Cancer genetics is the study of the contribution of genetics to
an individual’s risk for cancer. Approximately one in three
people will develop cancer in their lifetime. Many factors can influence
a person’s risk for developing cancer, such as:
- Age
- Tobacco use
- Obesity
- Nutrition
- Chemicals
- Radiation
- Infectious organisms
- Genetics
Some of these risk factors
can be modified through lifestyle, but some factors cannot be changed.
Approximately
5-10% of all cancers are caused by inherited gene mutations that predispose
people to develop cancer. These gene mutations can be passed down through
the generations. Knowledge of family history is very important.
Characteristics
of a family history that increase the chances of hereditary cancer are:
- Cancer at an early age,
- The same cancer occurring in many family members,
- Many cancers occurring in
one person, and/or
- Breast or ovarian cancer in the context of Ashkenazi (Eastern
European) Jewish ancestry.
There are genetic tests
available for some cancers that can explain if personal and/or family history
is due to an inherited gene mutation. If a person has a gene mutation
related to cancer predisposition, they are at an increased risk for developing
cancer and should undergo increased cancer surveillance. If a person has
a normal gene test result, their risk for cancer may lessen but they may still
be at an increased risk.
We have more than 20,000
genes and it is possible that the specific gene causing your family history of
cancer has not been discovered. In this case, people with a normal gene
test result may still need to have increased monitoring. It is important
that a board-certified genetics specialist provide a hereditary cancer risk
assessment before genetic testing and interpret the results of the genetic
test.
Statistics - American Cancer Society
Hereditary Breast Cancer
One in eight women (12.5%)
will develop breast cancer in their lifetime. Several genes have been
discovered that when mutated or changed can increase a person’s risk of breast
cancer.
The BRCA1 and BRCA2 genes account for more
than half of hereditary breast cancer. Other genes, including p53, PTEN, CHEK2, ATM, and other
undiscovered genes are also involved in hereditary breast cancer. A gene
mutation can increase a person’s risk for different types of cancers.
While the BRCA genes
are most known for their breast cancer risk, they also increase the risk for:
- Ovarian
- Prostate
- Pancreatic cancer
TP53 gene mutations cause a condition called Li-Fraumeni
Syndrome and are associated with an increased risk of a variety of cancers
including:
- Sarcoma
- Breast
- Brain
- Leukemia
- Adrenal gland cancers
A PTEN gene
mutation causes Cowden Syndrome. It is associated with abnormal skin growths as
well as benign (non-cancerous) and malignant (cancerous) tumors of the:
There are many screening tools available to detect breast cancer
at an early stage. It is recommended that people at increased risk for
breast cancer have mammogram surveillance as well as breast imaging Magnetic
Resonance Imaging (MRI).
Indications for a genetics
evaluation for hereditary breast cancer include:
A personal history of:
- Breast cancer before the age of 50 or ovarian cancer at any age,
- Bilateral breast cancer or two or more primary cancers of the
breast,
- Breast and ovarian cancer in the same individual, and/or
- Breast cancer in a male.
A maternal or paternal
family history of:
- Two or more people in the family with breast and/or ovarian
cancer,
- One or more close male relatives with breast cancer,
- Early onset breast or ovarian cancer (before age 50) in a close
relative, and/or
- Confirmed genetic mutation in a relative.
* People who belong to certain ethnic groups, such as those of
Ashkenazi Jewish descent, are more likely to have a BRCA gene mutation. Some
individuals may be appropriate candidates for genetic testing. This is true
even if they do not have significant personal or family history of breast
and/or ovarian cancer.
Resources
Genetic Testing for Breast and
Ovarian Cancer Risk
Genetics of Breast and Ovarian
Cancer
Local and national support
groups for
Hereditary Breast and Ovarian Cancer.
Hereditary Colon Cancer
The lifetime risk for developing colorectal cancer is about 1 in
19 (5.4%). Many factors can
increase a person’s risk for developing colon cancer and can include:
- Age
- Diet
- Obesity
- Physical inactivity
- Smoking
- Alcohol
- History of Ulcerative Colitis or Crohn’s disease
- Family history
Approximately 5% of people
with colon cancer have an inherited susceptibility to the disease.
Two genetic conditions
that can increase a person’s risk for colon cancer are Familial Adenomatous
Polyposis (FAP) and Hereditary Non-Polyposis Colon Cancer (HNPCC).
FAP is caused by mutations
in the APC and MYH genes. It causes a
person to develop many, often thousands, of polyps in their colon. A
polyp is a mushroom-like growth in the colon that can be cancerous. If
left untreated a person with FAP has about a 100% chance of developing colon
cancer.
HNPCC is also often called
Lynch syndrome. Lynch syndrome is caused by mutations in several genes,
including MLH1, MSH2, MSH6, and PMS2. Individuals with
Lynch Syndrome do not develop as many polyps as in FAP, but they still have an
increased risk of colon cancer. Lynch syndrome also increases a person’s
risk of uterine, ovarian, stomach, and other cancers.
Colonoscopy is a screening
tool to detect and remove polyps in the colon. People at increased risk
for colon cancer must have colonoscopies more often to screen for colon cancer.
Indications for a Genetic Evaluation
A personal or family history of:
- Colon cancer before the age of 45
- Pre-cancerous polyps before the age of 40
- More than 20 pre-cancerous polyps
- Uterine cancer before the age of 45
- Three or more people in the family with colon, uterine, stomach,
or ovarian cancer
- Confirmed genetic mutation in a relative
- Genetics of Colon Cancer
Von Hippel Lindau Syndrome
Von Hippel Lindau Syndrome (VHL) is a genetic (inherited)
condition. VHL predisposes an individual who has this condition to a variety of
tumors. The most common tumors seen in VHL include:
- Hemangioblastomas of the retina/brain/spine
- Pheochromocytoma tumors of the adrenal gland
- Kidney cancer of the clear cell type
It is important to promptly diagnose VHL. Most tumors associated
with VHL are benign (non-cancerous). Benign tumors can still cause serious
problems. For example, a hemangioblastoma is a benign tumor involving
blood vessels. Retinal hemangioblastomas can cause vision loss and even
blindness. Pheochromocytomas (pheo) are also typically benign but can
cause uncontrollable high blood pressure.
Other tumors include
- Endolymphatic sac tumors
of the inner ear
- Benign kidney and
pancreatic cysts
- Benign tumors of the
reproductive tract
VHL is caused by mutations
in the VHL gene. If a
parent has VHL then each of their children has a 50% chance of also having VHL.
Additional information.
Multiple Endocrine Neoplasia Type 1 (MEN1)
MEN1 is a condition that
causes a person to develop tumors in their endocrine glands. This primarily involves
the parathyroid, pancreas, and pituitary gland, as well as other characteristic
tumors. MEN1 is caused by a mutation in the MEN1 gene.
Parathyroid Tumors
The most common tumors to
develop in MEN1 are those involving the parathyroid glands. Nearly 100% of
people with MEN1 will develop parathyroid tumors in some or all the parathyroid
glands by the age of 50 years. These tumors are typically benign (not
cancerous) and may cause health problems because of the excessive hormones they
produce. Parathyroid tumors produce increased amounts of parathyroid
hormone, causing hyperparathyroidism. Excess parathyroid hormone causes
calcium to leave the bones and go into the blood. Elevated levels of
calcium in the blood are called hypercalcemia.
This can cause:
- Bone weakness (osteoporosis)
- Kidney stone formation
- Fatigue
Pancreatic Tumors
People with MEN1 can also develop tumors in the pancreas.
Pancreatic tumors in MEN1 are named after the hormone they produce. Gastrinoma
and insulinoma tumors are the most common. A gastrinoma produces excess
gastrin and can cause ulcers, reflux, and diarrhea. These symptoms are
called Zollinger-Ellison syndrome (ZES). Gastrinomas can also occur in
the duodenum and can be malignant (cancerous). An insulinoma produces
excess insulin and causes hypoglycemia (low blood sugar). Insulinomas are
almost always benign.
Pituitary Tumors
The pituitary tumors found in MEN1 are also named after the
hormone they produce, with prolactinoma being the most common. A
prolactinoma produces excess prolactin. It can cause menstrual
irregularity in women and reduced libido in men. Pituitary tumors can
cause other symptoms such as headache and changes in vision, by pressing on nearby
structures in the brain. Pituitary tumors in MEN1 are typically
benign.
Other Tumors in MEN1
Less often, people with MEN1 will develop carcinoid or
adrenocortical tumors. Carcinoid tumors occur in the thymus gland or lung
and can be malignant. Adrenocortical tumors occur in the adrenal gland
and are typically benign. Non-endocrine, benign tumors may also develop,
such as facial angiofibromas, collagenomas, and lipomas.
Summary of Cancer Risks in MEN1
In MEN1, the highest risks for cancer are tumors in the
pancreas, duodenum, and carcinoid tumors.
*MEN1 should not be
confused with a condition called MEN2. While MEN1 and MEN2 are similar in
that they both predispose people to develop tumors of the endocrine glands,
they are two completely different conditions.
Multiple Endocrine Neoplasia Type 2 (MEN2) & Medullary
Thyroid Cancer
MEN2 is a condition that causes a person to develop tumors in
their endocrine glands, including the thyroid, parathyroid, and adrenal
glands.
People with MEN2 are at risk of developing a specific type of
thyroid cancer called medullary thyroid cancer. The age of onset varies
and may occur in young children.
In MEN2, the tumors that develop in the adrenal and parathyroid
glands are typically benign (not cancerous) but can cause serious health
problems because of the excessive hormones they produce. Tumors can
develop in the adrenal gland called pheochromocytoma (pheo). These tumors
produce excessive amounts of hormones called catecholamines (such as
adrenaline), which can cause a person to have very high blood pressure.
People with MEN2 can also develop tumors in the parathyroid
glands that produce excessive amounts of parathyroid hormone. This is
called hyperparathyroidism. Excess parathyroid hormone causes calcium to leave
the bones and go into the blood. Elevated levels of calcium in the blood
are called hypercalcemia. This can cause the bones to become weak
(osteoporosis) and kidney stones to develop.
25% of all people
diagnosed with medullary thyroid cancer have the hereditary form caused by
mutations in the RET gene.
Most of these people have a family history of medullary thyroid cancer, but
sometimes they do not.
Types of MEN2
MEN2 is classified into types based on the family history and
the specific RET gene mutation identified: MEN2A and MEN2B. Familial Medullary
Thyroid Cancer (FMTC) is grouped with MEN2 because it is also caused by RET
gene mutations. MEN2A is the most common type of MEN2. There is a very high
risk of medullary thyroid cancer in MEN2A. The typical age of onset is in young
adulthood. About 50% of people with MEN2A will develop a pheochromocytoma and
about 25% will develop hyperparathyroidism.
MEN2B is the most aggressive form of MEN2. It causes medullary
thyroid cancer to develop in early childhood. About 50% of people with MEN2B
will develop a pheochromocytoma. Hyperparathyroidism is uncommon. Individuals
with MEN2B can also develop:
- Benign nodules on their
lips and tongue
- Abnormalities of the
gastrointestinal tract
- Taller stature than
expected in comparison to their family members
FMTC occurs when there is a family history of medullary thyroid
cancer and no other characteristics of MEN2 in the family. The onset of
medullary thyroid cancer is typically in middle age.
*MEN2 should not be confused with a condition called MEN1. While
MEN1 and MEN2 are similar in that they both predispose people to develop tumors
of the endocrine glands, they are two completely different conditions.
Additional
information.
Retinoblastoma
Retinoblastoma is a tumor of the developing retina (part of the
inner eye) that occurs in children. Most of these tumors occur before the
age of five and many are present at birth. Tumors can be unilateral
(present in only one eye) or bilateral (present in both eyes).
Approximately 60% of patients have unilateral retinoblastoma and 40% have
bilateral retinoblastoma.
Retinoblastoma is caused by mutations in the RB1 gene. The mutation
often occurs after birth (usually presents as unilateral in these cases) but is
sometimes hereditary (often presents as bilateral in these cases).
In hereditary retinoblastoma, RB1 gene mutations are either “passed down” from
a parent or occur early in the development of the child. If a parent has
hereditary retinoblastoma then each of their children has a 50% chance of
inheriting the same gene mutation and developing retinoblastoma. If it is
not hereditary, the risk to future generations is quite low.
Besides eye tumors,
children with hereditary retinoblastoma are at increased risk for other types
of cancer or tumors. These include rare tumors of the pineal gland (a gland
found in the brain), and cancers of bone, soft tissue, and skin. Radiation
exposure greatly increases the risk of developing secondary tumors. It is important to identify children at risk
for retinoblastoma and other tumors as early as possible to prevent damage.
Genetic testing of the RB1 gene
is available with about 80% of mutations in the RB1 gene detected. A
negative genetic test result does not rule out hereditary retinoblastoma, as
some mutations are not currently detectable.
Patients with bilateral retinoblastoma are assumed to have the hereditary
form of this condition, although finding the specific mutation is not always
possible. 10-17% of patients with unilateral retinoblastoma also have the
hereditary form. If a mutation is identified in a person, it is important
to determine if other family members are at risk.
Early testing and recognition of people at high risk for
retinoblastoma may allow for timely intervention and improved outcomes.
Using a variety of current treatments, preservation of sight in retinoblastoma
patients is now possible.
Additional
information.