BRCA2: The most common cause of hereditary breast cancer is an inherited mutation in the BRCA1 or BRCA2 gene. In normal cells, these genes help make proteins that repair damaged DNA. Mutated versions of these genes can lead to abnormal cell growth, which can lead to cancer.
- If you have inherited a mutated copy of either gene from a parent, you have a higher risk of breast cancer.
- On average, a woman with a BRCA1 or BRCA2 gene mutation has up to a 7 in 10 chance of getting breast cancer by age 80. This risk is also affected by how many other family members have had breast cancer.
- Women with one of these mutations are more likely to be diagnosed with breast cancer at a younger age, as well as to have cancer in both breasts.
- Women with one of these gene changes also have a higher risk of developing ovarian cancer and some other cancers.
- In the United States, BRCA mutations are more common in Jewish people of Ashkenazi origin than in other racial and ethnic groups, but anyone can have them.
Other genes: Other gene mutations can also lead to inherited breast cancers. These gene mutations are much less common, and most of them do not increase the risk of breast cancer as much as the BRCA genes.
Inherited mutations in several other genes have also been linked to breast cancer, but these account for only a small number of cases.
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Choosing Surgery To Prevent Breast Cancer
Ninan says women with BRCA1 or BRCA2 mutations face a significant risk of breast and ovarian cancer. Prophylactic removal of the fallopian tubes and ovaries is recommended by about age 40. Many women with BRCA1 or BRCA2 mutations will also elect to have their breasts removed. Nipple-sparing mastectomy is an effective option for these patients, she says.
Making the decision to have an elective preventive double mastectomy and removal of the ovaries is personal, and should be based on many life factors. You must balance where you are in your childbearing years, what your future choices may be, and whether you would prefer to follow a rigorous screening schedule instead of making such a life-altering choice.
If you are facing this decision, you are not alone. Caring specialists can ensure you have all the facts, and, if surgery is ultimately your choice, guide you in the appropriate breast surgery reconstruction to help restore your body image after treatment. If you are interested in discussing ovary removal surgery , your doctor can refer you to a specialist in gynecological oncology.
Are There Preventative Measures Women Can Take
Breastcancer.org recommends that women who are aware they have a genetic mutation linked to breast cancer consider implementing the following preventive measures to lessen the risk:
- Keep weight in a healthy range
- Engage in a regular exercise program
- Avoid smoking
- Consider reducing or eliminating alcohol
- Eat a nutrient-rich diet
More aggressive preventative strategies may include:
- Begin screening for hereditary breast cancer at an earlier age, depending on a woman’s family history
- Hormonal therapies
- A prophylactic mastectomy, or surgical removal of the healthy breasts
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Brca1 And Brca2 Genes
Everyone has BRCA1 and BRCA2 genes. BRCA stands for BReast CAncer gene. They are important genes that stop the cells in our body from growing and dividing out of control. Doctors call these tumour suppressor genes.
A fault in the BRCA1 or BRCA2 gene means that the cells can grow out of control. This can lead to cancer developing.
Faulty BRCA1 and BRCA2 genes are rare. Only around 1 in every 400 people have a faulty BRCA1 or BRCA2 gene.
Both men and women can have a faulty BRCA1 or BRCA2 genes. People who inherit faulty versions of these genes have an increased risk of developing different types of cancers. This includes:
Tests For Brca And Other Gene Mutations
A genetic test can tell you if you have any mutations in genes that are related to an increased risk of breast cancer. Its important to know that genetic testing is most helpful when you have a strong family history of either breast or ovarian cancer or a personal history of breast cancer.
If youd like to be tested, contact your doctor or your hospitals education office. Ask for a recommendation for a genetic counselor. Make an appointment and discuss the risks of undergoing genetic testing.
Your genes may affect your risk for breast cancer, but your lifestyle can have an impact as well. Whether or not you have a genetic mutation, its important to lower your risk whenever you can.
The following preventive measures may help you avoid a breast cancer diagnosis.
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Hereditary Papillary Renal Cancer
HPRC is a hereditary syndrome that increases the risk of a type of kidney cancer known as papillary type 1 kidney cancer, which is typically slow growing. Papillary kidney cancer forms in the cells lining the renal tubules.
HPRC is caused by mutations in the METgene. The MET gene makes a protein called MET that is involved in cell signaling and growth. When the MET gene is mutated, cells may not respond to signals that normally prevent them from growing, causing cancer to develop. Mutations in the MET gene are passed from parents to children. The syndrome caused by these mutations is inherited in an autosomal dominant fashion. If one parent has HPRC, there is a 50% chance for a child to inherit the mutation.
What Are The Estimated Cancer Risks Associated With Hboc
Cancer risks for women with HBOC
Lifetime risk of breast cancer 45% to 75%
Lifetime risk of ovarian cancer
BRCA1 gene mutation 25% to 40%
BRCA2 gene mutation 10% to 20%
Developing a second breast cancer 20% to 40%
Cancer risks for men with HBOC
Lifetime risk of breast cancer
BRCA1 gene mutation 1% to 2%
BRCA2 gene mutation 6%
BRCA1 gene mutation some increased risk
BRCA2 gene mutation 20%
Men with a BRCA2 gene mutation have a significantly increased risk of developing more aggressive prostate cancer before age 65 and therefore screening should begin at age 40.
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Having A Family History Of Breast Cancer
Its important to note that most women who get breast cancer do not have a family history of the disease. But women who have close blood relatives with breast cancer have a higher risk:
- Having a first-degree relative with breast cancer almost doubles a womans risk. Having 2 first-degree relatives increases her risk by about 3-fold.
- Women with a father or brother who has had breast cancer also have a higher risk of breast cancer.
What Is Hereditary Breast And Ovarian Cancer
A diagnosis of Hereditary Breast and Ovarian Cancer Syndrome is considered when there are multiple cases of breast cancer and/or ovarian cancer on the same side of the family. The chance that a family has HBOC increases in any of these situations:
1 or more women are diagnosed at age 45 or younger
1 or more women are diagnosed with breast cancer before age 50 with an additional family history of cancer, such as prostate cancer, melanoma, and pancreatic cancer
There are breast and/or ovarian cancers in multiple generations on the same side of the family, such as having both a grandmother and an aunt on the fathers side both diagnosed with these cancers
A woman is diagnosed with a second breast cancer in the same or the other breast or has both breast and ovarian cancers
A male relative is diagnosed with breast cancer
There is a history of breast cancer, ovarian cancer, prostate cancer, and/or pancreatic cancer on the same side of the family
Having Ashkenazi Jewish ancestry
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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 .
What To Do If A Person Is Concerned About Their Risk
If a person is concerned that they may have inherited a breast cancer gene, they should speak with a doctor. A doctor may suggest for a person to undergo genetic counseling.
Genetic counseling involves a person speaking with a genetic counselor about their chances of developing breast cancer. Genetic counselors can also provide a person with resources and support.
This type of counseling can also help a person decide if they would like to take part in genetic testing or not. Genetic testing involves checking a persons genetic profile for breast cancer-causing genes.
Genetic testing for cancer usually involves a person submitting a blood sample. However, other forms of genetic testing can use cell samples from a persons:
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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.
Possible Low Penetrance And Modifier Genes Implicated In Breast Cancer
As noted above, inheriting a mutated allele of a breast cancer susceptibility gene is associated with a high probability of developing breast cancer. The high penetrance of these tumor-suppressor genes results in so-called cancer pedigrees, large families with multiple affected members whose analysis has led to genetic linkage and subsequent isolation of these genes, including BRCA1 and BRCA2. In contrast, other genes have been predicted in which mutations might result in a more moderate increase in breast cancer risk. These postulated genes might have a low penetrance and thus act to modify or enhance other risk factors for breast cancer. While mutations in low penetrance genes would not be expected in breast cancer pedigrees, such mutations might be relatively common and hence play an important role in genetic predisposition to breast cancer within the general population. The first potentially common, low penetrance breast cancer gene to be tested is the ataxia telangiectasia gene. While its actual contribution to breast cancer is uncertain, other low penetrance genes that contribute to the development of breast cancer will undoubtedly emerge.
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Kidney Cancer Is A Disease In Which Malignant Cells Form In Tubules Of The Kidney
Kidney cancer is a disease in which malignant cells are found in the lining of tubules in the kidney. There are 2 kidneys, one on each side of the backbone, above the waist. Tiny tubules in the kidneys filter and clean the blood. They take out waste products and make urine. The urine passes from each kidney through a long tube called a ureter into the bladder. The bladder holds the urine until it passes through the urethra and leaves the body.
Cancer that starts in the ureters or the renal pelvis is different from renal cell cancer and is not associated with the hereditary syndromes described in this summary. Cancer of the renal pelvis may be associated with another hereditarycondition called Lynch syndrome.
Whether A Person Should Get Tested For Hereditary Kidney Cancer Depends On Certain Factors
Certain clues in a person’s medical history or family history may lead health professionals to think that an individual may have a hereditary syndrome. These individuals may benefit from genetic counseling and genetic testing. With kidney cancer, individuals who have one or more of the following criteria may be referred for genetic testing:
- Multiple family members have had kidney cancer.
- Cancer developed at a young age.
- Multiple tumors in one kidney or cancer in both kidneys.
- Diagnosis of a type of kidney cancer that is known to be commonly inherited.
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Hereditary Leiomyomatosis And Renal Cell Cancer
HLRCC is a hereditary syndrome that increases the risk of kidney cancer. HLRCC is associated with a unique type of kidney cancer that can be fast growing and may lead to different treatment decisions. People with HLRCC can also develop skin lesions known as leiomyomas and uterinefibroids .
HLRCC is caused by mutations in the FHgene. The FH gene makes a protein called fumarase. Fumarase helps cells use oxygen and produce energy. When the FH gene is mutated, cells are not able to use oxygen, which may lead to cancer. These mutations are passed from parents to children. The syndrome caused by these mutations is inherited in an autosomal dominant fashion. If one parent has HLRCC, there is a 50% chance for a child to inherit the mutation.
Learn more about HLRCC from the NCATS Genetic and Rare Diseases Information Center.