Serum concentration of alpha-1 antitrypsin is significantly higher in colorectal cancer patients than in healthy controls

Abstract

BackgroundThe association between alpha-1 antitrypsin (AAT) deficiency and colorectal cancer (CRC) is currently controversial. The present study compares AAT serum concentrations and gene frequencies between a group of CRC patients and a control group of healthy unrelated people (HUP).Methods267 CRC subjects (63% males, 72 ± 10 years old) were enlisted from a Hospital Clinic setting in Asturias, Spain. The HUP group comprised 327 subjects (67% males, mean age 70 ± 7.5 years old) from the same geographical region. Outcome measures were AAT serum concentrations measured by nephelometry, and AAT phenotyping characterization by isoelectric focusing.ResultsSignificantly higher serum concentrations were found among CRC (208 ± 60) than in HUP individuals (144 ± 20.5) (p = 0.0001). No differences were found in the phenotypic distribution of the Pi*S and Pi*Z allelic frequencies (p = 0.639), although the frequency of Pi*Z was higher in CRC (21%) than in HUP subjects (15%).ConclusionsThe only statistically significant finding in this study was the markedly higher AAT serum concentrations found in CRC subjects compared with HUP controls, irrespective of whether their Pi* phenotype was normal (Pi*MM) or deficient (Pi*MS, Pi*MZ and Pi*SZ). Although there was a trend towards the more deficient Pi* phenotype the more advanced the tumor, the results were inconclusive due to the small sample size. Consequently, more powerful studies are needed to reach firmer conclusions on this matter.

Can Alpha-1 Antitrypsin be Involved in the Carcinogenesis of Colorectal Cancer?

“…Really in the present analysis the level of evidence found on this relationship is very weak, with only a study providing a 3a level of evidence [16] and all other 3b and 4 levels [15,17,20,21], according to the 2009 Oxford CEBM guidelines [19].…”

“…This study showed that in addition to the markedly elevated AAT serum levels found in CRC patients, the gene frequency of the severe deficiency Pi*Z allele, and the prevalence of the Pi*MZ, Pi*SZ and Pi*ZZ phenotypes were higher in CRC patients than in controls, but these results were inconclusive due to the small sample size [17]. This study was graded as 3b (insufficient) with the Oxford (UK) Centre for Evidence-based Medicine (CEBM) scale.…”

“…Nevertheless, several clinical studies have shown that subjects with AATD have an increased risk of developing hepatocellular carcinomas [5,6], and although not fully proved, it has been reported that AATD can favor the development of other malignances such as: lung cancer [6][7][8][9][10][11], neoplasms of the urinary bladder [12], gallbladder [13], malignant lymphomas [14], and colon carcinomas [15][16][17].…”

Neutrophilic panniculitis associated with alpha-1-antitrypsin deficiency: an update

“…Eighty percent of blood AAT diffuses into interstitial fluids, and 0Á5-10% of this reaches body fluids. 1, [3][4][5][6] Although the term 'alpha-1-antitrypsin' is widely used by clinicians and researchers, it is a misnomer. AAT was first isolated in 1955 by Herman Schultze and named 'alpha1-antitrypsin' because of the location in the alpha-1 globulin fraction and its ability to inhibit trypsin, and the term was used later when AAT deficiency was discovered by Laurell and Eriksson (Malm€ o, Sweden) in 1963.…”

Peptidomic Analysis via One-Step Direct Transfer Technology for Colorectal Cancer Biomarker Discovery

“…The following references discuss the various candidate peptides in more detail: alpha-1-antichymotrypsin [34], alpha-1-antitrypsin [35][36][37][38], alpha-2-HS-glycoprotein [20,[39][40][41][42], F. XIIIa [43], fibrinogen alpha chain [21], PF4 [21], prothrombin [43], vasodilator-stimulated phosphoprotein [44][45][46], and vinculin [47][48][49][50]. However, altered expression of these factors has not been associated with CRC and their known functions are not consistent with CRC pathology.…”