Over the past decade, scientists have discovered specific inherited factors, or genes, that can contribute to the development of some forms of breast, ovarian, colorectal, prostate and other types of cancer. Hereditary cancer is a cancer that has developed as a result of a gene mutation passed down from a parent to a child.
Genes are present in every cell in our body, contained in structures called chromosomes, which are found in the nucleus of a cell. We have 46 chromosomes that come in 23 pairs. One chromosome in each pair comes from our father, and the other comes from our mother. Each chromosome, in turn, is made up of thousands of genes, which are coded segments of DNA that like chromosomes also come in pairs. A change in the sequence of the DNA that makes up the gene can cause the gene to stop functioning. These genetic changes are called mutations. Inheriting a gene mutation does not necessarily mean that person will develop cancer, but increases their risk factor.
Research and studies have found that certain gene mutations increase the chances of a person to develop certain kinds of cancers, depending on family history. Still, it is important to remember that cancer is not inherited, only the gene that increases the risk factor of developing it.
The Most Common Hereditary Cancers Are:
- Breast Cancer
- Ovarian Cancer
- Prostate Cancer
- Colorectal Cancer
Hereditary Breast and Ovarian Cancer
Breast cancer is the most common cancer of women in the US, affecting about one in eight during their lifetime. Ovarian cancer is less common, affecting about one in 70 women. Breast cancer affects men, but it is uncommon, accounting for less than 1 percent of all breast cancer cases. As a person ages, the chance of getting breast cancer increases.
The most common type of cancer linked to BRCA1 and BRCA2 changes is breast cancer, but mutated forms of BRCA genes are linked to other cancers as well. The BRCA genes, which control cell multiplication and are responsible for repairing cell damage, is a pair which contains DNA from the mother and the father. If the mother or father's BRCA gene is mutated, it may be passed on to a child at conception. In hereditary breast and ovarian cancer, the two diseases are often linked together. This is because they develop from the same mutated genes of BRCA1 and BRCA2.
About 5 to 10 percent of breast cancers are hereditary. In these cases, breast cancer runs in the family. Most breast cancers are not due to inherited changes in genes. Of those that are, about a third are due to mutations in the BRCA1 gene. Another third of breast cancers that run in families are linked to mutations in the BRCA2 gene.
Similarly, 5 to 10 percent of ovarian cancer is hereditary.
Both men and women can pass down a BRCA mutation. All people, whether they have cancer or not, have two copies of both BRCA genes - one from each parent. If you have a parent with a BRCA1 or BRCA2 mutation, you may inherit that parent's mutated BRCA gene, or you may inherit the working BRCA gene. Therefore, you have a 50 percent chance of inheriting either copy of each parent's two BRCA genes. If you inherit a nonworking BRCA gene, you will have an increased risk for cancer. Even though you may inherit a working BRCA copy from the other parent, it takes only one altered BRCA gene to increase risk for breast or ovarian cancer. You also have a 50 percent chance of not inheriting a nonworking BRCA gene from a parent who carries a mutation. If that is the case you have the same risk for cancer as a person in the general population.
By analyzing a blood or saliva sample, a lab can detect DNA changes that indicate a mutation in one of these two genes. If more than one family member is interested in being tested, it is best to start BRCA testing with a person who has (or had) cancer of the breast or ovary. Once a DNA change has been found, that same mutation can be tested for in other family members.
Anyone considering genetic testing should be aware of the possible benefits and risks. There are four possible benefits to testing for BRCA1 and BRCA2 mutations. First, the results may provide a better measure of your cancer risk. Second, the results allow you to tailor cancer screening as needed. Third, the results can guide you in choosing options for cancer-risk reduction, such as surgery. Finally, knowing the test results may benefit others in your family.
While genetic testing poses no physical risk other than that of a blood draw, it may have an emotional impact. This is of special concern if a BRCA1 or BRCA2 change is found and may also have an impact on family members, some of whom may not want to know the results.
Genetics and Colorectal Cancer
Colorectal cancer is the third most common cancer diagnosed among American men and women. About 130,000 new cases of colorectal cancer are diagnosed each year. Six percent of all Americans, one out of every 17, will develop colorectal cancer.
Though most cases occur sporadically, it is estimated that 5 to 10 percent of all colorectal cancers are explained by a specific genetic susceptibility. A person who is diagnosed with colorectal cancer and who has a family history of the disease is more likely to have inherited a cancer gene than a person with no family history of colorectal cancer.
Hereditary Nonpolyposis Colorectal Cancer
Hereditary Nonpolyposis Colorectal Cancer (HNPCC) is also called Lynch syndrome and accounts for approximately 5 percent of all colorectal cancer diagnoses. The syndrome is caused by mutations in specific genes.
Families with HNPCC typically have:
- Three or more closely related family members diagnosed with colorectal cancer.
- Affected family members in two or more generations.
- At least one person with colorectal cancer diagnosed before the age of 50.
The average age of colorectal cancer onset in families with HNPCC mutations is 45 years. Though colorectal cancer is the most common malignancy reported in families with HNPCC, the syndrome is also associated with an increased risk for cancers of the uterus, ovary, stomach, small intestine, biliary system, pancreas, and urinary tract.
There are families that have strong histories of colorectal cancer but in whom HNPCC mutations have not been detected. These families may carry mutations in genes yet to be identified, or there may not be a mutation at all, the cancer history possibly being explained by random chance.
Familial Adenomatous Polyposis
There are other rare forms of hereditary colon cancer. One of these is called Familial Adenomatous Polyposis. In this condition, children develop hundreds or thousands of polyps in the colon at a very early age. These children will almost always go on to develop colon cancer by age 40. There are two other, milder hereditary colorectal syndromes, known as Attenuated Familial Adenomatous Polyposis (AFAP)
and MYH-Associated Polyposis
. Less is known about these two recently discovered syndromes.
By analyzing a blood or saliva sample, a lab can detect DNA changes. However, anyone considering genetic testing should be aware of the possible benefits and risks. Benefits include results that may allow for a more accurate assessment of a person's cancer risk. If the results are positive, doctors can screen earlier, to look for colorectal cancer and other HNPCC-associated cancers. If the results are negative, individuals may not have to screen as aggressively. Also, if a mutation is identified, genetic testing and/or early cancer screening can be offered to other at-risk family members.
There is no physical risk involved in genetic testing, other than that of a routine blood draw, but genetic testing can be emotionally difficult regardless of the results. Also, if a mutation is found, relatives who have not had genetic testing may make assumptions about their own genetic status. Finally, the costs associated with cancer screening and prevention for people with mutations may or may not be covered by their health insurance provider.
Of course, a colonoscopy is considered the best for colon cancer screening. During a colonoscopy, the doctor passes a thin, flexible tube through the anus to look inside the colon. In other settings, doctors may perform sigmoidoscopy, which visualizes only the last third of the colon. Newer tests, such as virtual colonoscopy, that allow imaging of the colon are being developed. If someone in your family has already tested positive for a gene mutation, you may be tested for the specific mutation found in their sample. If you have tested negative for a mutation that's known to run in your family, no further testing is needed.
Genetics and Prostate Cancer
Prostate cancer is the most common type of cancer diagnosed among American men, affecting one in six men during their lifetime. Currently, it is the second leading cause of death due to cancer in men. Fortunately, recent improvements in detection and treatment have significantly improved the outlook for men diagnosed with prostate cancer.
The current recommendation is that all men at average risk should be screened once a year for prostate cancer beginning at age 50. Men who are at an increased risk for prostate cancer should begin screening earlier. African-American men and men with a family history of prostate cancer should begin screening at age 40.
It estimated that 5 to 10 percent of all prostate cancer cases are considered hereditary. However, currently there is no clinical testing for genes involved with prostate cancer. Only recently have studies begun to identify such genes.
At present, many separate genes are thought to be involved: three on chromosome 1, one on chromosome 17, one on chromosome 20, one on chromosome X, and one on chromosome 8, as well as several others. Additional research is needed to determine to what extent these genes are responsible for hereditary prostate cancer. Understanding how these genes are involved is critical for identifying men at increased risk, implementing proper screening procedures, and developing better treatments.
However, men who are concerned about their hereditary risk because multiple family members have developed prostate cancer should discuss their concerns with their doctors and consider making an appointment with a trained genetic specialist.
Genetic counselors discuss your personal and/or family history of cancer. They will simplify complex scientific concepts into terms you can understand. The goal of cancer genetic counseling is to provide clear and clinically relevant information about genetic risk factors in an atmosphere that is supportive and educational.
Genetic counseling is typically recommended for individuals or families with multiple cases of cancer diagnosed at unusually young ages.
Status of Federal Legislation Against Genetic Discrimination
In 2008, Congress passed into law a bill making genetic discrimination illegal. The Genetic Information Nondiscrimination Act of 2008, also referred to as GINA, is a federal law that protects Americans from being treated unfairly because of differences in their DNA that may affect their health. The new law prevents discrimination from health insurers and employers.
The Cancer Genetic Markers of Susceptibility (CGEMS) Project
The Cancer Genetic Markers of Susceptibility (CGEMS)
project began in 2005 as a 3-year pilot study to identify inherited genetic susceptibility to prostate and breast cancer. CGEMS has developed into a robust research program involving genome-wide association studies for a number of cancers to identify common genetic variants that affect a person's risk of developing cancer.
CGEMS relies upon data and case-control studies. Scientists have identified inherited genetic variants associated with cancer risk that may lead to new preventive, diagnostic, and therapeutic interventions. In the future, researchers will apply fine-mapping and deep sequencing techniques to pinpoint the specific variants responsible for disease risk. Ultimately, findings from these studies may yield new preventive, diagnostic, and therapeutic interventions for cancer.
Unlike patients who are carriers of well-recognized genetic mutations like BRCA1 or BRCA2, these women do not have any evidence of genetic alterations that would increase the risk of breast cancer. The increased breast cancer risk in this group of women may be related to a group of genes rather than a single gene mutation. These genetic alterations as a group may have increased predisposition to development of breast cancer.
It is also difficult to separate environmental factors in these patients. The role of environmental factors is difficult to quantify in this situation and how much of this increased risk is caused by common environmental factors is difficult to judge.
Find a Genetic Counselor with help from the National Society of Genetic Counselors.