Inherited Forms of Cancer: Review of Genetic Syndromes and Cancers

This report provides a comprehensive review of inherited forms of cancer, exploring the genetic predispositions and syndromes that contribute to cancer development. It discusses several key syndromes, including Li-Fraumeni syndrome, which is linked to mutations in the TP53 gene, increasing the risk of various cancers, and Lynch syndrome, associated with defects in MMR repair genes and early-onset colorectal cancer. The report also examines the roles of BRCA1 and BRCA2 genes in breast and ovarian cancer susceptibility, as well as the impact of genetic mutations on renal cell carcinoma and other cancer types. The review highlights the importance of genetic testing, family history, and environmental factors in understanding and managing the risks associated with inherited cancers, concluding that genetic predisposition plays a critical role in elevating cancer risk in carriers compared to the normal population.

Running head: INHERITED FORMS OF CANCER
Inherited forms of cancer
Name of the Student
Name of the University
Author Note

1INHERITED FORMS OF CANCER
There are various forms of cancer that run in families and are inherited from one
generation to other. This is because, abnormal genes responsible for cancer can be passed
through germ line transmission and accounts for 5-10% of cancer. Mostly inherited mutations
occur in tumor suppressor genes causing family cancer syndromes. This syndrome include
the colon cancer, breast and ovarian cancer, leukemia and sarcoma (Cancer.org, 2020). The
purpose of this review is to dicuss about inherited forms of cancer.
Li-Fraumeni syndrome is triggered by a mutation in TP53 gene that is carried through
germline, this gene encodes for a tumor suppression gene P53 and regulates cell cycle. Due to
this type of inherited mutation, cancer can develop in multiple oragan systems seen specially
in younger age. It is observed that mutation carried by 50% of the population have the
probability of developing cancer before 30 years of age along with a risk in women and men
accounting to 100% and 70% respectively. These type of mutation can occur due to the
interaction between gene and environment such as radiation effect can lead to defect in the
DNA repair mechanism of these genes in mutated TP53 genes (McBride et al., 2014). Most
cancer types are associated with mutation in tumor suppressor genes. It has been found in
many studies that most common types of inherited cancer are colon and breast cancer.
However renal cell carcinoma accounts for 5-8% of kidney cancers occurring in population
reaching 75 years of age in United States. There are suggestions that 60% of patients
suffering from renal cell carcinoma have inherited form of cancer. Upon genetic testing, it
was revealed that a family history if this kidney cancer was associated with clinical
manifestations including cerebellar hemangioblastoma, leiomyomas and cutaneous
fibrofolliculomas (Shuch et al., 2014) . Patients develop renal carcinoma by an early age that
is 46 years or younger. Most of the inherited renal carcinoma syndromes are classified as
autosomal dominant inheritance. This type of cancer is manifested by various syndromes
which are useful for detection and screening of the hereditary forms in patients at an early
stage.
All cases of colorectal cancer are associated with hereditary factors and the inherited
froms are classified as polyposis syndrome and nonpolyposis syndrome. In 5-15% of cases
hereditary factors contribute to colorectal cancer. Polyposis can be further classified into
APC, MUTYH, POLE and POLD1. APC polyposis occurs due to a mutation in the APC gene
which leads to a transcriptional activation of many genes and oncogenes, and this form is a
genetic autosomal dominant syndrome. It is characterized by several colorectal adenomas at
middle and second last stage of life. MUTYH polyposis is caused by mutation of MUTYH

2INHERITED FORMS OF CANCER
gene responsible for DNA repair and is inherited as recessive syndrome where people having
this form of polyposis will have a risk of 60-70% in developing colorectal cancer. POLD1
and POLE have germline mutations with multiple adenomas and colorectal cancer at an early
stage. Lynch syndrome is a form of nonpolyposis colorectal cancer that is caused by
inheritance of defected MMR repair genes through autosomal dominant inheritance and is
manifested as early onset of colorectal cancer. The mutation of MMR genes further cause
mutation in tumor suppressor genes and activation of oncogenes leading to accelerated
carcinogenesis.
Mutation in two genes are responsible for causing breast cancer that include BRCA1
and BRCA2 that are known as breast cancer suceptibilty genes. However these gentic
muations can also lead to cancer in multiple organs such as ovary. Mutations in these genes
are accountable for a life-time risk of developing breast and ovarian cancer that can be
inherited. Along with this any changes in the expression of these genes can cause breast
cancer with sporadic forms as these genes are responsible for DNA repair and regulation of
DNA damage and act as tumor suppressor genes. Alongside breast and ovarian cancer due to
germline muattions, it can also elevate risk prostate and pancreatic cancer development
(Bunz, 2016). It has been noticed that 30-40% of spoaradic forms of cancer are related to lack
of BRCA1 gene expression. Carriers of this mutation in BRCA1 and BRCA2 pose a life-
time risk of 45-80% in occurrence of breast cancer whereas 45-60% for BRCA1 nad 11-35%
for BRCA2 in developing ovarian cancer. Women revealed an increased risk of 10-15% in
breast and ovarian cancer development after the age of 40 years. However carriers with
BRCA1- mutation develop cancer in the ovary at a young age compared to carriers of
BRCA2 mutation and in case of sporadic cancer (Paul & Paul, 2014).
Therefore it can be concluded from the above review that genetic predisposition plays
a critical role in elevate drisk of cancer in carriers compared to normal population. Families
are found with most common cancer cases such as colorectal, ovarian and breast cancer at a
yound age. Finally syndromes manifested the occurrence of genetic mutations produces high
risk of cancer in carriers (Eeles, 1996).

3INHERITED FORMS OF CANCER
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