Iron Loading and Liver Cancer

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Iron Loading and Liver Cancer

• By Andy Donald andrew.donald_at_utoron
  to.ca
• Andrejs Andrijecs a.andrijecs_at_utoront
  o.ca
• Greg Slobodian gregory.slobodian_at_utoronto.ca
• Michelle Neville michelle.neville_at_utoront
  o.ca

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Iron What is it good for?

• Is an essential component of cytochrome proteins
  mediate redox reactions
• Carrier element in hemoglobin, myoglobin
• Free iron can catalyze production of free
  radicals potential of biological toxicity
• Sources
• Animal products, leafy vegetables, tofu, fish,
  chickpeas
• From animal more easily absorbed than from
  vegetables
• Supplements including fumarate, sulfate,
  gluconate

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How it finds its way in..

• Heme or non-heme that is the question
• Ferritin
• Stores Fe
• Transferrin
• Transports Fe everywhere
• Ferroportin
• Gets Fe into the blood

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Hemochromatosis

• Most common form of iron overload disease
• The body absorbs and stores too much iron.
• Excess iron builds up in the organs and damages
  tissues, causing liver, heart and pancreas
  failure.
• Diseased absorb 30 of iron consumed, vs 10 in
  healthy individuals.
• There are two main types, primary and secondary
  hemochromatosis.

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Primary or Hereditary hemochromatosis

• is mainly caused by a defect in a gene called
  HFE (cannot produce HFE protein)
• HFE helps regulate the amount of iron absorbed
  from food.
• C282Y is the most common mutation of this gene
• If C282Y is inherited from both parents the
  individual get hemochromatosis.
• If C282Y is inherited from only one parent, the
  individual is a carrier, however these people may
  still have more than normal iron absorption

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2nd Hemochromatosis (mostly men)

• Iron overload Caused by
• Oral iron pills or iron injections
• Long-term kidney dialysis
• Blood transfusions

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2nd Hemo... Cont...

• Iron overload as a result of blood transfusions
  to correct the following diseases or condition,
  Examples
• Anemia, such as thalassemia and sideroblastic
  anemia
• Atransferrinemia and aceruloplasminemia (both are
  rare, inherited diseases)
• Chronic liver diseases
• (such as hepatitis C, and alcoholismalcoholic
  liver disease)

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FYI - Alcoholism has many motivational factors
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Signs/symptoms that you have to much Iron in your
body
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• Early on
• Fatigue, weakness, weight loss, joint pain,
  abdominal pain
• A little later one
• Arthritis, dyspnea, SOB
• At the end
• Diabetes, heart failure, liver cirrhosis,
  gray/bronze skin pigmentation, severe fatigue

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How you figure out you have it

• Two blood tests
• Transferrin saturation and serum ferritin
• Need to fast before test

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Treatment of Hemochromatosis
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• Venesections (removal of blood, blood letting)
  for men.
• prolongs the life of tissue and may assist in
  reversal and prevention of damage.
• The amount of iron overload that you have will
  regulate how often you will have a venesection
• treatment usually weekly for at least 18 months,
  with follow ups for life
• Avoid Vitamin C supplements
• (helps absorb non-heme iron)
• Iron Chelators (Deferoxamine)
• Drink in moderation!!

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Cancer of the Liver type

• Primary secondary liver cancer possible
• 1 originates in the liver
• 2 originates elsewhere and spreads to liver
• Liver cancer and iron overload are linked
• Increase risk of liver cancer by 20 to 200 fold
• Greater risk if develop liver cirrhosis from the
  hemochromatosis
• Removing excess iron wont reduce risk of cancer
• Numerous other causes, including Hepatitis B C
  and aflatoxin B1
• Men are more susceptible than women

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Iron overload can cause cancer

• Modification of immune system
• transferrin-bound iron is required for T-cell
  proliferation.
• Free-iron and ferritin inhibit T-cell
  proliferation
• This results in less lymphocytes that are able to
  attack uncontrolled cell growth (cancer)
• In addition, Iron is required for DNA synthesis
  and having too much allows for rapid cancer cell
  growth.

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Liver Cancer Diagnosis and Treatment

• Diagnosed via Ultrasound, Liver biopsy, and
  symptoms
• Symptoms
• Enlarged tender liver, abdominal pain,
  unexplained weight loss, jaundice, muscle wasting
  etc.
• Treatment
• Chemotherapy, trans-arterial chemoembolization,
  Radiofrequency Ablation (lt3cm), Proton beam
  therapy (lt5cm), Surgery (lt5cm)

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Summary

• Iron is absorbed into the body in the small
  intestine
• Hemochromatosis is a result of too much iron
  entering the body.
• Iron overloading hinders the immune system by
  reducing transferrin-bound iron (required for
  T-cell proliferation), while increasing Free-iron
  and ferritin (inhibits T-cell proliferation)
• Lower T-cell proliferation results in less
  lymphocytes that are able to attack uncontrolled
  cell growth (cancer)
• Also, too much iron increases tumour growth
  capabilities (Iron is required for DNA synthesis).

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Where we got our information

• http//courses.washington.edu/conj/bess/iron/ironf
  ig.png
• http//en.wikipedia.org/wiki/IronNutrition_and_di
  etary_sources
• http//womenshealth.about.com/od/commonhealthissue
  s/a/ironoverload.htm
• http//www.medicinenet.com/liver_cancer/page2.htm
• http//digestive.niddk.nih.gov/ddiseases/pubs/hemo
  chromatosis/index.htm