Mini Review
A Genetic Approach to Hereditary Cancers
Neslihan Duzkale*
Author Affiliations
Department of Medical Genetic, Diskapi Yildirim Beyazit Training and Research Hospital, Turkey
Received: December 29, 2019 | Published: January 10, 2020
Corresponding author: Neslihan Duzkale, Department of Medical Genetic, Diskapi Yildirim Beyazit Training and Research
Hospital, Turkey
DOI: 10.26717/BJSTR.2020.24.004060
Cancer: It is a disease characterized by the development
of abnormal cells that divide in an uncontrolled manner and
are capable of destroying by spreading to normal tissues. The
main abnormality in cancer development is the continuous and
uncontrolled proliferation of cancer cells. Loss of control in these
cells is the result of the accumulation multiple cell regulatory
system abnormalities. Development of cancer at the cellular level; it
is a multistep process involving the selection and mutation of cells
that proliferate, increase invasion and metastasis capacity. This
change is due to the successive accumulation of changes in genes
that enable the continuation of genetic integrity, cell death, and
control of cellular proliferation [1]. Cancers can occur sporadically
and hereditary in individuals. Sporadic cancers; which is caused
by damaged accumulated in the DNA due to the environment and
aging effect, constitutes approximately 80% of all cancers. This
type of cancer, which is mostly seen in older ages, is unlikely to
have an inherited mutation. Even if there are many cases of cancer
in the family of the individual with cancer, this does not indicate
hereditary transmission. Sporadic cancers can be largely prevented
by lifestyle changes. Hereditary cancers; certain types of cancer
occur in certain genes and are caused by the inherited transmission
of disease-related permanent changes to subsequent generations.
The incidence of these cancers is 5-10% in all cancer cases. They
are seen at an earlier age than sporadic cancers. These cancers may
occur in the individual, in multiple organs and/or at multiple points
of the same organ [2].
Hereditary Cancer Syndromes
Cancer develops due to environmental agents (chemical
carcinogens, radiation, viruses, etc.) and inherited genetic factors
(germline mutations). If an individual has a hereditary cancer
syndrome due to an inherited mutation, there may be an increased
risk of developing certain tumors that may develop relatively
early. In many of the known hereditary malignant syndromes,
the affected genes are usually associated with the repair of DNA
damage or control of the cell cycle. Due to the widespread presence
of malignancies in the population, and because the mutation
screening is laborious and expensive, extreme care must be taken in
the selection of individuals for molecular genetic analysis. Detailed
information of the applicant (proband) for genetic counseling is
learned, at least three generations of family history are questioned,
and pedigree analysis is performed. The history of the prosthetic
and the drawn pedigree analysis usually leads to suspicion of a
defined “hereditary cancer syndrome ve and, if adequate criteria
are met, it is decided to carry out genetic analysis to investigate
relevant gene mutations.
“Increased Risk of Hereditary Cancer Susceptibility ”in
which situations should it think?
If an individual has multiple primary tumor foci in the same
organ, multiple primary tumor foci in different organs or bilateral
primary tumors of the double organs, this may be due to a genetic
basis. Also, if in an individual identifies early diagnosis of cancer,
a rare histological type of cancer cell, rare cancer (breast cancer
in man, etc.), congenital defects and rare diseases with inherited
precursor or cutaneous lesions, hereditary cancer syndrome
should be suspected. Sometimes an individual’s family history
may suggest the presence of hereditary cancer syndrome. For
example; if one of the first-degree relatives has a tumor of the same
or similar type, tumors of the similar region in ≥2 first-degree relatives, ≥2 first-degree relatives, tumors of known hereditary
cancer syndromes, rare tumors in ≥2 first-degree relatives, and ≥2
relatives in two generations in the case of tumors of the region or
etiologically related regions, a genetic cause should be investigated
[3]. Hereditary cancers are inherited by certain genes and are
usually autosomal dominant with incomplete penetrance. There
are several genes that are known today and whose changes can
cause hereditary cancer syndrome and each of the hereditary
cancer syndromes to which these genes are responsible has certain
characteristic tumor spectra (Table 1) [4].
Which genetic tests to select in the family tree and who will
perform genetic analysis should be determined by the Medical
Genetic Specialist. During the genetic counseling, learning in detail
the organs in which the primary tumors of the proband family
reside will facilitate the selection of the responsible gene. For this
reason, a family history of at least 3 generations of proband should
be questioned in detail. Diagnosis and age of cancer patients, risk
factors that may cause diagnosis for each patient in the pedigree
should be questioned. According to the results of genetic testing,
individuals or family members are informed about susceptibility to
certain types of cancer and genetic counseling is provided. When
a disease-related gene variant is detected, in which organ systems
this gene increases the risk of malignancy and the risk increase
rates, the genetic transition pattern of the gene should be explained
in detail with the literature. For all organs that may increase the risk
of malignancy, a multidisciplinary approach to proband is referred
to the relevant departments. In the family of the proband, family
work (co-segregation analysis) is carried out following a certain
algorithm to screen for the disease-related variant of the gene that
is inherited in the genealogy analysis of those likely to be affected.
Most of these syndromes conform to the autosomal dominant
inheritance pattern, i.e. first-degree relatives (mother, father,
children, and siblings) have a 50% risk for this mutation. The
relatives of the patient should be reminded in genetic counseling
that family work tests are susceptibility tests and that only those
who want to learn the risks. Identification of a patient’s cancercausing
mutation provides a reliable predictive diagnosis for
patients’ relatives. This means that when family members at risk
are screened for the presence of the mutation in question, it can be
determined whether they inherit the increased risk of cancer. The
most important objective here is to ensure that family members
with mutations are enrolled in a specific monitoring program
for relevant cancer syndrome. Besides, if the clinical mutation in
a family cannot be detected in the proband, it is not possible to
perform predictive testing on other healthy members of the family.
Family members who do not have a mutation are not included in
the cancer intensive cancer screening and monitoring program.
As a result; many features, such as tumors occurring simultaneously
or at different times in the patient, age at onset of the disease
earlier than expected, and the presence of multiple relatives affected,
indicate the presence of hereditary cancer syndrome. In these
cases, it would be beneficial for the patient and relatives to receive
genetic counseling, if necessary, to perform additional diagnostic
procedures and analyzes, and to receive individual recommendations
for early diagnosis/screening tests. Targeted examinations
can be used to diagnose possible cancer early and, if necessary, to
improve prognosis by removing precursor cancerous lesions. In
summary; defining “hereditary cancer syndrome de in an individual
will enable the individual and his / her family members at risk to
be included in a cancer intensive cancer screening, monitoring, and
prevention program. For this reason, individuals with suspected
hereditary cancer syndrome should consult with a genetics specialist
and get genetic counseling.
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