The connection between inflammation and the genesis of cancer is well-known. However, not all cases of inflammation are accompanied by an increased risk of cancer. For instance, patients with allergic diseases, rheumatoid arthritis or myocarditis display no increased risk for developing cancer. The question therefore arises, why certain persistent inflammatory conditions promote carcinogenesis, while others do not.
Increased concentrations of acute phase proteins are often connected with a poorer prognosis for malignant tumors. Thus, alpha-1 antitrypsin (AAT) as an acute phase protein also plays a role in carcinogenesis. Earlier studies have shown that AAT is involved in the metastatic growth of various types of cancer, including ovarian, throat, stomach, breast and lung adenocarcinomas (details under www.lungenaerzte-im-netz.de/krankheiten/lungenkrebs/krankheitsbild/).
Increased serum levels of AAT have been detected in patients with carcinomas, for example in the pancreas, prostate gland, cervix, ovaries, breast, Hodgkin’s lymphoma and larynx and have been suggested as useful prognostic factors. In accordance with this, our own results from more than 300 patients with non-small cell lung cancer confirmed that higher serum levels of AAT prognostically indicate a worse course of disease. Why is it so? As a reaction, particularly to inflammatory stimuli, various cancer cells express the AAT protein. In previous studies we were able to show that AAT can significantly strengthen the migration, invasiveness and viability of lung cancer cells.
What is the situation with people with congenital AAT deficiency? A severe AAT deficiency is a risk factor for the development of hepatocarcinomas. This occurs through accumulated polymers of the misfolded AATs and insufficient regeneration of the liver cells. Data from the Swedish AATM Register show the diagnosis of hepatocellular carcinoma in 32 out of 1595 people with PiZZ, which is a share of 2%. According to estimations in the year 2012, the frequency rate for hepatocarcinomas per 100,000 inhabitants in Northern Europe was 4.6 cases, in Southern Europe 9.5 cases and in North America 9.3 cases, depending on the study.
Other reports show that people with AAT deficiency generally have a lower or no increased risk of developing lung and probably also other types of cancer. For instance, results from a cross-sectional study of 720 people with AAT deficiency in the Alpha-1 Foundation Research Registry at the Medical University of South Carolina, showed that only 8 (1.1%) of them were diagnosed with lung cancer.
In accordance with this is the comparison of 1,585 PiZZ test persons from the Swedish AATM Register and 5,999 people from the control group. This has shown that deaths due to cancer among those with PiZZ were, at 11%, less frequent than in the control group at 33%. With regard to lung cancer as a cause of death, 1% of the PiZZ test persons and 4% of the control group were affected.The connection between inflammation and the genesis of cancer is well-known. However, not all cases of inflammation are accompanied by an increased risk of cancer. For instance, patients with allergic diseases, rheumatoid arthritis or myocarditis display no increased risk for developing cancer. The question therefore arises, why certain persistent inflammatory conditions promote carcinogenesis, while others do not.
Increased concentrations of acute phase proteins are often connected with a poorer prognosis for malignant tumors. Thus, alpha-1 antitrypsin (AAT) as an acute phase protein also plays a role in carcinogenesis. Earlier studies have shown that AAT is involved in the metastatic growth of various types of cancer, including ovarian, throat, stomach, breast and lung adenocarcinomas (details under www.lungenaerzte-im-netz.de/krankheiten/lungenkrebs/krankheitsbild/).
Increased serum levels of AAT have been detected in patients with carcinomas, for example in the pancreas, prostate gland, cervix, ovaries, breast, Hodgkin’s lymphoma and larynx and have been suggested as useful prognostic factors. In accordance with this, our own results from more than 300 patients with non-small cell lung cancer confirmed that higher serum levels of AAT prognostically indicate a worse course of disease. Why is it so? As a reaction, particularly to inflammatory stimuli, various cancer cells express the AAT protein. In previous studies we were able to show that AAT can significantly strengthen the migration, invasiveness and viability of lung cancer cells.
What is the situation with people with congenital AAT deficiency? A severe AAT deficiency is a risk factor for the development of hepatocarcinomas. This occurs through accumulated polymers of the misfolded AATs and insufficient regeneration of the liver cells. Data from the Swedish AATM Register show the diagnosis of hepatocellular carcinoma in 32 out of 1595 people with PiZZ, which is a share of 2%. According to estimations in the year 2012, the frequency rate for hepatocarcinomas per 100,000 inhabitants in Northern Europe was 4.6 cases, in Southern Europe 9.5 cases and in North America 9.3 cases, depending on the study.
Other reports show that people with AAT deficiency generally have a lower or no increased risk of developing lung and probably also other types of cancer. For instance, results from a cross-sectional study of 720 people with AAT deficiency in the Alpha-1 Foundation Research Registry at the Medical University of South Carolina, showed that only 8 (1.1%) of them were diagnosed with lung cancer.
In accordance with this is the comparison of 1,585 PiZZ test persons from the Swedish AATM Register and 5,999 people from the control group. This has shown that deaths due to cancer among those with PiZZ were, at 11%, less frequent than in the control group at 33%. With regard to lung cancer as a cause of death, 1% of the PiZZ test persons and 4% of the control group were affected.

At the start of 2019, the patient organization Alpha1 Deutschland sent out a survey to about 400 PiZZlers, to gather information about possible cancer diagnoses. A total of 111 persons (62 men and 45 women aged between 31-90 years) responded to the survey. Of these 111, 82 (73.9%) receive an ATT substitution therapy, while 29 (26.1%) will not be substituted. Overall, 20 participants (18%) reported a cancer diagnosis.
The current literature and our own observations indicate that an AAT deficiency could be connected with a lower risk of cancer development. Nevertheless, large, prospective studies (that are concerned with further development) as well as studies investigating the relationships between AAT gene variants and cancer are necessary in order to determine the role of AAT in the development and course of cancer.

Source: Edition 2/2019 Alpha1-Journal

Picutre: MHH/ Tom Figiel