Cancer Genetics Mutations Hereditary
Breast
About 5% to 10% of breast cancers are thought to be hereditary, caused by abnormal genes passed from parent to child. Most inherited cases of breast cancer are associated with mutations in two genes: BRCA1 (BReast CAncer gene one) and BRCA2 (BReast CAncer gene two).
Women who have a BRCA1 mutation or BRCA2 mutation (or both) can have up to a 72% risk of being diagnosed with breast cancer during their lifetimes. Breast cancers associated with a BRCA1 or BRCA2 mutation tend to develop in younger women and occur more often in both breasts than cancers in women without these genetic mutations. Women with a BRCA1 or BRCA2 mutation also have an increased risk of developing ovarian, colon, and pancreatic cancers, as well as melanoma. Men who have a BRCA2 mutation have a higher risk of breast cancer than men who don’t — about 8% by the time they’re 80 years old. This is about 80 times greater than average.
Genetics (breastcancer.org)
**********************
Up to 10% of breast cancers may be hereditary, meaning they are caused by a genetic mutation inherited from a parent. Three of the most well-known genes that can mutate and raise the risk of breast cancer are BRCA1, BRCA2, and PALB2. People who inherit a mutation in any of these genes from their mothers or fathers have a higher-than-average lifetime risk of developing breast cancer, ovarian cancer, or certain other cancers. Normally, the BRCA and PALB2 genes keep breast cells growing normally and prevent cancer cell growth. But when these genes contain mutations that are passed from generation to generation, they stop functioning normally and increase the risk of breast and other cancers.
Sources:
[Note: BRCA, which is short for BReast CAncer, is usually pronounced by saying the names of the four letters: B-R-C-A.]
Inherited mutations in the following genes also increase the risk of breast cancer:
- ATM
- BARD1
- CDH1
- CHEK2
- NF1
- PALB2
- PTEN
- RAD51C
- RAD51D
- STK11
- TP53
For more information about these genes, see “Inherited Gene Mutations” on the Susan G. Komen website
Inherited genetic mutations that increase the risk of breast cancer
About 5% to 10% of breast cancer cases are thought to be hereditary, meaning that they result directly from gene changes (mutations) passed on from a parent. 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.
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. 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. Men who inherit one of these gene changes also have a higher risk of breast and some other cancers.
In the United States, BRCA mutations are more common in Jewish people of Ashkenazi (Eastern Europe) origin than in other racial and ethnic groups, but anyone can have them. 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.
- ATM
- PALB2
- TP53
- CHEK2
- PTEN
- CDH1
- STK11
Source: “Inheriting certain gene changes” (American Cancer Society)
Certain gene mutations increase the risk of Triple-Negative Breast Cancer (TNBC)
Mutations in the following genes have been linked to increased risk for breast cancer in women:
- ATM
- BARD1 (especially triple-negative breast cancer)
- BRCA1 (frequently linked to triple-negative breast cancer)
- BRCA2
- CDH1 (frequently linked to lobular breast cancer)
- CHEK2
- NF1 (only in people with neurofibromatosis)
- PALB2
- PTEN
- RAD51C (especially triple-negative breast cancer)
- RAD51D (especially triple-negative breast cancer)
- STK11
- TP53
Mutations in the following genes may also be linked to increased breast cancer risk, but more research is needed to confirm this.
- BRIP1 (especially triple-negative breast cancer)
- NBN (only in people with a 657del5 mutation)
Mutations in the following genes have been linked to breast cancer risk in men:
- BRCA1
- BRCA2
- CHEK2
- PALB2
Source: “Genes with inherited mutations linked to breast cancer” (FORCE: Facing Hereditary Cancer Empowered)
Hereditary Breast & Colon Cancer Mgmt for Clinicians
https://www.youtube.com/watch?v=lSfdbUmRSP8
Cervical
Hereditary cervical cancer?
Most common types of cervical cancer are not hereditary. In fact, around 70%Trusted Source of cervical cancers are due to infection with human papillomavirus (HPV). However, some very rare types of cervical cancer can be hereditary, meaning they have a genetic component. In these cases, a person may be at risk of developing such cancers if they have a genetic variant that increases their risk of developing cervical cancer or a first-degree relative with cervical cancer linked to a genetic cause.
There are two main genetic risk factors for cervical cancer: DICER1 syndrome and Peutz-Jeghers syndrome (PJS).
Cervical cancer: Is it genetic? (medicalnewstoday.com)
*************************
Cervical cancer may run in some families. If your mother or sister had cervical cancer, your chances of developing the disease are higher than if no one in the family had it. Some researchers suspect that some rare instances of this familial tendency are caused by an inherited condition that makes some women less able to fight off HPV infection than others.
In other instances, women in the same family as a patient already diagnosed could be more likely to share one or more of other non-genetic risk factors.
Source: Risk Factors for Cervical Cancer (American Cancer Society, 2020)
Colorectal
About 5% of people who develop colorectal cancer have inherited gene changes (mutations) that cause family cancer syndromes and can lead to them getting the disease. The most common inherited syndromes linked with colorectal cancers are Lynch syndrome (hereditary non-polyposis colorectal cancer, or HNPCC) and familial adenomatous polyposis (FAP), but other rarer syndromes can increase colorectal cancer risk, too.
Colorectal Cancer Risk Factors | Hereditary Colorectal Risk Factors
**********************************
The most common inherited syndromes linked with colorectal cancers are Lynch syndrome (hereditary non-polyposis colorectal cancer, or HNPCC) and familial adenomatous polyposis (FAP), but other rarer syndromes can increase colorectal cancer risk, too.
Approximately 5 to 10 percent of colon cancer is hereditary. The major hereditary colon cancer syndromes are Lynch syndrome (previously known as Hereditary Non-Polyposis Colorectal Cancer or HNPCC) and Familial Adenomatous Polyposis (FAP). Other genes have also been implicated in hereditary colon cancer risk.
Hereditary Breast & Colon Cancer Mgmt for Clinicians
https://www.youtube.com/watch?v=lSfdbUmRSP8
Multiple genes are associated with hereditary colon cancer, but mutations in genes associated with Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM) are the most common cause of the hereditary form of the disease. Prediction models can estimate an individual’s risk for a Lynch syndrome mutation.
Additional information on colon cancer predisposition genes can be found on the Hereditary Colon Cancer Gene List listed below.
Approximately 25 to 35 percent of colon cancer is familial, meaning the disease occurs more often in family members than can be expected in the general population even though a particular gene mutation has not been identified in the family. With familial colon cancer, the specific cause of colon cancer is unknown but likely due to combinations of risk factors including genetics, lifestyle, and environment that increase risk in the family.
https://utswmed.org/conditions-treatments/genetics-and-hereditary-cancers/guide-hereditary-cancer-health-pros/hereditary-colon-cancer-guide-health-pros/
A very small portion of colorectal cancers are caused by inherited gene mutations. Many of these DNA changes and their effects on the growth of cells are now known. For example:
Familial adenomatous polyposis (FAP), attenuated FAP (AFAP), and Gardner syndrome are caused by inherited changes in the APC gene. The APC gene is a tumor suppressor gene; it normally helps keep cell growth in check. In people with inherited changes in the APC gene, this “brake” on cell growth is turned off, causing hundreds of polyps to form in the colon. Over time, cancer will nearly always develop in one or more of these polyps.
Lynch syndrome (hereditary non-polyposis colon cancer, or HNPCC) is caused by changes in genes that normally help a cell repair damaged DNA. A mutation in one of the DNA repair genes like MLH1, MSH2, MSH6, PMS2, and EPCAM, can allow DNA errors to go unfixed. These errors will sometimes affect growth-regulating genes, which may lead to the development of cancer.
Peutz-Jeghers syndrome is caused by inherited changes in the STK11 (LKB1) gene, a tumor suppressor gene.
MUTYH-associated polyposis (MAP) is caused by mutations in the MUTYH gene, which is involved in how the cell “proofreads” or checks the DNA and fixes errors when cells divide.
https://www.cancer.org/cancer/colon-rectal-cancer/causes-risks-prevention/what-causes.html
Endometrial
Endometrial cancer tends to run in some families. Some of these families also have a higher risk for colon cancer. This disorder is called hereditary nonpolyposis colon cancer (HNPCC). Another name for HNPCC is Lynch syndrome. In most cases, this disorder is caused by a defect in either the mismatch repair gene MLH1 or the gene MSH2. But at least 5 other genes can cause HNPCC: MLH3, MSH6, TGBR2, PMS1, and PMS2. An abnormal copy of any one of these genes reduces the body’s ability to repair damage to its DNA or control cell growth. This results in a very high risk of colon cancer, as well as a high risk of endometrial cancer. Women with this syndrome have a up to a 70% risk of developing endometrial cancer at some point. (The risk for women in general is about 3%.) The risk of ovarian cancer is also increased. General information about inherited cancer syndromes can be found in Family Cancer Syndromes.
Some families have a higher rate of only endometrial cancer. These families may have a different genetic disorder that hasn’t been found yet.
https://www.cancer.org/cancer/endometrial-cancer/causes-risks-prevention/risk-factors.html
DNA repair defects
Sometimes, endometrial cancer may seem to “run in a family.” We now know that some of these families have a higher risk for this cancer because they have an inherited defect in certain genes that normally help repair damage to DNA. If these repair enzymes aren’t working properly, damage to DNA is more likely to persist and cause cancer.
DNA repair defects like this have also been found in endometrial cancer cells from women who haven’t inherited them.
One of the normal genes responsible for suppressing tumor growth, called PTEN, is often abnormal in endometrial cancers. And we know that endometrial cancers without other tumor suppressor genes (or with inactive ones), like the KRAS and the TP53 gene, tend to be more likely to come back after initial treatment.
Source: “What’s New in Endometrial Cancer Research?” (American Cancer Society)
Women born with mutations in the genes linked to endometrial cancer not only have a high lifetime risk, but they’re also more likely to develop the cancer at a young age. The genes linked to endometrial cancer risk include:
Source: “Endometrial Cancer” on the FORCE (Facing our risk of cancer EMPOWERED) website
Find more about these genes, their risks, and guidelines for screening, preventing and treating cancers in people with inherited mutations in these genes:
Genes linked to Endometrial Cancer Risk
Lung
inherited mutations alone are not thought to cause very many lung cancers.
Still, genes do seem to play a role in some families with a history of lung cancer. For example, people who inherit certain DNA changes in a particular chromosome (chromosome 6) are more likely to develop lung cancer, even if they don’t smoke or only smoke a little.
Some people seem to inherit a reduced ability to break down or get rid of certain types of cancer-causing chemicals in the body, such as those found in tobacco smoke. This could put them at higher risk for lung cancer.
Other people inherit faulty DNA repair mechanisms that make it more likely they will end up with DNA changes. People with DNA repair enzymes that don’t work normally might be especially vulnerable to cancer-causing chemicals and radiation.
Some non-small cell lung cancers (NSCLCs) make too much EGFR protein (which comes from an abnormal EGFR gene). This specific gene change is seen more often with adenocarcinoma of the lung in young, non-smoking, Asian women, but the excess EGFR protein has also been seen in more than 60% of metastatic NSCLCs.
Lung Cancer Causes | Lung Cancer in Non-Smokers
*******************************
Certain inherited mutations increase an individual’s risk of developing small cell lung cancer, an aggressive form of lung cancer, according to a new study from CCR scientists. However, patients with the disease who harbor these mutations may be more likely than others to respond to therapies that exploit defects in DNA repair pathways; they also appear to have a better prognosis when treated with a standard chemotherapy regimen.
https://ccr.cancer.gov/news/article/genetics-not-just-smoking-influence-small-cell-lung-cancer-risk
But inherited mutations alone are not thought to cause very many lung cancers.
Still, genes do seem to play a role in some families with a history of lung cancer. For example, people who inherit certain DNA changes in a particular chromosome (chromosome 6) are more likely to develop lung cancer, even if they don’t smoke or only smoke a little.
Some people seem to inherit a reduced ability to break down or get rid of certain types of cancer-causing chemicals in the body, such as those found in tobacco smoke. This could put them at higher risk for lung cancer.
Other people inherit faulty DNA repair mechanisms that make it more likely they will end up with DNA changes. People with DNA repair enzymes that don’t work normally might be especially vulnerable to cancer-causing chemicals and radiation.
Some non-small cell lung cancers (NSCLCs) make too much EGFR protein (which comes from an abnormal EGFR gene). This specific gene change is seen more often with adenocarcinoma of the lung in young, non-smoking, Asian women, but the excess EGFR protein has also been seen in more than 60% of metastatic NSCLCs.
Gene changes related to lung cancer are usually acquired during a person’s lifetime rather than inherited. Acquired mutations in lung cells often result from exposure to factors in the environment, such as cancer-causing chemicals in tobacco smoke
https://www.cancer.org/cancer/lung-cancer/causes-risks-prevention/what-causes.html
Prostate
A small percentage of prostate cancers are hereditary and occur in families. These hereditary cancers are associated with inherited gene variants. Hereditary prostate cancers tend to develop earlier in life than non-inherited (sporadic) cases.
Prostate cancer: MedlinePlus Genetics
************************
Hereditary prostate cancer (HPCa) has the highest heritability of any major cancer in men. The proportion of PCa attributable to hereditary factors has been estimated in the range of 5-15%.
Hereditary Prostate Cancer: Genes Related, Target Therapy and Prevention – PubMed (nih.gov)
*************************
Men with a BRCA1 mutation have a slightly higher risk of prostate cancer. Men with a BRCA2 mutation are 7 times more likely than men without the mutation to develop prostate cancer.
Genetics (breastcancer.org)
****************************
Several inherited gene changes (mutations) seem to raise prostate cancer risk, but they probably account for only a small percentage of cases overall. For example:
Inherited mutations of the BRCA1 or BRCA2 genes, which are linked to an increased risk of breast and ovarian cancers in some families, can also increase prostate cancer risk in men (especially mutations in BRCA2).
Men with Lynch syndrome (also known as hereditary non-polyposis colorectal cancer, or HNPCC), a condition caused by inherited gene changes, have an increased risk for a number of cancers, including prostate cancer.
Other inherited gene changes can also raise a man’s risk of prostate cancer.
https://www.cancer.org/cancer/prostate-cancer/causes-risks-prevention/risk-factors.html
Several inherited mutated genes have been linked to hereditary prostate cancer, including:
BRCA1 and BRCA2: These tumor suppressor genes normally help repair mistakes in a cell’s DNA (or cause the cell to die if the mistake can’t be fixed). Inherited mutations in these genes more commonly cause breast and ovarian cancer in women. But changes in these genes (especially BRCA2) also account for a small number of prostate cancers.
CHEK2, ATM, PALB2, and RAD51D: Mutations in these other DNA repair genes might also be responsible for some hereditary prostate cancers.
DNA mismatch repair genes (such as MSH2, MSH6, MLH1, and PMS2): These genes normally help fix mistakes (mismatches) in DNA that can be made when a cell is preparing to divide into 2 new cells. (Cells must make a new copy of their DNA each time they divide.) Men with inherited mutations in one of these genes have a condition known as Lynch syndrome (also known as hereditary non-polyposis colorectal cancer, or HNPCC), and are at increased risk of colorectal, prostate, and some other cancers.
RNASEL (formerly HPC1): The normal function of this tumor suppressor gene is to help cells die when something goes wrong inside them. Inherited mutations in this gene might let abnormal cells live longer than they should, which can lead to an increased risk of prostate cancer.
HOXB13: This gene is important in the development of the prostate gland. Mutations in this gene have been linked to early-onset prostate cancer (prostate cancer diagnosed at a young age) that runs in some families. Fortunately, this mutation is rare.
Other inherited gene mutations may account for some hereditary prostate cancers, and research is being done to find these genes.
https://www.cancer.org/cancer/prostate-cancer/causes-risks-prevention/what-causes.html