Hemochromatosis (HHC) is an inherited condition that causes the body to absorb an excessive amount of iron from the diet. This surplus iron is deposited in various organs, most notably the liver, but also the heart, pancreas, and joints. Since the body lacks a mechanism to excrete this excess iron, the result is iron overload. Over time, this accumulation causes progressive tissue damage and organ dysfunction.
Specific Cancer Risks Associated with Iron Overload
The most significant cancer risk associated with untreated hemochromatosis is Hepatocellular Carcinoma (HCC), the most common form of primary liver cancer. The liver is the main storage site for excess iron, making it the most vulnerable organ to iron-related damage. Chronic iron overload frequently leads to inflammation, scarring, and ultimately, cirrhosis.
Cirrhosis acts as a major precursor, increasing the likelihood of malignant transformation in the liver tissue. The risk of developing HCC is substantially higher in patients who have already developed cirrhosis at the time of diagnosis. The presence of cirrhosis is considered the most important factor determining cancer risk in these patients.
Although the connection is strongest for HCC, generalized iron toxicity may contribute to an elevated risk for cancers in other iron-sensitive organs, such as the pancreas. The most established link remains the progression from iron-induced liver damage to liver cancer. Early detection and management are paramount to interrupting this progression.
How Excess Iron Causes Cellular Damage
The connection between elevated iron levels and cancer development is rooted in iron’s function as a pro-oxidant, a molecule that promotes oxidative reactions. While iron is normally bound to proteins for safe transport and storage, the excessive, unbound iron in hemochromatosis enters a highly reactive state. This unbound iron participates in the Fenton reaction within cells.
The Fenton reaction involves free iron reacting with hydrogen peroxide to generate highly unstable molecules called reactive oxygen species (ROS), or free radicals. This reaction specifically produces the hydroxyl radical, which is one of the most destructive free radicals in biology. These hydroxyl radicals indiscriminately attack nearby cellular structures.
The resulting oxidative stress causes widespread damage to cellular components. Free radicals can destroy cell membranes (lipids), alter the function of cellular machinery (proteins), and cause modifications and breaks in the cell’s genetic material (DNA). Damage to DNA is a fundamental step in cancer development, as these mutations can turn off tumor-suppressing genes or activate genes that promote uncontrolled cell growth.
This mechanism is amplified in the liver because it is the primary site of iron deposition, leading to a high local concentration of free iron and subsequent oxidative damage. The continuous cycle of injury and repair in the liver tissue further increases the chance of a cancerous mutation taking hold.
Treatment and Risk Reduction Strategies
The standard and most effective treatment for reducing cancer risk is therapeutic phlebotomy, a simple procedure involving the removal of blood, similar to a blood donation. The goal is to safely and gradually deplete the body’s iron stores.
Removing blood causes the body to draw iron out of the organs, including the liver, to produce new red blood cells. The initial phase involves frequent phlebotomies, often weekly, until the body’s iron levels—measured by the iron storage protein ferritin—fall into the normal range. Once iron is lowered, a lifelong maintenance phase begins with less frequent blood removal to keep the level stable.
Early diagnosis and consistent adherence to the regimen are paramount for preventing severe complications. If treatment starts before the onset of permanent organ damage like cirrhosis, patients can expect a normal life expectancy, and the risk of liver cancer is virtually eliminated. For individuals who have already developed cirrhosis, phlebotomy prevents further iron accumulation, but the risk of HCC remains, necessitating continued cancer screening.