A poluição do ar e o sistema respiratório

A poluição atmosférica encontra-se presente nos mais diferentes cenários ao longo dos últimos 250 anos, desde que a Revolução Industrial acelerou o processo de emissão de poluentes que, até então, estava limitado ao uso doméstico de combustíveis vegetais e minerais e às emissões vulcânicas intermitentes. Hoje, aproximadamente 50% da população do planeta vivem em cidades e aglomerados urbanos e estão expostas a níveis progressivamente maiores de poluentes do ar. Este estudo é uma revisão não sistemática sobre os diferentes tipos e fontes de poluentes do ar e os efeitos respiratórios atribuídos à exposição a esses contaminantes. Podem ser creditados aos poluentes particulados e gasosos, emitidos por diferentes fontes, aumentos nos sintomas de doenças, na procura por atendimentos em serviços de emergência e no número de internações e de óbitos. Mais do que descompensar doenças pré-existentes, exposições crônicas têm ajudado a aumentar o número de casos novos de asma, de DPOC e de câncer de pulmão, tanto em áreas urbanas quanto em áreas rurais, fazendo com que os poluentes atmosféricos rivalizem com a fumaça do tabaco pelo papel de principal fator de risco para estas doenças. Na rotina de clínicos e pneumologistas, esperamos contribuir para consolidar a importância da investigação sobre a exposição aos poluentes do ar e o reconhecimento de que esse fator de risco merece ser levado em conta na adoção da melhor terapêutica para o controle das descompensações agudas das doenças respiratórias e para a sua manutenção entre as crises.

Metabolismo di oligosaccaridi prebiotici in Bifidobacterium per il potenziale sviluppo di nuovi prodotti alimentari funzionali

The growth and the metabolism of Bifidobacterium adolescentis MB 239 fermenting GOS, lactose, galactose, and glucose were investigated. An unstructerd unsegregated model for growth of B. adolescentis MB 239 in batch cultures was developed and kinetic parameters were calculated with a Matlab algorithm. Galactose was the best carbon source; lactose and GOS led to lower growth rate and cellular yield, but glucose was the poorest carbon source. Lactate, acetate and ethanol yields allowed calculation of the carbon fluxes toward fermentation products. Similar distribution between 3- and 2-carbon products was observed on all the carbohydrates (45 and 55%, respectively), but ethanol production was higher on glucose than on GOS, lactose and galactose, in decreasing order. Based on the stoichiometry of the fructose 6-phosphate shunt and on the carbon distribution among the products, ATP yield was calculated on the different carbohydrates. ATP yield was the highest on galactose, while it was 5, 8, and 25% lower on lactose, GOS, and glucose, respectively. Therefore, a correspondance among ethanol production, low ATP yields, and low biomass production was established demonstrating that carbohydrate preferences may result from different sorting of carbon fluxes through the fermentative pathway. During GOS fermentation, stringent selectivity based on the degree of polymerization was exhibited, since lactose and the trisaccharide were first to be consumed, and a delay was observed until longer oligosaccharides were utilized. Throughout the growth on both lactose and GOS, galactose accumulated in the cultural broth, suggesting that β-(1-4) galactosides can be hydrolysed before they are taken up. The physiology of Bifidobacterium adolescentis MB 239 toward xylooligosaccharides (XOS) was also studied and our attention was focused on an extracellular glycosyl-hydrolase (β-Xylosidase) expressed by a culture of B. adolescentis grown on XOS as sole carbon source. The extracellular enzyme was purified from the the supernatant, which was dialyzed and concentrated by ultrafiltration. A two steps purification protocol was developed: the sample was loaded on a Mono-Q anion exchange chromatography and then, the active fractions were pooled and β-Xylosidase was purified by gel filtration chromatography on a Superdex-75. The enzyme was characterized in many aspects. β- Xylosidase was an homo-tetramer of 160 kDa as native molecular mass; it was a termostable enzyme with an optimum of temperature at 53 °C and an optimum of pH of 6.0. The kinetics parameter were calculated: km = 4.36 mM, Vmax = 0.93 mM/min. The substrate specificity with different di-, oligo- and polysaccharides was tested. The reactions were carried out overnight at pH 7 and at the optimum of temperature and the carbohydrates hydrolysis were analyzed by thin layer chromatography (TLC). Only glycosyl-hydrolase activities on XOS and on xylan were detected, whereas sucrose, lactose, cellobiose, maltose and raffinose were not hydrolyzed. It’s clearly shown that β-Xylosidase activity was higher than the Xylanase one. These studies on the carbohydrate preference of a strain of Bifidobacterium underlined the importance of the affinity between probiotics and prebiotics. On the basis of this concept, together with Barilla G&R f.lli SpA, we studied the possibility to develop a functional food containing a synbiotic. Three probiotic strains Lactobacillus plantarum BAR 10, Streptococcus thermophilus BAR 20, and Bifidobacterium lactis BAR 30 were studied to assess their suitability for utilization in synbiotic products on the basis of antioxidative activity, glutathione production, acid and bile tolerance, carbohydrates fermentation and viability in food matrices. Bile and human gastric juice resistance was tested in vitro to estimate the transit tolerance in the upper gastrointestinal tract. B. lactis and L. plantarum were more acid tolerant than S. thermophilus. All the strains resisted to bile. The growth kinetics on 13 prebiotic carbohydrates were determined. Galactooligosaccharides and fructo-oligosaccharides were successfully utilized by all the strains and could be considered the most appropriate prebiotics to be used in effective synbiotic formulations. The vitality of the three strains inoculated in different food matrices and maintained at room temperature was studied. The best survival of Lactobacillus plantarum BAR 10, Streptococcus thermophilus BAR 20, and Bifidobacterium lactis BAR 30 was found in food chocolate matrices. Then an in vivo clinical trial was carried out for 20 healthy volunteers. The increase in faecal bifidobacteria and lactobacilli populations and the efficacy of the pre-prototype was promising for the future develop of potential commercial products.

Study of two novel streptococcus pneumoniae operons: pilus islet 2 and the lantibiotic operon

Analysis of publicly available genomes of Streptococcus pneumoniae has led to the identification of a new genomic element resembling gram-positive pilus islets (PIs). Here, we demonstrate that this genomic region, herein referred to as PI-2 (containing the genes pitA, sipA, pitB, srtG1, and srtG2) codes for a novel functional pilus in pneumococcus. Therefore, there are two pilus islets identified so far in this pathogen (PI-1 and PI-2). Polymerization of the PI-2 pilus requires the backbone protein PitB as well as the sortase SrtG1 and the signal peptidase-like protein SipA. PI-2 is associated with serotypes 1, 2, 7F, 19A, and 19F, considered to be emerging in both industrialized and developing countries. Interestingly, strains belonging to clonal complex 271 (CC271) contain both PI-1 and PI-2, as revealed by genome analyses. In these strains both pili are surface exposed and independently assembled. Furthermore, in vitro experiments provide evidence that the pilus encoded by PI-2 of S. pneumoniae is involved in adherence. Thus, pneumococci encode at least two types of pili that may play a role in the initial host cell contact to the respiratory tract. In addition, the pilus proteins are potential antigens for inclusion in a new generation of pneumococcal vaccines. Adherence by pili could represent important factor in bacterial community formation, since it has been demonstrated that bacterial community formation plays an important role in pneumococcal otitis media. In vitro quantification of bacterial community formation by S. pneumoniae was performed in order to investigate the possible role of pneumococcal pili to form communities. By using different growth media we were not able to see clear association between pili and community formation. But our findings revealed that strains belonging to MLST clonal complex CC15 efficiently form bacterial communities in vitro in a glucose dependent manner. We compared the genome of forty-four pneumococcal isolates discovering four open reading frames specifically associated with CC15. These four genes are annotated as members of an operon responsible for the biosynthesis of a putative lanctibiotic peptide, described to be involved in bacterial community formation. Our experiments show that the lanctibiotic operon deletion affects glucose mediated community formation in CC 15 strain INV200. Moreover, since glucose consumption during bacterial growth produce an acidic environment, we tested bacterial community formation at different pH and we showed that the lanctibiotic operon deletion affected pH mediated community formation in CC 15 strain INV200. In conclusion, these data demonstrate that the putative lanctibiotic operon is associated with pneumococcal CC 15 strains in vitro bacterial community formation.

Entwicklung eines Tests zur Ablösung von Tierversuchen beim Nachweis von Pertussis-Toxin

Weltweit existiert keine zum Tierversuch alternative Methode, um adsorbierte Pertussis-Impfstoffe auf restliche Toxin-Aktivität hin zu untersuchen. Der im Europäischen Arzneibuch vorgeschriebene Tierversuch besitzt nach Erfahrungen der Industrie, internationaler Prüfbehörden sowie des Paul-Ehrlich-Institutes eine schlechte Aussagekraft. Er ist wenig standardisierbar und weist häufig ein zweifelhaftes Ergebnis auf, so dass Wiederholungen und damit einhergehend ein hoher Verbrauch an Versuchstieren unumgänglich sind. Enthält der Impfstoff Reste von nicht-inaktiviertem Pertussis-Toxin (PTx), muss mit schweren und schwersten Nebenwirkungen bei den Impflingen gerechnet werden. In dieser Arbeit wurde ein In vitro-Nachweis für aktives PTx entwickelt. rnAngeregt durch Publikationen, wonach Pertussis-Toxin humane Monozyten aktiviert, wurde zunächst versucht, diesen Effekt zum Toxin-Nachweis auszunutzen. Die vorliegende Arbeit zeigt jedoch eindeutig, dass Pertussis-Toxin selbst nicht zur Stimulation humaner Monozyten führt. Vielmehr konnte nachgewiesen werden, dass die Aktivierung dieser Immunzellen auf Kontaminationen durch Lipopolysaccharide zurückzuführen ist. Damit wurden die Aussagen in den oben erwähnten Veröffentlichungen widerlegt. Dieses Ergebnis wurde bereits zur Publikation eingereicht.rnNunmehr wurden verschiedene Ansätze zum Nachweis von Pertussis-Toxin entwickelt, welche seine enzymatischen Aktivitäten als NAD-Glycohydrolase und ADP-Ribosyltransferase ausnutzen. Zunächst wurde versucht, die Hydrolyse von NAD zu ADP-Ribose und Nicotinamid photometrisch nachzuweisen. Wegen unbefriedigender Sensitivität wurde dieses Verfahren zu einem fluorometrischen Nachweis weiterentwickelt. Verwendet wurde hier fluorogenes etheno-NAD, welches von Pertussis-Toxin als Substrat akzeptiert wird. Letzteres Prinzip ist zum In vitro-Nachweis von Pertussis-Toxin geeignet, wird jedoch durch das in Impfstoffen häufig verwendete Adsorbens Aluminiumhydroxid gestört. Deshalb wurde dieser Ansatz aufgegeben und ein neuer Weg verfolgt, welcher am Energiestoffwechsel von humanen Zellen ansetzt. Eine Konsequenz des Angriffs von Pertussis-Toxin auf seine Zielzellen im Respirationstrakt besteht – nach komplexen Reaktionen des Signaltransduktionsweges – im Absenken des ATP-Gehaltes. Als menschliche Surrogat-Zellen wurden frisch isolierte periphere mononukleäre Zellen (PBMCs) sowie die permanente Lymphozyten-Zelllinie Jurkat eingesetzt und deren ATP-Gehalt mittels Luziferin-Luziferase-Lumineszenz gemessen. Der Test wird nicht durch Lipopolysaccharid gestört und auch Aluminiumhydroxid übt erst nach mehreren Stunden Inkubation einen interferierenden Einfluss aus. Ebenso konnte aktives Pertussis-Toxin mit Hilfe kryokonservierter PBMCs detektiert werden, auch in orientierenden Versuchen mit komplexen Impfstoffen. Der Pertussis-ATP-Test kommt der In vivo-Situation in der Zelle sehr nahe, weil beide Untereinheiten des Toxins in einem Test überprüft werden. Demnach soll er Bestandteil einer geplanten internationalen Studie zu alternativen Pertussis-Toxin-Testungen sein.

Vascularised fibula grafts for early tibia reconstruction in infants with congenital pseudarthrosis

Congenital pseudarthrosis of the tibia (CPT) is caused by an ill-defined, segmental disturbance of periosteal bone formation leading to spontaneous bowing, followed by fracture and subsequent pseudarthrosis in the first 2 years of life. The results of conventional treatment modalities (e.g., bracing, internal and external fixation and bone grafting) are associated with high failure rates in terms of persisting pseudarthrosis, malunion and impaired growth. As a more promising alternative, a more aggressive approach, including wide resection of the affected bone, reconstruction with free vascularised fibula grafts from the healthy contralateral leg and stable external fixation at a very early stage has been suggested. Between 1995 and 2007, 10 children (age 12-31 months, median 20 months) suffering from CPT were treated at our institutions according to this principle. Two patients were treated before a fracture had occurred. The length of the fibula graft was 7-9cm. End-to-end anastomoses were performed at the level of the distal tibia stump. The follow-up was 80 months (median, range 12 months to 12 years). Radiologic examination at 6 weeks postoperatively showed normal bone density and structure of the transplanted fibula in all cases and osseous consolidation at 19 of the 20 graft/tibia junctions. One nonunion was sucessfully treated with bone grafting and plate osteosynthesis. Pin-tract infection occurred in three patients. Five children sustained graft fractures that were successfully treated with internal or external fixation. Two patients developed diminished growth of the affected limb or foot; all others had equal limb length and shoe size. At long-term follow-up, tibialisation of the transplant had occurred, and normal gait and physical activities were possible in all children. We conclude that in spite of a relatively high complication rate and the reluctance to perform free flap surgery in infants at this young age, the present concept may successfully prevent the imminent severe sequelae associated with CPT.

Hemolytic-uremic syndrome in Switzerland: a nationwide surveillance 1997-2003

Hemolytic-uremic syndrome (HUS) is a leading cause of acute renal failure in childhood. In its typical presentation, it is preceded by an episode of diarrhea mostly due to Shiga-toxin-producing Escherichia coli. There is important geographical variation of many aspects of this syndrome. Nationwide data on childhood HUS in Switzerland have not been available so far. In a prospective national study through the Swiss Pediatric Surveillance Unit 114 cases (median age 21 months, 50% boys) were reported between April 1997 and March 2003 by 38 pediatric units (annual incidence 1.42 per 10(5) children < or =16 years). Shiga-toxin-producing E. coli were isolated in 32 (60%) of tested stool samples, serotype O157:H7 in eight. Sixteen children presented with only minimal renal involvement, including three with underlying urinary tract infection. Six patients presented with atypical hemolytic-uremic syndrome, and six with HUS due to invasive Streptococcus pneumoniae infection. Mortality was 5.3%, including two out of six children with S. pneumoniae infection. The severity of thrombocytopenia and the presence of central nervous system involvement significantly correlated with mortality. In conclusion, childhood HUS is not rare in Switzerland. Contrasting other countries, E. coli O157:H7 play only a minor role in the etiology. Incomplete manifestation is not uncommon.

Hypokalemic rhabdomyolyisis in congenital tubular disorders: a case series and a systematic review

Hypokalemia is a recognized cause of rhabdomyolysis but very few reports document its association with inborn renal tubular disorders. We report our experience with hypokalemic rhabdomyolysis in 5 pediatric patients affected by inborn renal tubular disorders and the results of a careful review of the literature disclosing 9 further cases for a total of 14 patients (8 male and 6 female subjects, aged between 1.6 and 46, median 16 years). The inborn renal tubular disorders underlying rhabdomyolysis were classic distal renal tubular acidosis (n = 7), Gitelman syndrome (n = 5), classic Bartter syndrome (n = 1), and antenatal Bartter syndrome (n = 1). In 8 patients rhabdomyolysis followed an acute intestinal disease, an upper respiratory illness or the discontinuation of regular medication. Five patients experienced two or more episodes of rhabdomyolysis. In 10 patients the underlying renal tubular disorder was recognized concurrently with the episode of rhabdomyolysis or some weeks later. In conclusion some congenital renal tubular disorders predispose to hypokalemic rhabdomyolysis. Prevention of discontinuation of regular medication and electrolyte repair in the context of acute intercurrent illnesses might avoid the development of hypokalemic rhabdomyolysis.

Deposition and biokinetics of inhaled nanoparticles

Particle biokinetics is important in hazard identification and characterization of inhaled particles. Such studies intend to convert external to internal exposure or biologically effective dose, and may help to set limits in that way. Here we focus on the biokinetics of inhaled nanometer sized particles in comparison to micrometer sized ones.The presented approach ranges from inhaled particle deposition probability and retention in the respiratory tract to biokinetics and clearance of particles out of the respiratory tract. Particle transport into the blood circulation (translocation), towards secondary target organs and tissues (accumulation), and out of the body (clearance) is considered. The macroscopically assessed amount of particles in the respiratory tract and secondary target organs provides dose estimates for toxicological studies on the level of the whole organism. Complementary, microscopic analyses at the individual particle level provide detailed information about which cells and subcellular components are the target of inhaled particles. These studies contribute to shed light on mechanisms and modes of action eventually leading to adverse health effects by inhaled nanoparticles.We review current methods for macroscopic and microscopic analyses of particle deposition, retention and clearance. Existing macroscopic knowledge on particle biokinetics and microscopic views on particle organ interactions are discussed comparing nanometer and micrometer sized particles. We emphasize the importance for quantitative analyses and the use of particle doses derived from real world exposures.

Recent advances into understanding some aspects of the structure and function of mammalian and avian lungs

Recent findings are reported about certain aspects of the structure and function of the mammalian and avian lungs that include (a) the architecture of the air capillaries (ACs) and the blood capillaries (BCs); (b) the pulmonary blood capillary circulatory dynamics; (c) the adaptive molecular, cellular, biochemical, compositional, and developmental characteristics of the surfactant system; (d) the mechanisms of the translocation of fine and ultrafine particles across the airway epithelial barrier; and (e) the particle-cell interactions in the pulmonary airways. In the lung of the Muscovy duck Cairina moschata, at least, the ACs are rotund structures that are interconnected by narrow cylindrical sections, while the BCs comprise segments that are almost as long as they are wide. In contrast to the mammalian pulmonary BCs, which are highly compliant, those of birds practically behave like rigid tubes. Diving pressure has been a very powerful directional selection force that has influenced phenotypic changes in surfactant composition and function in lungs of marine mammals. After nanosized particulates are deposited on the respiratory tract of healthy human subjects, some reach organs such as the brain with potentially serious health implications. Finally, in the mammalian lung, dendritic cells of the pulmonary airways are powerful agents in engulfing deposited particles, and in birds, macrophages and erythrocytes are ardent phagocytizing cellular agents. The morphology of the lung that allows it to perform different functions-including gas exchange, ventilation of the lung by being compliant, defense, and secretion of important pharmacological factors-is reflected in its "compromise design."

Extended lymph node dissection: bladder, kidney

To present recent advances in the field of lymph node dissection (LND) in the context of bladder cancer, upper urinary tract urothelial carcinoma and renal cell carcinoma with focus on dissection extent.

Percutaneous endoscopic gastrostomy in head and neck cancer patients: indications, techniques, complications and results

The aim of this study was to review our experience in percutaneous endoscopic gastrostomy (PEG) performed in patients with cancer of the upper aerodigestive tract. Descriptive retrospective study of 142 patients (115 males, 27 females), mean age 62.4 years (25-84 years), with head and neck or esophageal cancer, who underwent PEG tube insertion between January 2006 and December 2008. The studied parameters were indications, success rate, rate and type of complications, and their management. Percutaneous endoscopic gastrostomy was inserted before chemoradiation therapy in 80% and during or after cancer treatment in 20% of the patients. PEG placement was possible in 137 patients (96%). Major complications were observed in 9 (7%) and minor complications in 22 (17%) of the 137 patients. Seven of the 9 patients with a major complication needed revision surgery. The mortality directly related to the procedure was 0.7%. Percutaneous endoscopic gastrostomy tube insertion has a high success rate. In patients with upper aerodigestive tract cancer, PEG should be the first choice for enteral nutrition when sufficient oral intake is not possible. Although apparently easy, the procedure may occasionally lead to severe complications. Therefore, a strict technique and knowledge of clinical signs of possible complications are mandatory.

Physiologic cold shock of Moraxella catarrhalis affects the expression of genes involved in the iron acquisition, serum resistance and immune evasion

Background Moraxella catarrhalis, a major nasopharyngeal pathogen of the human respiratory tract, is exposed to rapid downshifts of environmental temperature when humans breathe cold air. It was previously shown that the prevalence of pharyngeal colonization and respiratory tract infections caused by M. catarrhalis are greatest in winter. The aim of this study was to investigate how M. catarrhalis uses the physiologic exposure to cold air to upregulate pivotal survival systems in the pharynx that may contribute to M. catarrhalis virulence. Results A 26°C cold shock induces the expression of genes involved in transferrin and lactoferrin acquisition, and enhances binding of these proteins on the surface of M. catarrhalis. Exposure of M. catarrhalis to 26°C upregulates the expression of UspA2, a major outer membrane protein involved in serum resistance, leading to improved binding of vitronectin which neutralizes the lethal effect of human complement. In contrast, cold shock decreases the expression of Hemagglutinin, a major adhesin, which mediates B cell response, and reduces immunoglobulin D-binding on the surface of M. catarrhalis. Conclusion Cold shock of M. catarrhalis induces the expression of genes involved in iron acquisition, serum resistance and immune evasion. Thus, cold shock at a physiologically relevant temperature of 26°C induces in M. catarrhalis a complex of adaptive mechanisms that enables the bacterium to target their host cellular receptors or soluble effectors and may contribute to enhanced growth, colonization and virulence.

Actinobaculum schaalii an emerging pediatric pathogen?

Background Actinobaculum schaalii was first described as a causative agent for human infection in 1997. Since then it has mainly been reported causing urinary tract infections (UTI) in elderly individuals with underlying urological diseases. Isolation and identification is challenging and often needs molecular techniques. A. schaalii is increasingly reported as a cause of infection in humans, however data in children is very limited. Case presentation We present the case of an 8-month-old Caucasian boy suffering from myelomeningocele and neurogenic bladder who presented with a UTI. An ultrasound of the urinary tract was unremarkable. Urinalysis and microscopy showed an elevated leukocyte esterase test, pyuria and a high number of bacteria. Empiric treatment with oral co-trimoxazole was started. Growth of small colonies of Gram-positive rods was observed after 48 h. Sequencing of the 16S rRNA gene confirmed an A. schaalii infection 9 days later. Treatment was changed to oral amoxicillin for 14 days. On follow-up urinalysis was normal and urine cultures were negative. Conclusions A.schaalii is an emerging pathogen in adults and children. Colonization and subsequent infection seem to be influenced by the age of the patient. In young children with high suspicion of UTI who use diapers or in children who have known abnormalities of their urogenital tract, infection with A. schaalii should be considered and empiric antimicrobial therapy chosen accordingly.

16S rRNA terminal restriction fragment length polymorphism for the characterization of the nasopharyngeal microbiota

A novel non-culture based 16S rRNA Terminal Restriction Fragment Length Polymorphism (T-RFLP) method using the restriction enzymes Tsp509I and Hpy166II was developed for the characterization of the nasopharyngeal microbiota and validated using recently published 454 pyrosequencing data. 16S rRNA gene T-RFLP for 153 clinical nasopharyngeal samples from infants with acute otitis media (AOM) revealed 5 Tsp509I and 6 Hpy166II terminal fragments (TFs) with a prevalence of >10%. Cloning and sequencing identified all TFs with a prevalence >6% allowing a sufficient description of bacterial community changes for the most important bacterial taxa. The conjugated 7-valent pneumococcal polysaccharide vaccine (PCV-7) and prior antibiotic exposure had significant effects on the bacterial composition in an additive main effects and multiplicative interaction model (AMMI) in concordance with the 16S rRNA 454 pyrosequencing data. In addition, the presented T-RFLP method is able to discriminate S. pneumoniae from other members of the Mitis group of streptococci, which therefore allows the identification of one of the most important human respiratory tract pathogens. This is usually not achieved by current high throughput sequencing protocols. In conclusion, the presented 16S rRNA gene T-RFLP method is a highly robust, easy to handle and a cheap alternative to the computationally demanding next-generation sequencing analysis. In case a lot of nasopharyngeal samples have to be characterized, it is suggested to first perform 16S rRNA T-RFLP and only use next generation sequencing if the T-RFLP nasopharyngeal patterns differ or show unknown TFs.

Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers

Chronic alcohol consumption is associated with an increased risk for upper aerodigestive tract cancer and hepatocellular carcinoma. Increased acetaldehyde production via alcohol dehydrogenase (ADH) has been implicated in the pathogenesis. The allele ADH1C*1 of ADH1C encodes for an enzyme with a high capacity to generate acetaldehyde. So far, the association between the ADH1C*1 allele and alcohol-related cancers among heavy drinkers is controversial. ADH1C genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism in a total of 818 patients with alcohol-associated esophageal (n=123), head and neck (n=84) and hepatocellular cancer (n=86) as well as in patients with alcoholic pancreatitis (n=117), alcoholic liver cirrhosis (n=217), combined liver cirrhosis and pancreatitis (n=17) and in alcoholics without gastrointestinal organ damage (n=174). The ADH1C*1 allele and genotype ADH1C*1/1 were significantly more frequent in patients with alcohol-related cancers than that in individuals with nonmalignant alcohol-related organ damage. Using multivariate analysis, ADH1C*1 allele frequency and rate of homozygosity were significantly associated with an increased risk for alcohol-related cancers (p<0.001 in all instances). The odds ratio for genotype ADH1C*1/1 regarding the development of esophageal, hepatocellular and head and neck cancer were 2.93 (CI, 1.84-4.67), 3.56 (CI, 1.33-9.53) and 2.2 (CI, 1.11-4.36), respectively. The data identify genotype ADH1C*1/1 as an independent risk factor for the development of alcohol-associated tumors among heavy drinkers, indicating a genetic predisposition of individuals carrying this genotype.