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Cancer and Genetics

It is known that cancer is widely discussed in the world and while much research has

been done, what is truly known about its etiology? Cancer affects millions of people in the

United States and often can be found in multiple people in families. One can ask anyone in the

United States and most know someone who has or has had cancer in their lifetime. I have a

personal connection to cancer through many people in my family, but one important one is my

dad. He had colon cancer at an age younger than most people who have it are, and it was a

slightly advanced stage when discovered. This raises the question of the connection between

cancer and genetics for me because could mean a higher possibility of getting cancer for me?

Statistically speaking, it is estimated that there are 1,806,950 new cases and 606,520

deaths due to cancer in the United States. That means there would be nearly 5,000 new cases

daily, along with almost 1700 deaths. This is clearly a high number, but this paper will focus on

specifically three types: breast cancer, colorectal cancer, and stomach cancer. Breast cancer is

projected to be the leading type of new cases and fourth in deaths. Colorectal cancer is estimated

to be fourth in new cases, but second in deaths, while stomach cancer is estimated to be sixteenth

in new cases and death (American Cancer).

To be able to fully understand the topics of this paper, there are some words that need to

be clearly defined. Cancer is a disease where cells grow out of control, mostly due to a mutation,

which is an abnormal change in a gene. Genes are the actual things that transfer the traits from

parent to child and genetics is how those traits are passed down from parent to child through

these genes. These mutations in the genes can be inherited, formed with the child, or acquired,

where the mutation is gained through the environment or lifestyle. For the purpose of this paper,

the focus will be on inherited mutations and the connection with hereditary cancer, which is
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when cancer can occur due to these inherited mutations. When the term “first degree relative” is

used, it is referring to parents, children, or siblings.

There are many myths surrounding cancer that need to be addressed before hereditary

cancer can be fully discussed. While this type of cancer is passed down through a family, it is not

contagious. No cancers can simply be contracted from another person, unless it is cervical

cancer, which relates to HIV or liver cancer, which relates to Hepatitis B and C. Also, injuries to

certain areas of a body does not mean cancer will appear. Mostly, cancer appears due to an

accumulation of gene mutations, whether it is inherited or acquired (Biswas).

To begin the talks about hereditary cancer, it is important to understand that most cancer

are acquired through the environment or lifestyle, such as skin cancer due to the sun or lung

cancer due to smoking. Only between 5 and 10% of all cancers are caused strictly by inherited

gene mutations (ACS-Understanding). With that being said, it is important to note that many

common cancers are found to be in that small percentage of hereditary cancers. Breast cancer

and colorectal cancer are major types that have been repeatedly connected to inherited genes.

Though less common, stomach cancer has also been connected many times.

So, what cancers are hereditary? It is important to keep in mind that while many cancers

have been found to be connected to inherited gene mutations, that does not mean all cases have

that connection. According to the Canadian Cancer Society’s list, there are 26 cases that have

been considered hereditary at some point. These cancers include bone, kidney, pancreatic,

testicular, thyroid and some leukemia; along with 20 other types. Some cancers found to be

hereditary share the same gene mutations. Later in this paper, it will be discussed what the major

types shown in this paper (the breast, colorectal and gastric cancer) genes all share in common

and how they all relate to other types of cancers.

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The study of how these inherited gene mutations has come a long way in the short time of

its existence. Described as a pioneering event, the discovery of RB1, the gene for a rare pediatric

tumor called retinoblastoma, gave a new tool to families to manage this illness. Another

important discovery is the suppressor gene p53, which is the severe multiorgan tumor gene

known as Li Fraumeni Syndrome. The first genes for HNPCC, which is a form of colorectal

cancer, was discovered in 1993-1994. A long-awaited discovery was the breast cancer genes,

BRCA1 and BRCA2, which will be further discussed later (Sokolenko).

Familial cancer syndrome, another name for hereditary cancer, is where that inherited

mutation is in the tumor suppressor genes, which are meant to keep normal cells under control. If

one mutated gene and one normal gene combine, it often stays normal. If that normal gene

mutates with the already mutated cell, the suppressor genes are stopped, and the cells can freely

grow. There are many characteristics in these cancers that are common. One clear example is

that multiple family members have one type of cancer, or even in some cases, they have different

cancers that can relate back to common mutations. The risk increases when the cancer happens at

a young age or multigenerational. More than one sibling with cancer and more than one type of

cancer in one family member also increases the risk. If the type of cancer does not normally

affect the sex of the person that has it, such as breast cancer in men, the risk is also increased. It

is important to remember that the chance of transferring the gene lowers with the distance in

relation. This is the reason why first-degree relatives with cancer play such a major role in

hereditary cancers (ACS – Family).

Measuring the risk of hereditary cancer is still being researched, but there is information

available now that many use. The presence of hereditary cancer syndrome is measured by single

gene analysis, multigene panels, and whole exam sequencing, as well as looking for recurrent
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mutations. In cancer patients, the risk of a second cancer is also assessed. In otherwise healthy

people with no known mutation, the goal is to identify those that are at risk for these mutations to

develop (Sokolenko).

Breast cancer is an incredibly common cancer found today in women, but also men in

rare instances. The gene PALB2 is found on chromosome 16 and increases the risk for breast

cancer (Hereditary Cancer). The more common genes related to breast cancer are BRCA1 and

BRCA2, which was briefly discussed earlier. While both increase the risk for breast cancer by

60-90%, BRCA1 is the more common mutation. BRCA2 is rarer because it is related to breast

cancer in men than BRCA1. While the main effect this mutation has is on breast cancer, it also

can increase the risk for ovarian cancer by up to 60% (Sokolenko). Many women’s cancers are

affected by hereditary syndromes including breast, uterus, ovarian, cervix and vulva. BRCA1

also increases the risk for prostate cancer and cholangiocarcinoma, or bile duct cancer (BRCA1).

One example of breast cancer in the familiar cancer syndrome category is HBOC, which

stands for hereditary breast and ovarian cancer, syndrome. These characteristics for a higher risk

of cancer appear when the person with cancer is diagnosed younger than the usual age or when

both cancers show on both sides of the family. If a first-degree relative has this mutation, the risk

for getting the mutation increases by 50% (ACS – Family). For those under 45 years old, the risk

continues to increase if any close relatives had breast or ovarian cancer before that age,

particularly if that person is a male or when more than one relative is diagnosed before then. It

should also be noted that family heritage could have effect on gene mutations because many with

this gene mutation are also of Ashkenazi-Jewish descent (Risk Factors).

Another common type of cancer that has been discovered to have hereditary links is

colorectal cancer, though less than 5% of the cases are found to be familial (Potter). This cancer
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is one of the most common types, especially in Western populations. Multiple gene mutations

have been linked to colon cancer including MLHL, DMS2, MSH2 and MSH6 (Pomerantz).

Others than have been linked are PMS2 and EPCAM, though all of these are also connected to a

few others types of cancers including kidney cancer and liver cancer.

An example of colorectal cancer that has hereditary gene mutations is HNPCC, which

stands for hereditary non-polyposis colorectal cancer. Most of the people than fall under this

category are diagnosed before the age of 50. HNPCC relates to mismatch repair genes,

abbreviated as MMR genes, which repair damages in the body. Often in these cases, those

affected have specifically a first-degree relative that were diagnosed before 50. Also, there were

many that were multi-generational and appeared to be a family trait passed down continuously

(ACS – Family). As for patients that were diagnosed with colorectal cancer before age 35,

around 19% had no history in their family of this cancer. In one study, there were 193 patients

that were able to be evaluated. Of this, 23 people had Lynch Syndrome, 22 have a form of Lynch

syndrome that is mutation-negative, 16 had familial polyposis, two had MMR deficiency and one

had Li-Fraumeni syndrome (Mork). It is estimated that 1 in 279 people in the United States have

a gene mutation for HNPCC, but not all will cause cancer to appear. Lynch syndrome is called

an “autosomal dominant pattern” because it only takes a single inherited gene of it to increase the

risk (Lynch Syndrome).

Colorectal cancer has a personal connection to my life, as I mentioned earlier. Now that

the hereditary connections to this type have been explained, I feel that I have a better

understanding of my possibility for developing this through genes. Since less than 5% of cases

are actually related back to hereditary genes, it is more likely that this case is not hereditary than

it is, but the possibility is still there. In terms of HNPCC, my personal case does meet many of
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the characteristics featured. My dad was diagnosed before he was 50 and, since he is my parent,

he is a first-degree relative.

The last cancer related to hereditary genes that this paper will investigate is stomach

cancer, also known as gastric cancer. This type is different than the others because it is not as

solid on what genes are involved. Though, it is common for a first-degree relative to be a

consistent risk factor for this cancer. In a study in Turkey from 2000 and 2003, 14% (168 out of

240) of those with gastric cancer had siblings with it and 12% (148 out of 240) had parents with

gastric cancer (Yaghoobi).

Hereditary diffuse gastric cancer, HDGC, accounts for 1-3% of stomach cancers. A

diffuse is where the entire area is affected instead of smaller areas. The struggle with this specific

type of gastric cancer is that it is not visible on an upper endoscopy as many other gastric issues

are and thus, it is often diagnosed at a late stage. HDGC gives an 80% risk for this cancer to

develop, which is one of the highest risk percentages discussed. Anywhere from 25-40% of

people with HDGC will also have the CDH1 gene mutation. In patients with this gene, they are

born with it and it causes a disfunction in the protein structure of the gene. In cases where there

are two copies of this gene mutation, it becomes a true tumor suppressor. This cancer is also one

where the gene identification is hard to work with because up to 75% of those with HDGC do

not have this gene and it’s cause is unknown (Hereditary Diffuse).

HBOC, HNPCC, and HDGC all create pre-dispositions to their respective cancers, as

well as some others for each. HBOC increases the risk for breast cancer and ovarian cancer as

mentioned, but also includes small chances of pancreatic, prostate and melanoma; though the last

one is only with the BRCA2 gene. For HNPCC, there are many others types of cancer aside from

colorectal that are increased with this disorder. Gastric, small intestine, liver, urinary tract, brain
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and skin cancer risks are all increased, along with ovarian and endometrial cancer in women with

it. HDGC can also increase the risk for a certain type of breast cancer, prostate cancer and

colorectal cancer. As it can be seen, while certain mutations are mainly connected to one type of

cancer, they can also be shown to increase the risk of other cancers by smaller chances.

The short film Genetic Detectives has a slightly different view that many other sources

discussed in the paper. According to this video, it is rare to be sick just due to a gene. Instead, it

comes from behavior, environment, and the gene’s interaction in the body. The gene only makes

the body vulnerable to certain illness. It also says that the environment plays a role in training the

body and immune system, which makes some humans more vulnerable to these certain diseases

while others are practically immune to it. While this source has a different view on the topic, I

feel that it is important to include because it helps show that so much more research needs to be

done to truly see how genes play a role in illness and how they can be passed down.

Researchers have found many relationships between genes and cancers, but there is still

refutable information that can be found on the topic. It is hard to say for sure, but in cases of

breast cancer, colorectal cancer, and gastric cancer, genes can be easily connected to hereditary

cases. As I stated in the beginning, my dad had colorectal cancer years ago. Since it is found that

colorectal cancer has hereditary connections, this subject is rather important to me because it

could have an impact on my personal health and life. It is clear that more research needs to be

done, not only for the cancers discussed here, but for all cancers that could be eventually be

linked through genetics.

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Works Cited

ACS Medical Content and News Staff. “Family Cancer Syndromes.” American Cancer Society,

4 Jan. 2018, www.cancer.org/cancer/cancer-causes/genetics/family-cancer-

syndromes.html.

ACS Medical Content and News Staff. “Understanding Genetic Testing for Cancer.” American

Cancer Society, 10 Apr. 2017, www.cancer.org/cancer/cancer-

causes/genetics/understanding-genetic-testing-for-cancer.html.

“American Cancer Society: Cancer Facts & Statistics.” American Cancer Society | Cancer Facts

& Statistics, cancerstatisticscenter.cancer.org/#!/.

Biswas, Jaydip. “Debunk the myths: oncologic misconceptions.” The Indian journal of medical

research vol. 139,2 (2014): 185-7.

“BRCA1 Gene - Genetics Home Reference - NIH.” U.S. National Library of Medicine, National

Institutes of Health, ghr.nlm.nih.gov/gene/BRCA1.

“Genetic Detectives.” Films Media Group, 2002, digital.films.com/PortalPlaylists.aspx?

wID=19259&xtid=43855. Accessed 18 May 2020.

“Hereditary Cancer.” Causes of Cancer – Genetic Mutations | BRCA & HBOC Mutations, 20

Feb. 2017, www.facingourrisk.org/understanding-brca-and-hboc/information/hereditary-

cancer/hereditary-genetics/?subcat_nice_name=hereditary-genetics&tab_type=index.

“Hereditary Diffuse Gastric Cancer - Genetics Home Reference - NIH.” U.S. National Library of

Medicine, National Institutes of Health, ghr.nlm.nih.gov/condition/hereditary-diffuse-

gastric-cancer.
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“Lynch Syndrome - Genetics Home Reference - NIH.” U.S. National Library of Medicine,

National Institutes of Health, 9 June 2020, ghr.nlm.nih.gov/condition/lynch-syndrome#.

Mork, Maureen E et al. “High Prevalence of Hereditary Cancer Syndromes in Adolescents and

Young Adults With Colorectal Cancer.” Journal of clinical oncology : official journal of

the American Society of Clinical Oncology vol. 33,31 (2015): 3544-9.

doi:10.1200/JCO.2015.61.4503

Pomerantz, Mark M, and Matthew L Freedman. “The genetics of cancer risk.” Cancer journal

(Sudbury, Mass.) vol. 17,6 (2011): 416-22. doi:10.1097/PPO.0b013e31823e5387

Potter, John D., and Noralane M. Lindor. Genetics of Colorectal Cancer. Springer New York,

2009.

“Risk Factors for Breast Cancer at a Young Age.” Centers for Disease Control and Prevention,

Centers for Disease Control and Prevention, 5 Apr. 2019,

www.cdc.gov/cancer/breast/young_women/bringyourbrave/breast_cancer_young_women

/risk_factors.htm?s_cid=byb_sem_009.

Sokolenko, Anna P, and Evgeny N Imyanitov. “Molecular Diagnostics in Clinical

Oncology.” Frontiers in molecular biosciences vol. 5 76. 27 Aug. 2018,

doi:10.3389/fmolb.2018.00076

“Which Cancers Are Hereditary? - Canadian Cancer Society.” Www.cancer.ca,

www.cancer.ca/en/prevention-and-screening/reduce-cancer-risk/make-informed-

decisions/check-family-history/which-cancers-are-hereditary/?region=on.
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Yaghoobi, M., et al. “Family History and the Risk of Gastric Cancer.” British Journal of Cancer,

vol. 102, no. 2, Jan. 2010, pp. 237–242. EBSCOhost, doi:10.1038/sj.bjc.6605380.