Impact of BRCA Mutations on Cancer Prognosis

This assignment delves into the impact of BRCA mutations on cancer prognosis, specifically focusing on breast cancer. It provides a systematic review and meta-analysis of studies examining the relationship between BRCA mutations and metastatic relapse, as well as cause-specific survival after radical treatment for localized prostate cancer. Additionally, it discusses the role of BRCA mutations in ovarian cancer diagnosis, monitoring treatment, and detecting recurrent disease. The assignment also explores the impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation.

Running head: BRCA-1 and BRCA-2 1
BRCA-1 and BRCA-2
Student’s (Name)
Institution

BRCA-1 and BRCA-2 2
QUESTION 1
Introduction
BRCA-1 and BRCA-2 (Breast Cancer 1 and 2) are genes in the human body that produce
tumor suppressor proteins. This gene modulates and control the system of cell division in
ensuring that cell occurrence is neither rapid nor out of control. They also help in the repairing of
damaged DNA to ensure steady cell genetic material. In case of any alterations of these genes
there will be genetic changes that will result in cancer. Some of the cancer that are mostly
associated with BRCA-1 and BRCA-2 are mostly breast cancer, ovarian cancer and other types
of cancer like fallopian tube, peritoneal cancer and prostate cancer among men and pancreatic
cancer for both men and women, an example of. Mostly women are affected by this cancer if
they inherited this problems from their parents (Finch et al., 2014). An example of a mutation for
BRCA-2 is FANCD1 which is inherited form parents and can cause anemia associated with
tumors and leukemia at early stages. (DNA)Deoxyribonucleic acid are nucleotides that carry
genetic instructions used in the genetic growth and development in the living organism. This
essay will understand the role of BRCA-1 and BRCA-2 in DNA repair and the implication of
mutations in these to cancers.
(i) Structure and functions of BRCA-1and BRCA-2
BRCA 2 gene is composed of 27 exons almost twice the size of BRCA1 with
approximately 3418 amino and 384kDAa(Syngal, 2015) .BRCA 1 and BRCA 2 are tumor
suppressor genes that incase of mutation lead to cancerous diseases, some functions of this genes
are :Firstly, They contribute to the repair of DNA genes and regulation of DNA damage in
living organisms, secondly they help in the maintenance of chromosol stability thereby
protecting chromosome from damage and embryo proliferation .Recent studies have shown that

BRCA-1 and BRCA-2 3
BRCA have helped in the regulation of DNA cell cycle and apoptosis. the main role of BRCA 2
is the regulation of the function of RAD 51 in repairing homologous recombination. BRCA 1 is
mutated in three regions N terminal, BRCT domain and exons 11-13. BRCA 1 has undergone
over 1700 mutations with 858 of this mutation being confirmed as deadly ones with the possibly
of causing cancer, it consists of amino acids and zinc ions.
(ii) The roles of BRCA-1 and BRCA-2 in maintaining genetic
integrity by DNA repair
Carcinogenesis has been on the rise because of genetic mutation, this has resulted to lack
of genes that are responsible for the maintenance of genome integrity. The damage of DNA has
been attributed to direct damage and recombinational damages. BRCA 2 and BRCA 1 genes
have taken part in the repairing of damaged DNA by association with other proteins in mending
breaks in DNA (Subertilla et al. ,2015),BRCA 1 and 2 activate the repair of double strands
breaks (DBS) thereby leading to the process of homologous recombination (HR ) which thus
links these breaks (Hortobagy et al., 2016),they also help in the formation of hinderances to the
spread of damaged gene so that the damaged genes does not affect other important areas, breaks
that can either be natural or as a result of medical emissions or problems with the environment
changes, however it should be noted that damage repair pathways are necessary for growth and
development of organisms except when the repair is defective from the normal repair, other error
sin the DNA include errors during DNA replication, errors as result of exposure of DA to
chemical activities such as ionization radiation and oxidative stress among the cells (Tung et al.,
2015).BRCA lack also causes abnormalities in the G2 checkpoint ,centrosome duplication and
spindle checkpoint leading to destruction of DNA which bocks cell proliferation inducing

BRCA-1 and BRCA-2 4
apoptosis, unless this tumors is broken unit will result to cancer (Baretta, Mocellin, Goldin,
Olopade & Huo, 2016). The role of BRCA has also been attributed to phosphoryl action event,
however this research has not yet been confirmed (Castro, 2015).
(iii) Examples of common inherited mutation
Research has shown that the effects of alteration or mutation of this genes is rampant in
women that in men thereby leading to cancer associated with mutation of this genes mostly in
women. Inheritance of mutation in BRCA 1 and BRCA 2 occur in a pattern called autosomal
dominance pattern (Haley, 2016).) where the mutated dominant gene is found in one of the
autosomes, which means that if the father has a mutated gene there is fifty percent chance of one
half of the children having cancer. It should also be noted that it is also not proven that only
women can undergo inheritance though a large percentage has been seen in them and not all the
people who have inherited this gene are guaranteed to have cancer (Suberbielle et al., 2015). The
effect of this inheritance has been different with some people contracting other diseases like
leukemia while other contract disease like cancer. An example of a serious inheritance mutation
is Fanconi anemia which is inherited from parents it is associated with tumors during childhood
and leukemia.
(iv) Effects of mutation
The sequence of a DNA can be changed in several ways and all this mutations have a
number of effect on the health of the organism in which they occur in, even as more studies are
being taken it has been noted that BRCA1 and 2 can alter in more than 500 ways within which

BRCA-1 and BRCA-2 5
some implications are not known, according to statistics at the age of 70 years there is 60% risk
of those with BRCA mutations having breast cancer which causes sexual dysfunctions (Barretta
et al., 2016),lack or poor of sleep and hormonal (menopausal) imbalance while statistics show
that occurrence of ovarian cancer whether it is inherited or from gene modification that is
developed after birth is at 49% specifically for the ladies (Tung et al., 2015). It has also been
indicated that with gene mutation there are several other diseases and cancers that will develop
from this deficiency such as anemia and leukemia, some scholars have also proven the
relationship between this mutations with tumor suggesting that this mutations could result to
tumor in the organism affected (Hortobagyi et al., 2016). Mostly the effect of mutation is
alteration OF DNA resulting to cancer specifically of the breast and ovary for women and
prostrate for men (Castro, Goh, Leongamornlert, Saunders, Tymrakiewicz, Dadaev & Bancroft,
2015).
(v) Molecular test to diagnose common mutation
There are several ways of testing and recognizing the presence of BRCA
mutation .BRCA2 is twice greater than BRCA1 containing 27 exons and approximately 3418
amino acids and with this property there are methods that can be used in the detection of
mutation in only BRCA 1 or 2 (Hortobagyi et al., 2016). Multigene or panel testing is used in
testing for the mutation in the genes that is attributed to BRCA 1 or BRCA 2 most those that are
associated with breast and ovarian cancer (Fiche et al. 2014). The sample that is used in this
testing is mostly DNA from saliva or blood (Syngal et al., 2015). There are also reference tools
that are used in the process of screening breasts for cancer which is associated with cancer

BRCA-1 and BRCA-2 6
example the use of MRI (Magnetic Resonance Imaging) in carrying out annual breast
examinations.
(vi) Benefits of genetic testing
Genetic testing has proven to be helpful regardless of the outcome of the result whether
positive or negative as explained by gene mutation (Field & Goff, 2018). When the result is
positive indicating gene mutation the affected person will seek medical attention in attempts to
print further spread of cancer and also for provision of tests (Takaoka & Miki, 2018). When the
results are negative of gene mutation a person can freely stop bothering about their gene
mutation and also in avoiding unnecessary checkups and screenings. In the young new born it
will help with prior planning on how to deal with the issue even as the person will grow old to
face diseases because of cancer (Haley, 2016).
Conclusion
In conclusion, it can be noted that there is a significant role of BRCA1 and BRCA 2 in
the repair of DNA. Absence of BRCA1 and BRCA leads to cancer. There is need for carrying
out genetic tests since regardless of the results and some common examples of mutations a result
of this mutation is cancer, leukemia and anemia.

BRCA-1 and BRCA-2 7
Reference
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mutations on breast cancer prognosis: a systematic review and meta-
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Castro, E., Goh, C., Leongamornlert, D., Saunders, E., Tymrakiewicz, M., Dadaev, T., ... &
Bancroft, E. (2015). Effect of BRCA mutations on metastatic relapse and cause-specific
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Field, C., & Goff, B. A. (2018). Dermatomyositis-key to diagnosing ovarian cancer, monitoring
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