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Breast cancer is one of the most common types of cancer affecting women. According to the World Health Organization (WHO), 2.3 million women were diagnosed with breast cancer, and 685,000 lost their lives globally in 2020. 

As of 2020, 7.8 million women have been diagnosed with breast cancer and are alive in the last five years.

Breast cancer survivors are at risk for different health conditions - fatigue, mental health issues, and breast cancer recurrence - to name a few. They must also be aware of the higher risk they carry for developing a second non-breast cancer. 

People who have had breast cancer in the past are at higher risk for developing  other types of cancers, including:

A 2006 study collected data from 13 different cancer registries in places like Singapore, Canada, Australia, and Europe. The study analyzed the data of 525,527 women and followed them for 10+ years.

According to the study, when compared to women who did not have a history of breast cancer, women with past or present breast cancer had:

Another study analyzed the risk of Secondary Non Breast Cancers (SNBCs) in 58,068 Dutch women diagnosed with breast cancer between 1989 and 2003. According to the study, women who had breast cancer in the past had a small but significant risk for developing esophageal cancer, stomach cancer, colon cancer, rectum cancer, uterus cancer, ovarian cancer, soft tissue sarcoma, acute myeloid leukemia (AML), and non-Hodgkin’s lymphoma.

Genetic Factors Influencing Risk For Breast And Other Cancer

The BRCA1 Gene 

The BRCA1 gene (BRCA1, DNA repair associated gene) produces a tumor suppressor protein. This protein is considered beneficial as it hinders uncontrolled cell division, thereby lowering cancer risk. 

Abnormal changes (or variations) in this gene can lead to low or no production of the tumor suppressor protein and increase one’s risk for developing cancers. 

A study reported that  BRCA1 variations lead to breast and ovarian cancers and also increase the risk of other cancers like colon cancer (11.1%), pancreatic cancer (3.6%), and gastric cancer (5.5%).

The BRIP1 Gene 

The BRIP1 gene (BRCA1 interacting protein C-terminal helicase 1) contains instructions for producing a protein that repairs double-strand breaks in DNA. 

Abnormal changes in this gene result in lower production of this protein, which increases the risk of many types of cancers. Cancers associated with variations in this gene are:

The PALB2 Gene 

The PALB2 gene (Partner And Localizer Of BRCA2 gene) contains instructions for producing a protein that works with the BRCA2 protein to repair damaged DNA and suppress tumor growth. Abnormal changes in this gene affect the ability of the BRCA2 gene to prevent tumor cell formation. 

Apart from breast cancer,  this gene is associated with the risk for:

The CHEK2 Gene  

The CHEK2 gene (Checkpoint kinase 2) is also a tumor suppressor gene and produces a kinase enzyme protein called CHK2. 

Abnormal changes in this gene increase the risk of developing breast cancer by two times. It also increases the risk of:

The PTEN Gene  

The PTEN gene produces an enzyme that acts as a tumor suppressor. Almost all tissues in the body have this enzyme in specific quantities. This enzyme prevents the abnormal division of cells by encouraging self-destruction (a process called apoptosis) of these cells. In people with past or present breast cancer diagnoses, variations in this gene can result in an increased risk of:

Non-Genetic factors

Exposure To Radiation

One of the main non-genetic factors that increase a person’s risk of developing other cancers is radiation exposure

There are three basic radiotherapy treatment solutions for breast cancer.

1. Three-dimensional Conformal Radiotherapy (3D-CRT)

2. Intensity-Modulated Radiotherapy (IMRT)

3. Volumetric Modulated Arc Therapy (VMAT)

Many studies report a higher risk of second cancer because of radiation exposure. 

A large study analyzed the risk of second cancers in 46,176 breast cancer survivors. According to the study, one out of 200 women who had received radiation therapy for breast cancer had a higher risk of being diagnosed with other cancers.

Type of Chemotherapy

Chemotherapy is a treatment that uses various drugs to kill abnormally growing tumor cells in the body. It is the most common treatment option for cancer.

Some types of chemo drugs given during breast cancer treatment are associated with an increased risk for developing other types of cancers. 

Chemo agents that are linked with second cancer risks are:

Patients who go through chemotherapy for a longer time or get treated with higher doses of drugs are at a higher risk of developing other cancers. 

Age

While patients who had exposure to radiation therapy and chemotherapy were at higher risk for developing second non-breast cancers, people under the age of 40 who received these treatments were at more risk than the elderly who received treatment.

Smoking

Smoking increases the risk of breast cancer and all other cancers. Smokers diagnosed with breast cancer are at higher risk for developing other cancers in the future when compared to non-smokers.

 A 1994 study tried to find the relationship between smoking, breast cancer, radiation therapy, and the risk of second cancers. According to the study, radiation therapy for breast cancer increased the risk of developing other cancers in smokers and non-smokers. However, in smokers, this risk was much higher.

Recommendations To Bring Down The Risk Of Breast And Other Cancers

Genetic Testing

Genetic testing can be a good aid for treatment planning and risk management if:

Genetic testing will look for specific genes that can increase your risk for breast and other cancers. It will tell you if you are at higher risk for second cancer. In case you belong to the high-risk category, regular screening can help you.

Analyze The Risks In Your Chemotherapy and Radiation Therapy Procedures 

Talk to your doctor about the dosage and type of chemotherapy and radiation treatment you will be receiving for your breast cancer. Some treatments may increase your risk for breast cancer than others.

Adopt Healthy Habits

Some lifestyle changes can lower your risk of developing cancer.

Do Not Fear

The fear of breast cancer recurrence and the fear of developing second cancers can lead to high stress. Stress causes abnormal changes in the cells and can be a cause for cancer recurrence. Fear and stress lead to unwanted behaviors like alcohol abuse, smoking, and excessive eating. All these also increase the risk of developing other cancers. Practicing mindfulness and talking to a mental health expert might help you in controlling stress. 

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Summary

  1. Breast cancer is associated with a higher risk of developing a second non-breast cancer. 
  2. Certain types of cancer like stomach cancer, colon cancer, uterus cancer, ovarian cancer, sarcoma, and Acute Myeloid Leukemia (AML) can develop after a breast cancer diagnosis.
  3. Both genetic and non-genetic influences increase a breast cancer survivor’s risk for developing other types of cancers.
  4. Abnormal changes in genes like the CHEK2, BRCA1, PTEN, ATM, and TP53 can increase the risk of breast and other cancers. 
  5. Non-genetic factors like age, radiation exposure, the intensity of chemotherapy, and lifestyle habits like smoking also increase the risk of developing second non-breast cancers.
  6. A genetic test can tell you if you are at risk for developing a second non-breast cancer after a breast cancer diagnosis.
  7. Following a healthy lifestyle, keeping away fear, and choosing the right radiation and chemotherapy procedures can help bring down the risk of second cancer considerably. 

References

According to a research study by the University of Exeter Medical School in the United Kingdom, men with hemochromatosis, a common genetic disorder due to iron build-up, are ten times more likely to develop liver cancer. 

What is Hemochromatosis?

Hemochromatosis, also called the iron-overload disease, is a condition where too much iron builds up in the body. Usually, the intestines absorb adequate amounts of iron and excrete the rest.

With hemochromatosis, excess iron is absorbed by the intestines, and the body has no way of getting rid of it. As a result, iron gets built up in joints, the pituitary gland, and organs like the liver, heart, and pancreas.

This gradually results in the shutting down of these organs if hemochromatosis is not treated.

Hemochromatosis is more serious in men. Women may be partially protected as they lose some iron during menstruation and childbirth.

Some common symptoms associated with hemochromatosis include:

  1. Joint pain
  2. Weight loss
  3. Fatigue
  4. Low sex drive
  5. Abdominal pain

The HFE Gene

HFE gene is associated with iron homeostasis. A variant (type) of the HFE gene, called the C282Y (the faulty type), is significantly associated with hereditary hemochromatosis.

According to a study published in the American Journal of Human Genetics, the C282Y variant contributes to 26% variation in ferritin levels among monozygotic twins.

Hemochromatosis and Liver Cancer

With hemochromatosis, the iron build-up is commonly seen in the liver. This enlarges the liver and messes up the liver enzymes. It can result in an increased risk of liver conditions like cirrhosis, fibrosis, and cancer. 

Hepatocellular carcinoma (HCC), a primary form of liver cancer, was the first condition in which hepatic iron overload was shown to predispose to the development of HCC.

According to a study, 8-10% of people with hemochromatosis develop HCC.

The Study

The study was led by the University of Exeter Medical School along with the University of Connecticut, Western University in Ontario, and South Warwickshire NHS Foundation Trust.  

This study focused on men and women with two copies of the faulty HFE gene - C282Y. The data of 2890 people aged 40-70 years were analyzed over a nine-year period.

The following were observed:

  1. 21 out of the 1,294 men with faulty genes developed liver cancer
  2. 14 out of these 21 men died of liver cancer
  3. 10 out of these 21 men were not diagnosed with hemochromatosis by the time they developed liver cancer
  4. **More than 7% of the men** with two faulty genes develop liver cancer by 75 years of age
  5. No increase in liver cancer risk was found in women with the faulty genes

The study insists on the importance of early diagnosis of hemochromatosis in order to avoid health complications and even death.

The NHS advises that “it is important to talk to your GP if you have a parent or sibling with hemochromatosis, even if you don’t have symptoms yourself” to identify your risk. 

The lack of impact on women from the faulty HFE gene variant may suggest that periodic blood donations might play a protective role.

Summary

  1. Hemochromatosis is a condition where your body absorbs too much iron resulting in its build-up in joints and organs. It leads to complications like low sex drive, fatigue, and abdominal pain.
  2. When iron builds up in the liver, it can alter the size of the liver and disturb the liver enzymes. Both these factors contribute to the increased susceptibility to liver diseases like fibrosis, cirrhosis, and cancer.
  3. The HFE gene is associated with the regulation of iron levels in the body. The faulty type of the HFE gene called C282Y increases your risk for hemochromatosis. 
  4. A study by the University of Exeter Medical School revealed that men with two copies of the faulty gene are at an increased risk of developing liver cancer. According to the study, by the age of 75, more than 7% of these men had developed liver cancer. No association was found in women with the faulty genes and liver cancer risk.
  5. Genetic testing, which analyzes your HFE gene type, is a key way to prevent and manage hemochromatosis. The NHS advises people who have a sibling or a close family member with hemochromatosis to talk to their healthcare provider for suitable tests.

Reference:

  1. https://www.sciencecodex.com/liver-cancer-ten-times-more-likely-men-common-genetic-disorder-haemochromatosis-661896
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668053/
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995380/
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