Association of Moderate Alpha-1 Antitrypsin Deficiency with Lung Cancer in the Serbian Population

Topić, Aleksandra; Jelić‐Ivanović, Zorana; Spasojević‐Kalimanovska, Vesna; Spasic, S

doi:10.1016/j.arcmed.2006.05.006

Cited by 21 publications

(24 citation statements)

References 10 publications

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“…Genetic backgrounds common to both COPD and the development of lung cancer may exist A deficiency or decrease in alpha-1 antitrypsin is known to increase the risk of lung emphysema development. This condition, acting directly or indirectly through tissue damage to the lung, also increases the risk of lung cancer development [39][40][41][42] , although some controversy regarding this point still exists [43] . Smoking is the strongest definitive risk factor for lung cancer development.…”

Section: Putative Lung Stem Cells Activated By Chronic Inflammation Imentioning

confidence: 99%

Chronic obstructive pulmonary disease as a risk factor for lung cancer

Takiguchi

Sekine

Iwasawa

et al. 2014

WJCO

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The association between chronic obstructive pulmonary disease (COPD) and lung cancer has long been a subject of intense debate. The high prevalence of COPD in elderly smokers inevitably strengthens their coincidence. In addition to this contingent coincidence, recent studies have revealed a close association between the two diseases that is independent of the smoking history; that is, the existence of COPD is an independent risk factor for the development of lung cancer. Molecular-based evidence has been accumulating as a result of the efforts to explain the underlying mechanisms of this association. These mechanisms may include the following: the retention of airborne carcinogens followed by the activation of oncogenes and the suppression of tumor suppressor genes; the complex molecular mechanism associated with chronic inflammation in the distal airways of patients with COPD; the possible involvement of putative distal airway stem cells; and genetic factors that are common to both COPD and lung cancer. The existence of COPD in patients with lung cancer may potentially affect the process of diagnosis, surgical resection, radiotherapy, chemotherapy, and end-of-life care. The comprehensive management of COPD is extremely important for the appropriate treatment of lung cancer. Surgical resections with the aid of early interventions for COPD are often possible, even for patients with mild-to-moderate COPD. New challenges, such as lung cancer CT screening for individuals at high risk, are now in the process of being implemented. Evaluating the risk of lung cancer in patients with COPD may be warranted in community-based lung cancer screening.

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Section: Putative Lung Stem Cells Activated By Chronic Inflammation Imentioning

confidence: 99%

Chronic obstructive pulmonary disease as a risk factor for lung cancer

Takiguchi

Sekine

Iwasawa

et al. 2014

WJCO

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“…However, the major association has so far been proposed for lung and liver diseases. 5,6 Proteolytic enzymes play significant roles in malignancies, invasion, and metastasis, which require degradation of the basement membrane, stimulation of angiogenesis, and migration. 7 Studies have indicated that serum levels of AAT increase in malignant diseases, such as gastrointestinal tumors, 8 prostate tumors, 9 brain tumors, 10 biliary tract cancer, 11 pancreatic adenocarcinoma, 12 breast tumors, 13 and esophageal cancer.…”

mentioning

confidence: 99%

Alpha-1 Antitrypsin Deficient Squamous Cell Carcinoma of Esophagus in the Azeri Population of Iran

Ganji

Sahebghadam-Lotfi

Rastgar-Jazii

et al. 2010

Lab Med

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Alpha-1 antitrypsin (AAT) is a member of the serine protease inhibitors (serpins) family. Hepatocytes are the major source of synthesis and secretion of AAT into the blood stream. However, macrophages of the lungs also take part in this process to a lower extent. 1 Alpha-1 antitrypsin diffuses into tissues where it targets neutrophil elastase, a powerful protease capable of cleaving elastic fibers of alveolar walls and other structural proteins. 2 Being the most abundant human serum protease inhibitor, AAT is encoded by a single gene of 12.2 kb, which is located on the long arm of chromosome 14 (14q31-32.2). The protein is highly polymorphic, and a number of alleles have so far been identified in this regard. These alleles are categorized into the following 4 groups: 1) a normal allele, whose product is AAT with normal function and serum levels ranging from 150 up to 350 mg/dL -1 ; 2) deficient alleles associated with serum AAT levels less than 35% of those of normal subjects, which may or may not function normally; 3) null alleles displaying no detectable serum AAT levels; and 4) dysfunctional alleles. The last group encodes AAT present at normal levels that is not functional. 3,4 Mutations in the AAT gene have shown to be associated with a number of diseases, including renal, arthritis, and malignancies. However, the major association has so far been proposed for lung and liver diseases. 5,6 Proteolytic enzymes play significant roles in malignancies, invasion, and metastasis, which require degradation of the basement membrane, stimulation of angiogenesis, and migration. 7 Studies have indicated that serum levels of AAT increase in malignant diseases, such as gastrointestinal tumors, 8 prostate tumors, 9 brain tumors, 10 biliary tract cancer, 11 pancreatic adenocarcinoma, 12 breast tumors, 13 and esophageal cancer. 14 A significant correlation between serum AAT levels and cancer stage has also been proposed. 15,16 A change in the levels of a particular protease relative to its inhibitor accounts for the increased potential of tumor formation. 16 Esophageal cancer ranks among the top 10 most frequent cancers, characterized by poor prognosis and a 5-year survival rate of less than 10%. Despite many efforts and investigations, the mechanism underlying the development of esophageal Abstract Background: Alpha-1 antitrypsin (AAT) deficiency is an inherited disease characterized by reduced levels of AAT in the serum. The 2 common genotypes of AAT deficiency are type Z (PiZ) and type S (PiS), which are associated with several malignancies.

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“…Mutations in the AAT gene has shown to be associated with a number of diseases including Cirrhosis, COPD, pneumothorax, asthma, wegener's granulomatosis, pancreatitis , gallstones, bronchiectasis, pelvic organ prolapse, primary sclerosing cholangitis, autoimmune hepatitis, emphysema (predominantly involving the lower lobes and causing bullae), renal, and arthritis. In addition in other malignancies such as Hepatocellular carcinoma, Bladder carcinoma, Gallbladder cancer, Lymphoma, and lung cancer defects and mutations of AAT have also been reported [7,8].…”

Section: Introductionmentioning

confidence: 99%