Rare disorder that causes liver and lung disease increases the risk of developing several types of cancer

Health and Wellness 31. okt 2024 2 min Clinical Professor Morten Dahl Written by Kristian Sjøgren

A new study shows that people with the rare genetic disorder a1-antitrypsin deficiency face its direct effects and an increased risk of several types of cancer. A researcher says that some groups of people should perhaps be especially aware of this increased cancer risk.

Some people have a1-antitrypsin deficiency, a very rare disorder caused by a gene variant that leads to early-onset emphysema and liver cirrhosis.

A new study shows that people with a1-antitrypsin deficiency have an increased risk of cancer, with very specific types of cancer being more frequent than in the general population.

Although the risk is not tremendously increased, a researcher behind the study says that some groups of people with a1-antitrypsin deficiency have additional increased risk and should be especially aware of signs of early-onset cancer.

“These people know that they have an increased risk of developing liver cancer, but we identified two additional types of cancer that are more frequent among people with a1-antitrypsin deficiency than in the rest of the population. Some people with this deficiency should perhaps be especially aware of the need to be examined,” explains Morten Dahl, Clinical Professor, Department of Clinical Medicine, University of Copenhagen, Denmark.

The research has been published in the Journal of Internal Medicine.

A cascade effect

People with a1-antitrypsin deficiency can be affected throughout their body. In addition to diseases in the liver and lungs, a1-antitrypsin deficiency is associated with elevated activity of neutrophil elastase, an enzyme released from inflammatory cells.

a1-antitrypsin suppresses the activity of neutrophil elastase from the inflammatory cells. In accordance with this, a lack of a1-antitrypsin in the circulation increases this activity.

Previous studies have also shown that increased production of neutrophil elastase is clearly linked to the proliferation of cancer cells while the gene encoding a1-antitrypsin is overexpressed.

“People with a1-antitrypsin deficiency accumulate a1-antitrypsin in their liver cells, which contributes to an increased risk of developing liver cancer. In this study, we aimed to investigate whether a1-antitrypsin deficiency and the associated increased activity of neutrophil elastase are associated with an increased risk of developing other types of cancer,” says Morten Dahl.

2,702 participants with a1-antitrypsin deficiency

The researchers identified 2,702 people with a1-antitrypsin deficiency and matched the study group in terms of age, sex and municipality of residence with 10 times as many people from the background population. They then compared the incidence of several types of cancer in these groups.

The researchers followed the people with a1-antitrypsin deficiency and the controls in Denmark’s health registries for up to 67 years.

Denmark’s health registries are world famous for the potential of following a population and their illnesses from cradle to grave.

Increased risk of developing skin cancer

The comparison showed that people with a1-antitrypsin deficiency have an increased risk of developing not only liver cancer but also other types of cancer.

The risk of developing liver cancer remained the most elevated, with a 3.91-fold increased risk among people with a1-antitrypsin deficiency compared with the general population.

However, the researchers also found that people with a1-antitrypsin deficiency had a 2.18-fold increased risk of developing skin cancer and a 1.76-fold increased risk of developing leukaemia.

The researchers linked having a diagnosis of a1-antitrypsin deficiency to an increased risk of developing non-melanoma skin cancer but not melanoma.

Finally, the researchers also found that people with a1-antitrypsin deficiency who had also been diagnosed with chronic obstructive pulmonary disease had a very high risk of developing skin cancer.

The risk increased as much as 3.59-fold. If people had a skin disease, the risk increased 2.93-fold.

“The increased risk of skin cancer is especially interesting because it is a new finding and also a relatively common type of cancer and the most common type of skin cancer associated with sun damage according to WHO,” explains Morten Dahl.

Some groups can be especially affected

Morten Dahl is not surprised that people with a1-antitrypsin deficiency have an increased risk of skin cancer because it is already well known that increased activity of neutrophil elastase in the skin increases the risk of skin cancer precursors.

However, a1-antitrypsin deficiency has not been previously linked to an increased risk of skin cancer.

In addition, further investigating whether groups can be identified that should be especially aware of their cancer risk could be interesting.

“Some groups of people with a1-antitrypsin deficiency may have a very high risk of skin cancer, and being more aware of getting examined if they find something on their skin that does not look right may be relevant,” concludes Morten Dahl.

The Department of Clinical Medicine's research is carried out at research centres and hospitals in the Capital Region of Denmark and Region Zealand wh...

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