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Does Helicobacter pylori infection play a role in lung cancer?
Abstract
Helicobacter pylori infection is a world-wide common disease and leads to many gastrointestinal and respiratory illnesses. It is suggested that one of these respiratory illnesses is lung cancer.
Forty-three patients with non-small cell lung cancer and 28 control subjects have been included to this study. H. pylori status of the patients and controls was determined by immunoblot for the detection of IgG (RIDA Blot Helicobacter). All subjects were examined to evaluate the presence of VacA and CagA gene.
Seropositivity of anti H. pylori IgG was significantly higher in cancer patients than in control groups, 40 (93%) and 12 (42%), respectively (P<0.01). Although both VacA and CagA seropositivity was high in lung cancer patients, only VacA positivity was statistically significant when compared with control subjects, 35 (81%) and 11 (42%), respectively (P<0.05).
H. pylori infection may be associated with development of lung cancer.
... The others who are unable to produce these proteins are classified as Type II. Type I infections lead to a serious disorder (11). The International Agency for Research on Cancer classified HP as a group I carcinogenic agent (12). ...
... Lungs develop embryologically from the endodermal cells similar to the gastrointestinal tract and have similar cells producing several hormonal peptides (11). The increased plasma gastrin level associated with HP infection may contribute to pulmonary carcinogenesis via the introduction of the proliferation of bronchial mucosal cells (11). ...
... The relationship between HP seropositivity and lung cancer has been investigated in many studies. Ece et al. (11) found a 93% seroprevalence of antibodies against HP in 40 consecutive patients with lung cancer and a 42% seroprevalence in 12 control subjects. The results of the study by Behroozian and Moradkhans (1) showed that the population of patients with lung cancer has a significantly higher rate of seropositivity for antibodies against HP (48 of 66) than the population of subjects without lung cancer (34 of 66; OR=2.51, 95% CI=1.14-5.54; ...
Objective:Although the importance of environmental and occupational exposure to carcinogenic agents in pulmonary carcinoma is well known, some other factors, such as familial predisposition, genetic abnormalities, and recently, the presence of Helicobacter pylori infection, are being disputed. This study focused on the relationship between pulmonary carcinoma and H. pylori infection.Methods:In total, 48 histologically verified and operated patients with pulmonary carcinoma, including 38 males and 10 females, were included; 22 of the cases were of squamous cell carcinomas and 26 were adenocarcinomas. The control group composed of 20 patients who underwent pulmonary operation for causes other than lung cancer. Adjacent non-neoplastic parenchymal and bronchial tissue examples were stained using the Giemsa stain in carcinoma cases. The pulmonary tissue-contained bronchial sections were stained in control cases. The bronchial epithelia and lumina in the Giemsa stained slides were examined for H. pylori bacilli.Results:H. pylori was found in 2 of 48 carcinoma cases. The histopathological diagnosis of these 2 cases was squamous cell carcinoma. But there wasn't any case stained for H.pylori in the control group.Conclusion:The relationship between pulmonary carcinoma and H. pylori infection had been researched through serological studies; however, conflicting evidences have been obtained. The bacterium is transmitted to the lungs via seeding and inhalation was reported to be effective directly. Chronic H. pylori infection leads to bronchial epithelial proliferation via increased gastrin level and cyclo-oxygenase-2. Moreover, it contributes to pulmonary carcinogenesis. In conclusion, an association between H. pylori infection and pulmonary carcinoma may be revealed by variable studies, and the underlying mechanisms can be understood.
... However, evidence on H. pylori infection and risk of lung cancer has been controversial, with a limited number of underpowered studies that report result of increased risk [12][13][14], decreased risk [15], or no association [3,16,17] between the H. pylori infection and risk of lung cancer. This issue was discussed in previously conducted meta-analysis that analyzed the risk of lung cancer due to H. pylori infection by including 4 underpowered case-control studies published between 2000 and 2007 [18]. ...
... All studies assessed the H. pylori infection by Enzyme-Linked-Immuno sorbent Assay. Five studies histologically confirmed lung cancer [13][14][15][16][17], whereas one study assessed by checking the health register [3]. Only one study reported the subtype of lung cancer based on histology (lung adenocarcinoma and squamous cell carcinoma) [3]. ...
... . When the quality of the included studies was assessed, 1 high [3], 4 medium [14][15][16][17], and 2 low, quality studies were found [12,13] (Table 1). Cohort study had a NOS score of 7. With regard to casecontrol studies, only one study had NOS score of 9. Together case-control studies have an average NOS score of 8.4. ...
Background. Recent evidence showed that Helicobacter pylori seropositivity is a risk factor for gastric and several other cancers. However, evidence on H. pylori infection and risk of lung cancer has been controversial, with a limited number of underpowered studies. We therefore examined the association between H. pylori infection and risk of lung cancer. Methods. A comprehensive literature search was performed using PubMed, EMBASE (until October 2012) for studies investigating an association between Helicobacter pylori (H. pylori) infection and risk of lung cancer. Pooled odds ratio (OR) was calculated using random-effects model. Subgroup and sensitivity analysis were also done. Results. A total of seven studies (6 case-control and 1 cohort study) were included for the analysis. There was a significant heterogeneity among the studies, but no publication bias was observed. We found that H. pylori infection was associated with significantly increased risk of lung cancer (pooled OR, 2.29 (95% CI, 1.34–3.91) ). Conclusions. Our meta-analysis suggests a significant increased risk of lung cancer in patients with H. pylori infection. Further research is needed to confirm these findings and to identify the underlying biological mechanisms.
... One microbe postulated to play a role in lung cancer is Helicobacter pylori (H. pylori) [13,14]. H. pylori is a key etiologic agent in the development of distal stomach cancer [15]. ...
... With the observed inverse association between H. pylori and esophageal adenocarcinoma in Western countries and the lack of association with esophageal squamous cell carcinoma, an inverse association between H. pylori and lung adenocarcinoma but no association with lung squamous cell carcinoma also could be hypothesized. Prior assessment of the association between H. pylori and lung cancer has been limited, with fewer than 75 cases in each of five case-control studies [13,14,23,24,25]. A recent meta-analysis including four of these studies calculated a pooled odds ratio (OR) of 3.2 [95% confidence interval (CI): 1.1–9.5], ...
... The results of previous studies of H. pylori seropositivity and lung cancer have been mixed. Of the five previous small case-control studies, three found moderate to strong increased risk of lung cancer associated with H. pylori seropositivity [13,14,25], and two found only weak, non-statistically significant evidence of a positive association [23,24]. Two studies provided no information regarding smoking status and lung histology [14,23], and three provided limited information on smoking status [13,24,25]. ...
Lung cancer is the leading cause of cancer mortality worldwide. Helicobacter pylori (H. pylori) is a risk factor for distal stomach cancer, and a few small studies have suggested that H. pylori may be a potential risk factor for lung cancer. To test this hypothesis, we conducted a study of 350 lung adenocarcinoma cases, 350 squamous cell carcinoma cases, and 700 controls nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) cohort of male Finnish smokers. Controls were one-to-one matched by age and date of baseline serum draw. Using enzyme-linked immunosorbent assays to detect immunoglobulin G antibodies against H. pylori whole-cell and cytotoxin-associated gene (CagA) antigens, we calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between H. pylori seropositivity and lung cancer risk using conditional logistic regression. H. pylori seropositivity was detected in 79.7% of cases and 78.5% of controls. After adjusting for pack-years and cigarettes smoked per day, H. pylori seropositivity was not associated with either adenocarcinoma (OR: 1.1, 95% CI: 0.75-1.6) or squamous cell carcinoma (OR: 1.1, 95% CI: 0.77-1.7). Results were similar for CagA-negative and CagA-positive H. pylori seropositivity. Despite earlier small studies suggesting that H. pylori may contribute to lung carcinogenesis, H. pylori seropositivity does not appear to be associated with lung cancer.
... In animal models, H. pylori infection has been associated with morphological changes in lung tissues and increased inflammatory cytokines and endothelial dysfunction markers (13). However, epidemiological evidence on the association of H. pylori with lung cancer risk remains controversial and limited to a small sample size, retrospective or hospital-based design, and among smokers (14)(15)(16)(17)(18)(19). Two meta-analyses incorporating these epidemiologic studies have reported about 2-to 3-fold increased risk of lung cancer associated with H. pylori infection (20,21). ...
... Among heavy smokers, overall seropositivity of H. pylori was significantly associated with lung cancer risk. Our findings indicate that H. pylori (16), and 17.78 (14), but two other studies found suggestive but not statistically significant positive associations (15,17). A meta-analysis including all five aforementioned case-control studies summarized a 3.24fold increased lung cancer risk associated with H. pylori infection (21). ...
Helicobacter pylori (H. pylori) infection has been suggested to be associated with lung cancer risk. However, information is lacking on whether the association differs by H. pylori antigen. We conducted a nested case-control study within the Southern Community Cohort Study, including 295 incident lung cancer cases and 295 controls. H. pylori multiplex serology assay was performed to detect antibodies to 15 H. pylori proteins. Conditional logistic regression was used to estimate odds ratios (ORs) and confidence intervals (95% CIs) after adjustment for covariates. Overall H. pylori + was associated with a non-statistically significant increased risk of lung cancer (OR, 1.29; 95% CI, 0.85-1.95). Significant associations, however, were observed for H. pylori + VacA + (OR, 1.64; 95% CI, 1.02-2.62) and H. pylori + Catalase + (OR, 1.75; 95% CI, 1.11-2.77). The positive association of H. pylori + Catalase + with lung cancer risk was predominantly seen among African Americans (OR, 2.09; 95% CI, 1.11-3.95) but not European Americans (OR, 1.20; 95% CI, 0.56-2.54). Among participants who smoked ≥30 pack-years, overall H. pylori + (OR, 1.85; 95% CI, 1.02-3.35), H. pylori + CagA + (OR, 2.77; 95% CI, 1.35-5.70), H. pylori + VacA + (OR, 2.53; 95% CI, 1.25-5.13), and H. pylori + HP1564 + (OR, 2.01; 95% CI, 1.07-3.77) were associated with increased risk of lung cancer. Our study provides novel evidence that associations of H. pylori infection with lung cancer risk differ by H. pylori biomarker, may be more evident among African Americans, and may be modified by smoking habits. Further studies are warranted to confirm our findings.
... In contrast, alternative case-control investigations have demonstrated markedly elevated prevalence rates of seropositivity for antibodies targeting H. pylori among individuals afflicted with lung cancer, as compared to the control group [96][97]. ...
Abstracts Helicobacteriosis is a bacterial infection caused by Helicobacter pylori (H.pylori)(HP). which was discovered in
1982 by Australian scientists Barry Marshall and Robin Warren, who were later awarded the Nobel Prize in
2005.Epidemiological evidence has shown that H.pylori colonizes the upper gastrointestinal tract(GIT), and the infection is one
of the most common human bacterial pathogens worldwide, with 4.4 billion infected individuals in 2015, but the prevalence
varies according to situation and hygiene principles. Since this first isolation, it has become apparent that this organism may
be one of the most common bacterial pathogens of humans, and it is one of the risk factors for adenocarcinoma. Thus, it was
categorized as a group 1 carcinogen in 1994 by the World Health Organization (WHO). New infections with H.pylori are
thought to occur as a consequence of direct human-to-human transmission, via either an oral-oral or fecal-oral route or both.
H.pylori has been detected in stool, saliva, vomitus, and gastric refluxate, the material that has been subject to reflux,
principally stomach acid that has leaked up into the esophagus. Clinically, H. pylori infection in humans is related to chronic
gastritis, peptic ulceration, duodenal ulcer, and gastric cancer in addition to mucosa-associated lymphoid
malignancies.According to the World Health Organization (WHO) estimates available at that time, it was supposed that about
4.4 billion infected individuals in 2015 were infected with H. pylori. These estimations can vary and are subject to change over
time as recent investigations and information become obtainable. The prevalence of H. pylori is complex and affected by
several factors, comprising age, clinical outcomes, geographical location, and socioeconomic status. A higher incidence was
reported in unhygienic and economically poor areas; the rate of H. pylori infection in Africa, South America, and Asia was
significantly higher than that in Western Europe, North America, and Australia. However, the disease spectrum of H. pylori
infection shows a wide range of clinical aspects, including gastrointestinal diseases and extra gastric manifestations. In this
review, we have described the general scope of these diseases
... H. pylori infection may be related to the progression and treatment of lung cancer [43]. A retrospective study was conducted in two independent cohorts of PD-1-treated patients with non-small-cell lung cancer (NSCLC). ...
In recent years, the incidence of lung cancer is increasing. Lung cancer has become one of the most malignant tumors with the highest incidence in the world, which seriously affects people’s health. The most important cause of death of lung cancer is metastasis. Therefore, it is crucial to understand the mechanism of lung cancer progression and metastasis. This review article discusses the physiological functions, pathological states and disorders of the lung and intestine based on the concepts of traditional Chinese medicine (TCM), and analyzes the etiology and mechanisms of lung cancer formation from the perspective of TCM. From the theory of “the exterior and interior of the lung and gastrointestinal tract”, the theory of “the lung-intestinal axis” and the progression and metastasis of lung cancer, we proposed e “lung-gut co-treatment” therapy for lung cancer. This study provides ideas for studying the mechanism of lung cancer and the comprehensive alternative treatment for lung cancer patients.
... H. pylori has also been associated with many respiratory disorders, including COPD, bronchiectasis, asthma, tuberculosis, and lung cancer (42)(43)(44)(45)(46)(47)(48)(49). However, results from previous seroepidemiological studies were inconsistent (50)(51)(52)(53)(54)(55). Our data support the hypothetical role of H. pylori infection in ADC. ...
Background:
Computer Tomography (CT) screening can detect lung cancer early but suffers a high false positive rate. There is a need for molecular biomarkers that can distinguish malignant and benign indeterminate pulmonary nodules (IPN) detected by CT scan.
Methods:
We profiled antibodies against 901 individual microbial antigens from 27 bacteria and 29 viruses in sera from 127 lung adenocarcinoma (ADC), 123 smoker controls (SMC), 170 benign nodule controls (BNC) individuals using protein microarrays to identify ADC and BNC specific anti-microbial antibodies.
Results:
Analyzing 4th quartile odds ratios, we found more antibodies with higher prevalence in the 3 BNC subgroups than in ADC or SMC. We demonstrated that significantly more anti-Helicobacter pylori antibodies showed higher prevalence in ADC relative to SMC. We performed subgroup analysis and found that more antibodies with higher prevalence in light smokers (≤ 20 pack-years) compared with heavy smokers (> 20 pack-years), in BNC with nodule size > 1cm than in those with <= 1cm nodules, and in stage I ADC than in stage II and III ADC. We performed multivariate analysis and constructed antibody panels that can distinguish ADC vs. SMC and ADC vs. BNC with area under the receiver operating characteristics curve (AUC) of 0.88 and 0.80, respectively.
Conclusions:
Anti-microbial antibodies have the potential to reduce the false positive rate of CT screening and provide interesting insight in lung cancer development.
Impact:
Microbial infection plays an important role in lung cancer development and the formation of benign pulmonary nodules.
... Similar results were reported for CagA− and CagA+ H. pylori seropositivity [48]. On the other hand, other case-control studies revealed significantly higher rates of seropositivity for antibodies against H. pylori in patients with lung cancer than in controls [49][50][51]. A meta-analysis, published in 2013, included the above-mentioned studies and calculated the pooled OR [52]. ...
Helicobacter pylori (H. pylori) is a Gram-negative bacterium involved in the development of gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue. Unexplained iron deficiency anemia, idiopathic thrombocytopenic purpura and vitamin B12 deficiency have also been related to H. pylori infection, whereas for other extra-gastric diseases, the debate is still open. In this review, we evaluate and discuss the potential involvement of H. pylori infection in the pathogenesis of several respiratory diseases. A MEDLINE search of all studies published in English from 1965 to 2021 was carried out. Controversial findings have been reported in patients with bronchial asthma, chronic obstructive pulmonary disease, bronchiectasis, lung cancer, tuberculosis, cystic fibrosis, and sarcoidosis. Most of the available literature is concerned with case-control studies based on seroprevalence, with a small sample size and low consideration of confounders, which represents a potential issue. So far, there is no clear evidence of a causal association between H. pylori infection and respiratory diseases, and larger studies with appropriate epidemiological design are required.
... The gut microbiome has also been identified to play potential roles in the pathobiology of lung cancer. For example, H.pylori has been suggested to play a role in lung cancer pathology [412,413] with patients with lung cancer possibly having a significantly higher rate of seropositivity for antibodies against H.pylori [414], however these findings have not been well replicated [415,416]. The mechanisms behind bacterial burden and lung cancer include; the production of bacterio-toxins and proinflammatory factors, which could ultimately lead to the DNA damage and mutation causing malignancy, as well as a hyperinflammatory immune response [417,418]. ...
Nutritional immunity is the sequestration of bioavailable trace metals such as iron, zinc and copper by the host to limit pathogenicity by invading microorganisms. As one of the most conserved activities of the innate immune system, limiting the availability of free trace metals by cells of the immune system serves not only to conceal these vital nutrients from invading bacteria but also operates to tightly regulate host immune cell responses and function. In the setting of chronic lung disease, the regulation of trace metals by the host is often disrupted, leading to the altered availability of these nutrients to commensal and invading opportunistic pathogenic microbes. Similarly, alterations in the uptake, secretion, turnover and redox activity of these vitally important metals has significant repercussions for immune cell function including the response to and resolution of infection. This review will discuss the intricate role of nutritional immunity in host immune cells of the lung and how changes in this fundamental process as a result of chronic lung disease may alter the airway microbiome, disease progression and the response to infection.
... The lung cancer is a main health problem with a generally badPrognosis, during the last 50 years; its incidence is dramatically increasing,not only in men but also in women. It is one of the most common causes of mortality in the world (1,2), Lung cancer is the second most common cancer in both men and women. Most recent estimates of American Cancer Society reflect 160340 deaths due to lung cancer (87,750 in men and 72,590 in women), accounting for about 28% of all cancer deaths in United States (3). ...
Background: Helicobacter pylori is one of the most common bacterial Infections of humans affecting approximately 50% of the world's population, And leads to many gastrointestinal and respiratory diseases. One of the Respiratory diseases is lung cancer. Objectives: to show relationship between H Pylori infection and lung cancer histopathologically Methods: Sixty patients with lung cancer (34 patients with adenocarcinoma and 26 with squamous cell carcinoma) have been included to this study. All enrolled subjects underwent a15 minute, lateral flow immunoassay for the qualitative detection of IgG antibodies anti-H. Pylori in human serum (CTK Biotech, Inc USA) and a lateral immunochromatographic assay for the qualitative detection of H. Pylori antigen in human fecal specimen (CTK Biotech,Inc USA) , A p value of <0.05 was considered as significant. The statistical data analysis was performed with SPSS 22. Results: 60 lung cancer patients:(41)(68.4%) persons had H pylori Ab positive and (19)(31.6%) persons had Ab negative, while only(22)(36.6%) persons had H pylori Ag positive and(38)(63.4%) persons had Ag negative. From (34) adenocarcinoma patients there are (26)(76.4%) patients had H pylori Ab positive and only (8) (23.6%)had Ab negative. From (26) squamous cell carcinoma patients there are (15) (57.7%) had Ab positive and (11) (42.3%) had Ab negative. From (34) adenocarcinoma patients there are (15) (44.2%) adenocarcinoma patients had H pylori Ag positive and (19) (55.8%) had Ag negative. From (26) squamous cell carcinoma patients there are (7) (27%) of squamous cell carcinoma had Hpylori Ag positive and (19) (73%) had Ag negative. Conclusion: The results of this study shows that the patients with H. pylori seropositivity antibody was significantly higher than negativity in adenocarcinoma patients, while in squamous cell carcinoma H. pylori seropositivity antibody was slightly higher. And stool antigen negative patients higher than positive in both type of cancer.
... 57 Other authors found a significantly higher prevalence of H. pylori seropositivity in lung cancer patients than in controls. [58][59][60] On the contrary, a case-control study, conducted by Philippou et al., on a sample of 78 Greek patients with lung cancer compared with 68 controls, revealed no significant correlation between H. pylori infection and lung cancer. 61 similar findings have been reported by Najafizadeh et al. 62 A crucial question deals with possible pathogenic mechanisms through which the microrganism could be involved in the pathogenesis of lung cancer. ...
Helicobacter pylori (H. pylori) has been conclusively related to several gastroduodenal diseases. The possible role of the bacterium in the development of extragastric manifestations has been investigated in the past few years. To identify all publications on the association between H. pylori and respiratory diseases, a MEDLINE search of all studies published in English from 1965 to 2013 was conducted. All data are based on case-control studies. Controversial findings of H. pylori seroprevalence have been obtained in patients with bronchial asthma, lung cancer, pulmonary tuberculosis, sarcoidosis, cystic fibrosis, chronic bronchitis and bronchiectasis. At present, on epidemiological bases, there is no definite evidence of a causal relationship between H. pylori infection and respiratory diseases. There is a low consideration of confounding factors as poorer socioeconomic status and tobacco use. The activation of pro-inflammatory cytokines by H. pylori might be a possible pathogenetic mechanism. However, there are no convincing data about the influence of H. pylori on the inflammatory changes of the bronchoepithelium so far. Further studies are needed on the impact of H. pylori eradication, on the prevention, development and natural history of these disorders.
... Several studies suggest an inverse association between H. pylori colonization and risk of GE-Junction adenocarcinomas. [8][9][10][11] In addition, H. pylori colonization has been linked with reduced risks of asthma and allergy, [12][13] and the risks of cardiovascular diseases [14][15][16][17] and lung cancer [18][19][20][21][22][23] are uncertain, although studies vary in size and design. Since H. pylori has been related to risks of a variety of health outcomes, it is important to evaluate its influence on both total mortality and category-specific mortality. ...
Objective:
Persistent colonisation by Helicobacter pylori, and especially by cagA-positive strains, has been related to several health outcomes with effects in opposite directions. Thus, it is important to evaluate its influence on total and category-specific mortality.
Design:
We conducted prospective cohort analyses in a nationally representative sample of 9895 participants enrolled in the National Health and Nutrition Examination Survey III to assess the association of H pylori status with all-cause and cause-specific mortality. Analyses for the association of H pylori cagA positivity with mortality were conducted in 7384 subjects with data on H pylori cagA status.
Results:
In older people (> 40.1 years), H pylori was not associated with all-cause mortality (HR 1.00; 95% CI 0.84 to 1.18). There was an inverse association of H pylori status with stroke mortality (HR 0.69; 95% CI 0.44 to 1.08), and the inverse association was stronger for H pylori cagA positivity, with the HR of 0.45 (95% CI 0.27 to 0.76). H pylori was also strongly positively related to gastric cancer mortality. After we adjusted p values using the Benjamini-Hochberg false discovery rate method to account for multiple comparisons, these associations remained, and H pylori status was not related to other outcomes.
Conclusions:
Our findings suggest that H pylori has a mixed role in human health, but is not a major risk factor for all-cause mortality.
... A link with H. pylori infection has been sought in only four small case-control studies. Two studies reported a positive association (71,87), whereas the other two found no association. In the studies with null associations, there were no adjustments for important confounders such as smoking or sex (173,192). ...
Although scientific knowledge in viral oncology has exploded in the 20th century, the role of bacteria as mediators of oncogenesis has been less well elucidated. Understanding bacterial carcinogenesis has become increasingly important as a possible means of cancer prevention. This review summarizes clinical, epidemiological, and experimental evidence as well as possible mechanisms of bacterial induction of or protection from malignancy.
... Respiratory symptoms are major characteristics of inflammatory processes in the lungs, and inflammation plays a role in the pathogenesis of atherothrombosis (41,42). Further, it has been proposed that chronic inflammatory process in the lung may stimulate cell proliferation and growth, leading to lung cancer (43,44). ...
Respiratory symptoms are among the main reasons why patients make contact with healthcare professionals and they are associated with several diseases.
The aim of this study was to investigate the relationship between respiratory symptoms reported at one time and 30 years cause-specific mortality and incidence of lung cancer in an urban Norwegian population.
A total of 19 998 men and women, aged 15-70 years, were in 1972 selected from the general population of Oslo. They received a postal respiratory questionnaire (response rate 89%). All were followed for 30 years for end-point mortality and for lung cancer. The association between respiratory symptoms, given as a symptom load, and end point of interest were investigated separately for men and women by multivariable analyses, with adjustment for age, occupational exposure to air pollution and smoking habits.
A total of 6710 individuals died during follow-up. Obstructive lung diseases (OLDs) and pneumonia accounted for 250 and 293 of the total deaths, respectively. Ischaemic heart disease (IHD) accounted for 1572; stroke accounted for 653 of all deaths. Lung cancer developed in 352 persons during follow-up. The adjusted hazard ratio for mortality from OLD and pneumonia, IHD and stroke increased in a dose-response manner with symptom score, more strongly for OLD and IHD than for pneumonia and stroke.
Respiratory symptoms were positively associated with mortality from OLD, pneumonia, IHD and stroke, and incidence of lung cancer. This association was significant for mortality from OLD and IHD.
... Similarly, Ece et al [10] pointed out an association between H pylori infection and the risk of lung cancer. By comparing 43 patients with non-small cell carcinoma of the lung and 28 healthy controls selected from the patients' family members, they found that H pylori seroprevalence was statistically higher in cancer patients than in the control group (93% vs 42%, P < 0.05). ...
To assess Helicobacter pylori (H pylori) seroprevalence in a cohort of Greek patients with lung cancer.
Seventy-two lung cancer patients (55 males and 17 females, aged 58.2+/-11.7 years) and 68, age and gender-matched, control subjects were enrolled. All subjects underwent an enzyme-linked immunosorbent assay IgG serologic test for H pylori diagnosis.
A correlation between age and H pylori IgG level was detected for both lung cancer patients (r = 0.42, P = 0.004) and controls (r = 0.44, P = 0.004). Seropositivity for H pylori did not differ significantly between patients with lung cancer and controls (61.1% vs 55.9%, P>0.05). Concerning the mean serum concentration of IgG antibodies against H pylori, no significant difference between the two groups was detected (32.6+/-19.1 vs 27.4+/-18.3 U/mL, P>0.05).
No significant association between H pylori infection and lung cancer was found.
... 28 Ece and coworkers found a significantly higher frequency of HP seropositivity in lung cancer patients than in control subjects. [29][30][31] Philippou et al. 32 carried out a case-control study involving a sample of 78 Greek patients with lung cancer and 68 control subjects. Their data revealed no significant association between HP infection and lung cancer. ...
Helicobacter pylori (HP) infection may cause extradigestive manifestations directly or indirectly, by potential mechanisms. HP infection triggers a marked local inflammatory response and a chronic systemic immune response. Some of the mediators that are thought to be possibly involved in the pathogenesis of extradigestive diseases caused by HP infection include IL-1, TNF-alpha, interferon (IFN)-gamma, leukotriene C4 and platelet-activating factor. Previous epidemiological and serological case control studies have revealed that HP infection might have a role in the development of chronic bronchitis, bronchiectasis, lung cancer and tuberculosis. However HP infection does not appear to have a role in the development of bronchial asthma. Considering the importance and prevalence of respiratory system diseases, it may be time to conduct well-designed sets of studies to clarify whether there is an association with HP infection and respiratory system diseases, and to answer questions that have been posed regarding the patterns of histology, genotypes of HP, and the effects of eradication therapy. The aim of this review was to analyze the possible association between HP and respiratory disease and provide a critical review of the relevant literature.
... In one of these studies, the level of anti-H. pylori IgG was found higher in lung cancer patients than in the control group, whereas other studies did not find any significant differences between the groups (25,26). In addition, in other studies H. pylori seroprevalence was higher in patients with chronic obstructive pulmonary disease and chronic bronchitis than in the control group (27e29). ...
A number of studies have implicated an association between H. pylori and diverse extra-gastroduodenal pathologies. Chronic inflammation and increased immune response have been observed in bronchiectasis, likely gastroduodenal inflammatory diseases. H. pylori has been found in the trachea-bronchial aspirates of mechanically ventilated patients. Furthermore, the seroprevalence of H. pylori was found to be significantly higher in patients with bronchiectasis than in the control group. The present study was performed to investigate the possible role of H. pylori in the pathogenesis of bronchiectasis.
Prospectively, bronchoalveolar lavage fluid (BALF) was obtained from patients with bronchiectasis (n=26) and control (n=20). BALF was subjected to polymerase chain reaction (PCR) to determine the presence of H. pylori and serum IgG against H. pylori was determined with micro-ELISA kit. In addition, PCR was performed to determine H. pylori in surgically removed lung tissues from patients with bronchiectasis (n=97).
H. pylori DNA was not detected in the BALF or in lung tissue samples. In addition, anti-H. pylori IgG level in patients with bronchiectasis did not show statistically significant difference from that of the control.
Our study provided evidence that there might be no direct association between H. pylori and bronchiectasis; however, the indirect role of soluble products of H. pylori could not be excluded.
... Similarly, Ece et al [10] pointed out an association between H pylori infection and the risk of lung cancer. By comparing 43 patients with non-small cell carcinoma of the lung and 28 healthy controls selected from the patients' family members, they found that H pylori seroprevalence was statistically higher in cancer patients than in the control group (93% vs 42%, P < 0.05). ...
To assess H pylori seroprevalence in lung cancer and determine whether there is a potential association between lung cancer and H pylori infection.
The study was conducted on forty consecutive patients with lung cancer, confirmed by pathology (32 men, 8 women; mean age 55.50+/-11.91 years, range 16-77 years). Forty healthy subjects (25 men, 15 women; mean age 43.08+/-12.60 years, range 20-79 years) from the patients' family members were matched to each case subject on the basis of age and socioeconomic status. H pylori infection was detected with a commercially available immunoglobulin G (IgG) enzyme-linked immunosorbent assay (Trinity kit, Biotech co., USA), previously validated in adults (86% sensitivity, 96% specificity) against a gold standard of culture and histology.
H pylori seropositivity was present in 52.5% of patients with lung cancer in comparison to 45.0% of healthy control subjects. Although H pylori seropositivity was more frequent in lung cancer patients than in controls, the difference did not reach statistical significance (OR=1.35, 95% CI=0.56-3.25; P=0.65). In addition, there was no significant difference between cases and controls in terms of gastrointestinal symptoms.
The earlier described association between H pylori infection and lung cancer was not supported in this study. Further studies with larger sample sizes should be undertaken to assess the frequency of H pylori infection in patients with lung cancer and their potential association.
Identifying differentially expressed pathways (DEPs) plays important roles in understanding tumor etiology and promoting clinical treatment of cancer or other diseases. By assuming gene expression to be a sparse non-negative linear combination of hidden pathway signals, we propose a pathway crosstalk-based transcriptomics data analysis method (ctPath) for identifying differentially expressed pathways. Biologically, pathways of different functions work in concert at the systematic level. The proposed method interrogates the crosstalks between pathways and discovers hidden pathway signals by mapping high-dimensional transcriptomics data into a low-dimensional pathway space. The resulted pathway signals reflect the activity level of pathways after removing pathway crosstalk effect and allow a robust identification of DEPs from inherently complex and noisy transcriptomics data. CtPath can also correct incomplete and inaccurate pathway annotations which frequently occur in public repositories. Experimental results on both simulation data and real-world cancer data demonstrate the superior performance of ctPath over other popular approaches. R code for ctPath is available for non-commercial use at the URL http://micblab.iim.ac.cn/Download/.
It is well known that Helicobacter pylori infection is associated with gastroduodenal diseases such as gastritis, peptic ulcer diseases, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma (MALToma). Furthermore, various extra-gastroduodenal diseases have been suggested to be related with H. pylori infection. Although the exact pathophysiologic mechanisms have not been established yet, it is plausible that certain inflammatory and immune reactions triggered by H. pylori infection might play a role. In this review, I summarized the articles which dealt with H. pylori infection and extra-gastroduodenal diseases along with their pathophysiologic mechanisms.
Helicobacter pylori (H pylori) infection is one of the most common human infections worldwide. It is associated with the development of a number of important upper gastrointestinal (GI) diseases such as chronic gastritis, peptic ulcer and gastric malignancy. At present, there is evidence that H pylori infection probably plays a critical role in the development of some extragastric diseases. However, there is still controversy over such association. In this article, we will give an overview of the recent advances in understanding the association of H pylori infection with extragastric diseases.
The role of infectious agents such as bacteria, viruses, fungi etc. has been of interest for many years. Many studies have linked chronic bacterial infection with subsequent development of cancer at a number of different sites in the body.Most cancers have a multifactorial aetiology with a number of different steps between the normal and the malignant cell. One example of this is stomach cancer where it has been postulated that bacteria play a role at a number of stages but will also be true of cancers at other sites.This chapter summarises those situations where cancers occur as a possible result of bacterial infection and covers oesophageal, stomach, colorectal, gallbladder, pancreatic, bladder and lung cancer.
Helicobacter pylori (Hp) is one of the most common bacteria infecting humans. Recently, certain extragastric manifestations, linked to Hp infection, have been widely investigated, suggesting that Hp infection might be a "systemic" disease. Accumulating yet limited evidence points to a potential association between Hp infection and lung cancer risk. Epidemiologic studies have shown that odds ratios (estimated relative risks) of lung cancer with Hp infection range from 1.24 to 17.78 compared to the controls, suggesting an increased lung cancer risk in the population exposed to Hp infection although far from supporting a causal relationship between Hp and lung cancer. Many studies have demonstrated the existence of Hp in the mucosa of the upper respiratory tract with no direct evidence of Hp-localization in lung tissue in the published literatures, rendering the possible functional mechanism underlying the association an open question. We followed the classic hypothesis-generating path, where we have thoroughly reviewed the publications on lung cancer and Hp infection from serological association to possible mechanisms as: (1) p130cas activated by Src kinase following Hp-host communication and p130cas-related carcinogenesis as in various malignancies; and (2) gastroesophageal reflux and inhalation of urease or gastrin, which are Hp-related carcinogenic factors and present in lung tissues. We propose rigorous investigations regarding the Hp-lung cancer association and, if confirmed, the mechanisms of Hp infection leading to lung cancer development and progression. Clarification on Hp-lung cancer association is important for the understanding of lung cancer beyond tobacco-smoking-related carcinogenesis.
Helicobacter pylori (Hp) is the most common chronic bacterial infection in humans worldwide. The prevalence of Hp infection is high in developing countries (80-90%) and lower in developed countries (10-30%). In vast majority of infected individuals, the infection is acquired early in life. The risk of Hp infection is related to low socio-economic status and living conditions at early childhood (density of housing, overcrowding, number of siblings, sharing a bed, and lack of running water, low education of parents). Smoking is a risk factor of Hp infection in adults. In developed countries including the Czech Republic, the overall prevalence of Hp infection has fallen dramatically over recent decades. This decrease can be explained mostly by the relatively favourable and improving socio-economic conditions. However, it is necessary to consider also the fundamental determinants of "modern times" that could cause gradual disappearing of Hp from the human "microbiome".
Recent studies suggest an increased Helicobacter pylori prevalence in patients with various extradigestive inflammatory diseases. Similar to H. pylori infection, many respiratory diseases are characterized by chronic inflammation as well as increased immune response. Recent studies have evaluated the relation between various respiratory disorders and H. pylori infection. The aim of this systematic review was to scrutinize the relevant literature and the mechanisms that could underlie a role for H. pylori infection in respiratory diseases.
Relevant literature regarding pathophysiological mechanisms and clinical epidemiology of H. pylori and different respiratory diseases has been systematically identified and analyzed by two independent reviewers according to a PubMed search for English language (until week 14, April 2010).
At present, there is no definite proof of a causal relationship between H. pylori and respiratory diseases. Both H. pylori and various respiratory diseases are characterized by the release of proinflammatory cytokines and attraction of granulocytes as well as B- and T-cell-mediated response, though a pathophysiological association has not been proven. Neither the role of genetic predisposition of the host nor the presence of virulence factors nor the impact of H. pylori eradication have been studied in detail and definitely need further evaluation.
Helicobacter pylori proteins CagA (cytotoxin-associated gene A) and VacA (vacuolating cytotoxin A) are among the virulence factors of this species. CagA gene carrying H. pylori strains are particularly associated with gastric adenocarsinoma. This study was conducted to evaluate Western Blot (WB) method to determine specific H. pylori antibodies in a group of patients with gastric cancer and in a control group with no malignancy. A total of 99 patients with gastric cancer (94 adenocarcinoma, 2 adenosquamous cell carcinoma, 3 non-Hodgkin lymphoma) and 150 control cases with epigastric complaints such as nausea, vomiting, diarrhea, gastroesophageal reflux and abdominal pain, were included to the study. H. pylori IgG-ELISA was positive in all study (mean age: 56.7 +/- 1.2 years, 62 male) and control (mean age: 24.2 +/- 1.3 years, 64 male) patients. Specific antibodies against CagA, VacA, OMP (outer membrane protein)-67, urease-A, urease-B, HSP (heat shock protein) and flagellin antigens determined by a commercial WB-based kit (RIDA Blot Helicobacter, R-Biopharm GmbH, Germany). Interestingly, no anti-VacA positivity was detected in none of the patient and control groups. The positivity rates for H. pylori CagA, OMP-67, urease A, urease-B, flagellin and HSP specific antibodies were as 78%, 54%, 37%, 60%, 53% and 82% in the gastric cancer group and 85%, 71%, 55%, 43%, 61% and 75% in the control group, respectively. There was no statistically significant difference (p > 0.05) between gastric carcinoma and control groups in terms of CagA, HSP and flagellin antibodies (p > 0.05). On the other hand, a statistically significant difference was found between the 2 groups in terms of urease-A, urease-B and OMP-67 (p < 0.01). These results suggested that this test should be assessed again by the manufacturer for its detection power directed towards specific H. pylori antibodies, especially for Vac-A. Further molecular and clinical studies are necessary to determine the factors that affect H. pylori virulence and disease prognosis.
Helicobacter pylori infection has been thought to play a critical role in gastric carcinoma tumorigenesis and progression. Several studies have been devoted to the relationship between H. pylori infection and lung cancer risk and have generated inconclusive results. In this study we aimed to evaluate the potential association of H. pylori infection with lung cancer risk.
We conducted a search in Medline, OVID, EMBASE and CNKI, covering all published papers until October 2008. The relevant published papers were deliberately selected according to the established inclusion criteria for publications. Essential data were then extracted from the included studies and further analyzed by a systematic meta-analysis.
A total of 98 papers were identified. Of these, four case-control studies met the inclusion criteria and thus were finally selected. Lung cancer risk for H. pylori infection was 3.24-fold (95% CI=1.11-9.47) (Z=2.15, p<0.05) compared with the controls.
The pooled data suggest infection of H. pylori as a potential risk factor for lung cancer.
Gene ranking problem in time course microarray experiments is challenging since gene expression levels between different time points are correlated. This is because, expression values at successive time points are usually taken from the same organism, tissue or culture. Moreover, time dependency of gene expression values is usually of interest and often is the biological problem that motivates the experiment. We propose a multivariate growth curve model for ranking genes and estimating mean gene expression profiles in replicated time course microarray data. The approach takes the within individual correlation as well as the temporal ordering into consideration. Moreover, time is incorporated as a continuous variable in the model to account for the temporal pattern. Polynomial profiles are assumed to describe the time dependence and a transformation incorporating information across the genes is used. A moderated likelihood ratio test is then applied to the transformed data to get a statistic for ranking genes according to the difference in expression profiles among biological groups. The methodology is presented in a general setup and could be used for one sample as well as more than one sample problem. The estimation is done in a multivariate framework in which information from all the groups involved is used for better inference. Moreover, the within individual correlation as well as information across genes entered in the estimation through a moderated covariance matrix. We assess the performance of our method using simulation studies and illustrate the results with publicly available real time course microarray data.
Because aggregation of cancers at different sites can occur in families, cancer could be considered as a broad phenotype with shared genetic factors. Here, we report results from a multi-centre case-control study of non-small cell lung cancer (NSCLC), with particular emphasis on a history of cancer in first-degree relatives and the risk of lung cancer. From 2002 to 2006, 733 NSCLC patients treated surgically were recruited in 8 European countries and matched to 1312 controls, by centre, sex and age. We used multivariate conditional logistic regression models to test the association between a history of cancer in first-degree relatives and risk of NSCLC. A family history of lung cancer was associated with an odds ratio (OR) for early-onset (54 years or younger) NSCLC of 4.72 (95% confidence interval [CI]=1.02-21.90). A family history of gastric cancer was associated with an OR for NSCLC of 1.82 (95% CI=1.08-3.06) and for late-onset (55 years or older) NSCLC of 2.92 (95% CI=1.10-7.75). Our findings provide further evidence of a familial predisposition to lung cancer and support the hypothesis that family history is a significant risk factor for the disease. Because of the inherent potential for bias in familial case-control study design, cautious interpretation is warranted.
Recent studies suggest an epidemiological association between Helicobacter pylori infection and several extra-gastroduodenal pathologies, including cardiovascular, rheumatic, skin and liver diseases. The observed associations might be explained by a role of H. pylori infection in the pathogenesis of certain extra-digestive disorders, as a variety of inflammatory mediators are activated by H. pylori infection. The present review summarizes the current literature, including our own studies, concerning the association between respiratory diseases and H. pylori infection. A small number of epidemiological and serologic case-control studies suggest that patients with chronic obstructive pulmonary disease have an increased seroprevalence of H. pylori. A frequent coexistence of bronchiectasis and H. pylori infection has also been found. Moreover, recent studies have shown an increased prevalence of H. pylori infection in patients with pulmonary tuberculosis and in those with lung cancer. On the other hand, bronchial asthma does not seem to be related to H. pylori infection. At present, there is no definite proof of a causal relationship between H. pylori and respiratory diseases. The primary evidence rests on case-control studies, concerning relatively small numbers of patients. Future studies should be large enough for moderate-sized effects to be assessed or registered reliably. The activation of inflammatory mediators by H. pylori infection might be the pathogenetic mechanism underlying the observed associations. Therefore, the role of genetic predisposition of the infected host, the presence of strain-specific virulence factors and the serum concentration of proinflammatory markers in H. pylori-infected patients with respiratory diseases need further evaluation.
Even though Helicobacter pylori infection is an obvious cause of chronic non-atrophic and atrophic gastritis, as well as gastric dysplasia and cancer, several recent controlled intervention trials for the prevention of gastric cancer by H. pylori eradication have yielded disappointing results. They showed that cancer eradication may still appear in relatively high frequency after successful treatment of H. pylori. One explanation for this observation is that H. pylori treatment has less influence in development of gastric cancer in atrophic gastritis than in development of cancers in non-atrophic gastritis, and that eradication does not prevent the progression of precancerous lesions and small invisible early cancers to overt tumors. Noteworthy however, the available intervention trials show that gastric cancer can be prevented by H. pylori treatment in patients with non-atrophic gastritis. Trials with higher number of patients, with longer follow-up periods, and with more careful controlling of cancer type and underlying gastric mucosal conditions are needed.
Recent studies have indicated a strong link between Helicobacter pylori and idiopathic thrombocytopenic purpura and iron deficiency anemia. Interesting results have also been obtained for ischemic heart disease, though most putative associations between H. pylori infection and extragastric disease remain speculative. With regard to other Helicobacter species, Helicobacter felis has been shown to play a role in gastric carcinogenesis in mouse models. An increased susceptibility to cholesterol gallstone formation has been described in animals fed a lithogenic diet and infected with Helicobacter bilis, or co-infected with Helicobacter hepaticus and Helicobacter rodentium. Finally, enterohepatic Helicobacter species have also been exploited to better understand inflammatory bowel disease.
This review summarizes the literature on Helicobacter pylori infection in childhood between April 2005 and March 2006, and includes guidelines of the Canadian Helicobacter Study Group Consensus Conference, noninvasive tests, optimum therapy regimens and problems with resistance, and reviews on immune mechanisms in the gastric mucosa that may lead to the development of an effective vaccine.
In clinical practice the recommended treatment regimens achieve only an 80%Helicobacter pylori eradication rate and this rate is lower in patients who have failed first-line treatment. The increasing indications for H. pylori treatment (idiopathic thrombocytopenia and iron deficiency anemia) and an increasing trend of antibiotic resistance (especially in southern Europe) emphasize the need for more effective H. pylori eradication. Smoking and a short duration of treatment, especially in patients with functional dyspepsia, are predictors of eradication failure. In first line, the best option remains the clarithromycin-based regimens but an extended treatment duration is now indicated. Following first-line treatment failure, 14-day proton pump inhibitor triple therapy employing alternative antibiotics or quadruple therapy could be used. Levofloxacin-based 10-day triple therapy seems to be an encouraging strategy following one or more eradication failures.
Important new data were published during the past year on the relationship of Helicobacter infection and gastric neoplasias. In the pathogenesis of gastric cancer, a thrilling new hypothesis was put forward based on animal experiments. Helicobacter infection induces gastric mucosal damage and bone marrow-derived cells (mobilized into peripheral blood and attracted to the inflamed mucosa) replace the areas of damaged gastric tissue and turn into neoplastic proliferation. Several studies focused on mechanisms related to the development of gastric malignancy in infected individuals with particular attention to inflammatory cytokine gene polymorphisms.
Some new evidence is also reported to suggest that Helicobacter infection increases the risk of neoplasias outside the stomach in the liver and colon.
The prevalence of Helicobacter pylori-associated peptic ulcers, in particular duodenal ulcers, is decreasing following decreasing prevalence of H. pylori infection, while the frequency of non-steroidal anti-inflammatory drugs (NSAIDs)-induced and H. pylori-negative idiopathic ulcers is increasing. The incidence of bleeding ulcers has been stable during the last decades. Several putative H. pylori virulence genes, i.e., cag, vacA, babA, or dupA, as well as host-related genetic factors like IL-1beta and TNFalpha-gene polymorphism, have been proposed as risk factors for duodenal ulcer. H. pylori eradication may prevent NSAID complications, in particular, when it is performed before introduction of NSAIDs. There is a complex association between H. pylori and gastroesophageal reflux disease (GERD), and the impact of H. pylori eradication on the appearance of GERD symptoms depends on various host- and bacteria-related factors. Eradication of H. pylori in GERD is recommended in patients before instauration of a long-term PPI treatment to prevent the development of gastric atrophy. A small proportion (10%) of non-ulcer dyspepsia cases may be attributed to H. pylori and may benefit from eradication treatment. A test-and-treat strategy is more cost-effective than prompt endoscopy in the initial management of dyspepsia.
The reason why some individuals remain Helicobacter pylori infected for life but without any symptoms while others develop severe diseases is only partially clarified. Presumably, it depends on multifactorial interactions among host immunologic and physiologic factors, bacterial virulence determinants, and environmental influences modulating the host response. Much effort has been made to identify host genetic factors that may explain an individual susceptibility of the host to H. pylori infection. The identification of H. pylori determinants and the elucidation of their role in modifying the host immune responses were further delineated. The ability of H. pylori to overcome the defense mechanisms on mucosal surfaces as well as to modulate the immune response by interfering with host recognition and transduction systems has been shown. Also new bacterial anti-inflammatory defense systems have been described. Findings in experimental animal models and humans with natural H. pylori infection suggested a double role of regulatory T cells in the course of H. pylori infection: protecting the infected host against excessive gastric inflammation and, in contrast, promoting bacterial colonization.
Much interest has been shown in the relationship between Helicobacter pylori infection and gastric carcinogenesis. It is becoming clearer that H. pylori strains carrying a functional cag pathogenicity island (cagPAI), which encodes the type IV secretion system (TFSS) and its effector CagA, play an important role in the development of gastric carcinoma. Furthermore, genetic polymorphism present in the cagA gene appears to influence the degree of an individual cagPAI-positive H. pylori to elicit gastric mucosal lesions, and this process is significantly affected by host genetic polymorphisms such as proinflammatory cytokine gene polymorphisms. Pathomechanism of gastric carcinogenesis associated with H. pylori includes bacteria-host interaction leading to morphologic alterations such as atrophic gastritis and gastrointestinal metaplasia mediated by COX-2 overexpression, cancer cell invasion, and neo-angiogenesis via TLR2/TLR9 system and transcription factors (e.g., NF-kappaB) activation. In addition, H. pylori infection triggers adhesion molecule expression and activity and produces an enhancement in oxidative stress interacting with gastric production of appetite hormone ghrelin and nonsteroidal anti-inflammatory drugs.
Differences may occur in the mode of transmission of Helicobacter pylori between developed and developing countries: direct human-to-human contacts have been suggested as the primary route in the former while the fecal-oral route, also, through contaminated water, in the latter. Data on intrafamilial transmission of H. pylori among children continue to be produced. The importance of low socioeconomic conditions on the acquisition of H. pylori infection has been confirmed in a number of population-based studies. Due to the improvement of living standards, the prevalence of the infection has fallen dramatically in many countries. It varies from 8.9 to 72.8% among children from developed and developing countries, respectively, the re-infection rate being also significantly higher in the latter. Conflicting data have been reported on the effect of breastfeeding against H. pylori colonization in infancy as well as on the occupational risk for acquiring H. pylori. This review summarizes recent results from the literature on these topics.
Lung cancer is the most common cause of cancer death in the world. It continues to have an enormous impact on health systems of all countries. The number of new cases is increasing in a rate of about 3% annually. Despite the advances in the detection and treatment of lung cancer, the overall 5-year survival still remains grim. Cigarette smoking remains the major risk factor on the incidence of cancer, with 90% of all lung cancers occurring in smokers. The frequency of different types of lung cancer is changing. Adenocarcinoma has become the most frequent histologic type (approximately 50%) while squamous, previously the most common, accounts for approximately one third of lung cancers, and small cell cancer for 15%. Prognosis is influenced by the stage of the disease at diagnosis and by the treatment. Screening trials that have begun in the early 1950s based on chest X-ray and sputum cytology did not produce improvement in overall mortality. Refinements in the staging classification of lung cancer and advances in stage identification were introduced in the 1990s. Post surgical mortality has declined since the 1950s but the 5-year survival rates have improved only minimally. A gradual improvement is seen in locally advanced inoperable non-small cell lung cancer, mainly due to addition of advanced chemotherapy and radical radiotherapy. Chemotherapy offers small improvement for patients with NSCLC. The management of small cell lung cancer, which appeared so promising in the 1970s has hit a plateau with vary little advance in the last years. The biological active agents currently in phase III trails offer some hope in the advance of therapy of lung cancer. The most important and cost-effective management for lung cancer is smoking cessation, but for those with this disease novel methods of treatment are urgently needed.
To briefly review previously published evidence for Helicobacter pylori (Hp), colonization of extra-intestinal sites and suggest an hypothesis that breast acini and ducts be added to this list, concluding such breast colonization is not rare and is a sexually transmitted infection.
PubMed literature search and review with a case report.
(1) Evidence indicates oral Hp is common and can remain in the mouth after successful eradication in stomach and duodenum. (2) Evidence indicates that the breast is also occasionally colonized by Hp. (3) Hp may be injected retrograde up into ducts of the breast during oral nipple stimulation during sexual activity and this Hp may give rise to some cases of fibrocystic breast change. (4) A case of painful fibrocystic change that had been present for two years in a 27 year old female, resolved after gastrointestinal Hp treatment.
Since the discovery of Helicobacter pylori, several studies have investigated the hypothetical role of this bacterium in various extragastric diseases, e.g. ischemic heart disease, idiopathic thrombocytopenic purpura, iron-deficiency anaemia, and other disorders. The majority of these studies are epidemiological or eradication trials, but there are also case reports and in-vitro studies. Idiopathic thromobocytopenic purpura is the disease that shows the strongest link with H. pylori infection. There is also evidence of a role of CagA-positive H. pylori infection in iron-deficiency anaemia and ischemic heart disease. The association between H. pylori infection and other extragastric diseases remains controversial, being mostly supported by 'case reports', small pilot studies, or just in-vitro data. Further studies are needed to identify whether there is any pathological implication for H. pylori infection in these diseases.
BioArena as a complex bioautographic system was successfully used for studying mechanism of action of some characteristic plant ingredients (e.g., 1'-methyl-ascorbigen, trans-resveratrol, salicylic acid, cinnamic acid). It has been established that the formaldehyde as a main component of formaldehyde cycle and other biochemical pathways can be studied in chromatographic spots as well. Ozone as a specially reactive reaction product of formaldehyde can be measured indirectly there. Different formaldehyde-capturing and -giving molecules and other compounds influenced (inhibited or promoted) characteristically the antibiotic effect.
We investigated the relationship between respiratory symptoms reported at one time and incidence of lung cancer the subsequent 30 years in an urban Norwegian population. A cohort of 19,998 persons, aged 15-70 years living in Oslo, was randomly selected for a respiratory survey in 1972. The response-rate was 89% and 17,670 respondents were followed up. The relationship between respiratory symptoms and lung cancer incidence was investigated separately for each symptom group, symptom score and sex, with adjustment for age, smoking habits and occupational exposure. Lung cancer developed in 352 persons (228 men and 124 women) during follow up. We found a significant positive association between the incidence of lung cancer and cough symptoms in both sexes, asthma-like symptoms among women and dyspnoea when walking uphill among men. The relative risk for lung cancer increased with the number of symptoms reported at baseline and was strongest the first decade and decreased with duration of follow up. This association was more pronounced for non-small cell lung cancer than for small cell lung cancer.
Vocal nodules and polyps are two common noninfectious causes of hoarseness. Patients with persistent hoarseness often require microscopic laryngeal surgery to excise mass lesions of the larynx despite extensive voice resting and modification of voice use behavior. Helicobacter pylori has recently been reported to present in the upper aerodigestive tract. This study applies the rapid urease test to determine the colonization of Helicobacter pylori in surgical specimens of patients with vocal nodules and polyps.
In this prospective study, 53 consecutive patients with vocal nodules (n = 20) or vocal polyps (n = 33) were investigated from November 2004 to July 2005. Microscopic laryngeal surgery was performed in all cases. Tissue specimens harvested from the larynx were analyzed using the rapid urease test.
The study population consisted of 33 females and 20 males with a mean age of 43.1 +/- 9.9 years. Thirteen (24.5%) of the 53 patients revealed Helicobacter pylori colonization, and all were histopathologically diagnosed with vocal polyps. The difference in incidence of Helicobacter pylori colonization between vocal nodules and vocal polyps was statistically significant (0% [0/20] vs. 39.4% [13/33], P = .001).
Helicobacter pylori often colonizes in the larynxes of patients with vocal polyps. These results indicate the involvement of Helicobacter pylori in vocal polyps. However, the presence of Helicobacter pylori as an etiologic factor in vocal polyps remains inconclusive.
AIM: To follow the principles of evidence based medicine to reach the integrated results of these studies.
METHODS: Twenty-one papers of case-control studies were selected, including 11 on gastric cancer, 7 on precancerous lesion of stomach and 3 on lymphoma of stomach. Meta analysis was used to sum up the odds ratios (OR) of these studies.
RESULTS: H. pylori vsgastric cancer (intestinal and diffuse type): the odds ratio from the fixed effect model is 3.0016 (95% CI: 2.4197-3.7234, P < 0.001). H. pylori vs precancerous lesion of stomach: a random effect model was used to calculate the summary odds ratio and its value is 2.5635 (95% CI: 1.8477-3.5566, P < 0.01). H. pylori vs lymphoma of stomach: though the quantity of literature is too small to make Meta analysis, the data of these 3 studies show that lymphoma of stomach is highly associated with H. pylori infections.
CONCLUSION: Since it had been revealed that H. pylori infection pre-exists in gastric carcinoma and precancerous lesions, the results of Meta analysis present a strong evidence to support the conclusion that H. pylori infection is a risk factor for gastric carcinoma.
Using a library of radioimmunoassays against essential sequences of human progastrin and procholecystokinin, we have examined the occurrence of gastrin, cholecystokinin, and their precursors in bronchogenic adenocarcinomas, large-cell, small-cell, and squamous-cell carcinomas (n = 17). Progastrin and some of its bioactive (i.e., alpha-carboxyamidated) products were present in all tumors, irrespective of histological classification. The concentration of progastrin varied from 0.2 to 21.9 pmol/g tissue; glycine-extended intermediates constituted less than 0.1 to 0.5 pmol/g; and bioactive, carboxyamidated gastrin ranged from less than 0.1 to 6.1 pmol/g. Chromatography showed that the bioactive gastrins were exclusively gastrin-17 peptides, half of which were tyrosine O-sulfated. Neither procholecystokinin nor its processing products were found in the tumor extracts. Six samples of nonneoplastic human lung tissue contained traces of progastrin (range, less than 0.1-0.8 pmol/g), but neither bioactive gastrins nor any cholecystokinin. The results show that the gastrin gene is expressed in all classes of bronchogenic carcinomas. Due to incomplete posttranslational processing measurement of progastrin may be necessary to detect such expression.
Helicobacter pylori has been associated with gastritis, peptic ulcer, and gastric adenocarcinoma. We report the nucleotide sequence and expression of an immunodominant antigen of H. pylori and the immune response to the antigen during disease. The antigen, named CagA (cytotoxin-associated gene A), is a hydrophilic, surface-exposed protein of 128 kDa produced by most clinical isolates. The size of the cagA gene and its protein varies in different strains by a mechanism that involves duplication of regions within the gene. Clinical isolates that do not produce the antigen do not have the gene and are unable to produce an active vacuolating cytotoxin. An ELISA to detect the immune response against a recombinant fragment of this protein detects 75.3% of patients with gastroduodenal diseases and 100% of patients with duodenal ulcer (P < 0.0005), suggesting that only bacteria harboring this protein are associated with disease.
The gastrin gene is known to be expressed in all classes of bronchogenic carcinomas. Furthermore, high levels of gastrin have been reported in both the bronchoalveolar lavage (BAL) fluid and serum of patients with lung cancer. Based on these preliminary data a study was conducted to evaluate the usefulness of gastrin measurements in the diagnosis and staging of lung cancer.
Thirty-five patients with lung cancer (26 non-small cell (NSCLC) and nine small cell (SCLC)) and 25 patients with chronic obstructive pulmonary disease underwent fibreoptic bronchoscopy and BAL. Gastrin levels were determined in both BAL fluid and the serum and compared with each other and with staging.
No difference was found between the gastrin levels in the BAL fluid or serum of the study groups. There was no correlation with the stage in NSCLC and no correlation was found between the gastrin levels in the serum and the BAL fluid. A significant difference was seen in gastrin levels in BAL fluid between extensive and limited SCLC (p < 0.05).
There is no evidence of clinical usefulness for gastrin measurements in lung cancer.
To follow the principles of evidence based medicine to reach the integrated results of these studies.
Twenty-one papers of case-control studies were selected, including 11 on gastric cancer,7 on precancerous lesion of stomach and 3 on lymphoma of stomach. Meta analysis was used to sum up the odds ratios (OR) of these studies.
H. pylori vs gastric cancer (intestinal and diffuse type): the odds ratio from the fixed effect model is 3.0016 (95% CI: 2.4197-3.7234, P<0.001). H. pylori vs precancerous lesion of stomach: a random effect model was used to calculate the summary odds ratio and its value is 2.5635 (95% CI: 1.8477-3.5566, P<0.01). H. pylori vs lymphoma of stomach: though the quantity of literature is too small to make Meta analysis, the data of these 3 studies show that lymphoma of stomach is highly associated with H. pylori infections.
Since it had been revealed that H. pylori infection pre-exists in gastric carcinoma and precancerous lesions, the results of Meta analysis present a strong evidence to support the conclusion that H. pylori infection is a risk factor for gastric carcinoma.
In the past few years, a variety of extradigestive disorders, including cardiovascular, skin, rheumatic and liver diseases, have been associated with Helicobacter pylori (H. pylori) infection. The activation of inflammatory mediators by H. pylori seems to be the pathogenetic mechanism underlying the observed associations. The present review summarizes the current literature, including our own studies, concerning the association between H. pylori infection and respiratory diseases. A small number of epidemiological and serologic, case-control studies suggest that H. pylori infection may be associated with the development of chronic bronchitis. A frequent coexistence of pulmonary tuberculosis and H. pylori infection has also been found. Moreover, recent studies have shown an increased H. pylori seroprevalence in patients with bronchiectasis and in those with lung cancer. On the other hand, bronchial asthma seems not to be related with H. pylori infection. All associations between H. pylori infection and respiratory diseases are primarily based on case-control studies, concerning relatively small numbers of patients. Moreover, there is a lack of studies focused on the pathogenetic link between respiratory diseases and H. pylori infection. Therefore, we believe that larger studies should be undertaken to confirm the observed results and to clarify the underlying pathogenetic mechanisms.
The mostly known genotypic virulence features of H. pylori are cytotoxin associated gene A (cagA) and Vacuoliting cytotoxin gene A (VacA). We investigated the association of these major virulence factors with ulcer and non-ulcer dyspepsia in our region.
One hundred and forty two dyspeptic patients were studied (average age 44.8+/-15.9 years, range 15-87 years, 64 males and 78 females). Antral and corpus biopsies were taken for detecting and genotyping of H. pylori. 107 patients who were H. pylori positive by histological assessment were divided into three groups according to endoscopic findings: Duodenal ulcer (DU), gastric ulcer (GU) and non-ulcer dyspepsia (NUD). The polymerase chain reaction (PCR) was used to detect CagA and VacA genes of H. pylori using specific primers.
H. pylori was isolated from 75.4 % (107/142) of the patients. Of the 107 patients, 66 (61.7 %) were cagA-positive and 82 (76.6 %) were VacA-positive. CagA gene was positively associated with DU and GU (P<0.01, P<0.02), but not with NUD (P>0.05). Although VacA positivity in ulcer patients was higher than that in NUD group, the difference was not statistically significant (P>0.05).
There is a significantly positive association between CagA genes and DU and GU. The presence of VacA is not a predictive marker for DU, GU, and NUD in our patients.
To assess Helicobacter pylori (H pylori) seroprevalence in a cohort of Greek patients with lung cancer.
Seventy-two lung cancer patients (55 males and 17 females, aged 58.2+/-11.7 years) and 68, age and gender-matched, control subjects were enrolled. All subjects underwent an enzyme-linked immunosorbent assay IgG serologic test for H pylori diagnosis.
A correlation between age and H pylori IgG level was detected for both lung cancer patients (r = 0.42, P = 0.004) and controls (r = 0.44, P = 0.004). Seropositivity for H pylori did not differ significantly between patients with lung cancer and controls (61.1% vs 55.9%, P>0.05). Concerning the mean serum concentration of IgG antibodies against H pylori, no significant difference between the two groups was detected (32.6+/-19.1 vs 27.4+/-18.3 U/mL, P>0.05).
No significant association between H pylori infection and lung cancer was found.
For the past decade, cellular oncogenes have attracted the attention of biologists intent on understanding the molecular origins of cancer. As the present decade unfolds, oncogenes are yielding their place at center stage to a second group of actors, the tumor suppressor genes, which promise to teach us equally important lessons about the molecular mechanisms of cancer pathogenesis.
The human gastric bacterial pathogen Helicobacter pylori has been implicated in type B gastritis, peptic ulceration and gastric adenocarcinoma. Here we report on the cloning and genetic characterization of an H. pylori gene named vacA, which encodes the vacuolating cytotoxin VacA, a novel type of antigenic bacterial toxin that induces the formation of intracellular vacuoles in epithelial cells. The vacuolating cytotoxin activity is expressed by a subset of clinical isolates (Vac+), all of which produce the 87kDa cytotoxin antigen, but strains which produce neither the activity nor the cytotoxin protein (Vac−) also carry the gene, Isogenic H. pylori mutants in vacA generated by transposon shuttle mutagenesis produce neither the VacA antigen nor a vacuolating activity in a cell culture model. The vacA gene itself encodes a precursor protein of 139.6 kDa consisting of a 33-amino acid signal sequence, the 87 kDa cytotoxin and a 50 kDa C-termlnal domain with features typical of a bacterial outer membrane protein. The VacA precursor shows no significant primary sequence homology with any previously reported protein, but its structural organization closely resembles the IgA protease-type of exoprotein produced by pathogenic Neisseriae and Haemophilus species. Our current data support a model for secretion of the cytotoxin through the two bacterial membranes which involves the 50 kDa domain for outer membrane translocation with subsequent proteolytic cleavage and release of the mature 87 kDa cytotoxin into the extracellular environment.
Serial changes in serum gastrin level were detected by radioimmunoassay in 58 lung cancer patients before and after operation. In comparing these tests with those of 40 cases of noncancerous thoracic lesions and 151 normal adults, the serum gastrin from lung cancer patients is significantly higher than that of noncancerous thoracic lesions and normal individuals (P less than 0.01). The gastrin level is closely related to stage of cancer, size of primary tumor, presence of lymph node metastasis, and type of histological classification. The serum gastrin was found to decrease gradually after the removal of the tumor and to return to normal on the 14th postoperative day. Those patients whose serum gastrin level can return to normal on the 14th postoperative day will have a good prognosis; if not, their prognosis will be very poor. These results suggest that serum from patients with lung cancer contains a high concentration of gastrin that can help differentiate benign from malignant thoracic lesions and evaluate prognosis of patients with lung cancer. Therefore, the cause of high serum gastrin in patients with lung cancer is likely due to the gastrin-producing property of the lung cancer cells.
For the past decade, cellular oncogenes have attracted the attention of biologists intent on understanding the molecular origins of cancer. As the present decade unfolds, oncogenes are yielding their place at center stage to a second group of actors, the tumor suppressor genes, which promise to teach us equally important lessons about the molecular mechanisms of cancer pathogenesis.
Segregation analyses that allowed for variable age of onset of lung cancer and smoking history were performed on 337 families, each ascertained through a lung cancer proband. Results indicated compatibility of the data with mendelian codominant inheritance of a rare major autosomal gene that produces earlier age of onset of the cancer. Segregation at this putative locus could account for 69% and 47% of the cumulative incidence of lung cancer in individuals up to ages 50 and 60, respectively. The gene was involved in only 22% of all lung cancers in persons up to age 70, a reflection of an increasing proportion of noncarriers succumbing to the effects of long-term exposure to tobacco.
Helicobacter pylori infection is a risk factor for gastric adenocarcinoma. We examined whether this infection is also a risk factor for primary gastric non-Hodgkin's lymphoma.
This nested case-control study involved two large cohorts (230,593 participants). Serum had been collected from cohort members and stored, and all subjects were followed for cancer. Thirty-three patients with gastric non-Hodgkin's lymphoma were identified, and each was matched to four controls according to cohort, age, sex, and date of serum collection. For comparison, 31 patients with nongastric non-Hodgkin's lymphoma from one of the cohorts were evaluated, each of whom had been previously matched to 2 controls. Pathological reports and specimens were reviewed to confirm the histologic type of the tumor. Serum samples from all subjects were tested for H. pylori IgG by an enzyme-linked immunosorbent assay.
Thirty-three cases of gastric non-Hodgkin's lymphoma occurred a median of 14 years after serum collection. Patients with gastric lymphoma were significantly more likely than matched controls to have evidence of previous H. pylori infection (matched odds ratio, 6.3; 95 percent confidence interval, 2.0 to 19.9). The results were similar in both cohorts. Among the 31 patients with nongastric lymphoma, a median of six years had elapsed between serum collection and the development of disease. No association was found between nongastric non-Hodgkin's lymphoma and previous H. pylori infection (matched odds ratio, 1.2; 95 percent confidence interval, 0.5 to 3.0).
Non-Hodgkin's lymphoma affecting the stomach, but not other sites, is associated with previous H. pylori infection. A causative role for the organism is plausible, but remains unproved.
The mutation of tumor suppressor genes is thought to contribute to tumor growth by inactivating proteins that normally act to limit cell proliferation. Several tumor suppressor proteins have been identified in recent years, but only two of them, p53 and pRb, are understood in detail. In the past year, a role has become apparent for both of these proteins in transcription and phosphorylation events required for passage of a cell from G1 to S phase. The pRb protein appears to prevent the function of transcription factors and other proteins needed for S phase until its inactivation by cyclin-dependent kinases in late G1. Induction of p53 by DNA damage may act to cause cell cycle arrest or cell death by altering the transcription program of damaged cells. A detailed molecular understanding of these growth regulators is now emerging, and is the subject of this review.
To understand why oral inoculation of Helicobacter pylori resulted in continuous colonization of the stomach in germ-free athymic mice, but only temporary colonization in mice that were not germ-free.
We inoculated germ-free and "not-germ-free" euthymic mice with H. pylori and studied the resulting colonization of the stomach, comparing it against the germ-free athymic mouse model. In addition, we investigated Lactobacillus in the above-described three mouse groups.
H. pylori were detected in all germ-free athymic mice and all germ-free euthymic mice continuously. However, in all euthymic mice that were not germ-free, H. pylori was detected only temporarily after inoculation. Lactobacilli were detected only in the not-germ-free mouse group. The number of H. pylori in the germ-free euthymic mice was significantly lower than in the germ-free athymic mice during the period of this study after inoculation.
We therefore suggest that the growth of H. pylori may be suppressed by the immunological system and eradicated by Lactobacilli previously inhabiting the stomach.
Gastric cancer remains among the leading types of cancer worldwide. There is now convincing evidence linking H. pylori to adenocarcinomas of the gastric antrum, body, and fundus. These tumors are rapidly decreasing in incidence in the United States, whereas cardia tumors, tumors unassociated with H. pylori infection, are on the increase. Although criteria for causality have not been completely fulfilled for H. pylori and adenocarcinoma, there are plausible mechanisms by which chronic inflammation could induce carcinogenesis ("mitosis causes mutagenesis"). Because gastric cancer is unusual in the United States, screening and treatment of H. pylori in the general population are unwarranted. Chemoprevention in high-risk populations, however, could potentially be used to decrease risk for adenocarcinomas distal to the cardia.
The prevalence of Helicobacter pylori infection in a community is related to three factors: firstly, the rate of acquisition of infection with H. pylori--that is, incidence; secondly, the rate of loss of the infection; thirdly, the prolonged persistence of the bacterium in the gastroduodenal mucosa between infection and eradication. Variation in the prevalence of H. pylori is dominated by the great differences between communities in the incidence of H. pylori infection during childhood. The countries of the world form two groups: Group One is made up of those where the majority of children become infected with H. pylori during childhood and chronic infection continues during adult life; in Group Two only a minority of children are infected during childhood, but the prevalence of infection rises in proportion to age during adult life. Understanding the ages at which people acquire infection with H. pylori is crucial to the interpretation of H. pylori prevalence data.
The clinical and experimental work suggests the following scheme for the pathogenesis of gastric lymphoma. The first step is accumulation of lymphoid tissue (MALT) in response to infection of the stomach by H. pylori. In rare instances, this lymphoid infiltrate contains cells with a growth advantage, possibly because of a genetic change (trisomy 3?). The result is a monoclonal lymphoproliferative lesion that is responsive to H. pylori-driven T-cell help. Further genetic changes [t(1;14)?] may lead to escape from T-cell dependency and, ultimately, high-grade transformation. Low-grade B-cell gastric lymphoma serves as the paradigm for the entire group of MALT lymphomas that occur in a wide variety of extranodal sites. It is likely that the growth of this group of lymphomas is governed by a series of different antigens, many of which, like H. pylori, might be microbiologic. The challenge is to identify these agents and apply this knowledge to the treatment of other MALT lymphomas. This work also emphasizes the importance of paying attention to the histologic structure and nature of the ancillary cells in low-grade B-cell lymphomas. These cells, particularly the T cells, are not accidental passengers or necessarily representative of a "host response" to the neoplastic B cells. In low-grade MALT lymphomas, they are vital for the survival of the tumor. Similar mechanisms may be operative in nodal low-grade B-cell lymphomas and could offer new approaches to therapy.
Although the smoking epidemic is decreasing steadily in other parts of the world, it continues to spread at an accelerated rate in underdeveloped and developing countries. Turkey, among other developing countries, faces the increasing threat of tobacco-related cancers, particularly lung cancer, which is the leading cause of cancer death in both sexes. We investigated the relationship between cigarette consumption and the relative mortality rates due to lung cancer in men and women between 1965 and 1992. We found a parallelism between the increasing total and per capita cigarette consumption and the rising relative mortality from lung cancer in both sexes. Total per capita cigarette consumption rose from 1230 cigarettes per year in 1985 to 1495 in 1991, and the per capita yearly cigarette consumption over the age of 15 increased from 1850 in 1965 to 2600 in 1992. During the same period, the relative mortality from lung cancer increased from 25 to 40% in men and from 11 to 16% in women. The tar, nicotine, and carbon monoxide determinations of locally produced and imported cigarettes suggested that the high tar and carbon monoxide content of most locally produced cigarettes smoked over many years could also be a contributory factor to the increased mortality rates due to lung cancer. Only two brands of locally produced cigarettes contained lower than 12 mg of tar per cigarette as allowed in European community states, whereas half of the imported brands of cigarettes met this standard. Four of the six imported brands of cigarettes contained higher tar and carbon monoxide compared with the same brands sold in England. These findings indicate that urgent measures are necessary not only to ban all activities promoting the sale of cigarettes but also to establish standards for both national and foreign brands of cigarettes while making a greater effort to reduce active and passive smoking in the Turkish population.
Our aim was to detect Helicobacter pylori (H. pylori) from gastric biopsies of 248 patients using a novel, polymerase chain reaction (PCR)-based methodology, which simultaneously facilitates the determination of H. pylori vacA genotypes and cagA gene.
A simple methodology for sample preparation was established and PCR was performed with primer systems for the 16S rRNA, vacA, and cagA genes, thus circumventing the need to culture H. pylori and to extract DNA from biopsy samples.
Infection with H. pylori was detected in 147 (59.3%) of 248 patients. The vacA signal sequence genotype s1 was present in 104 (81.3%) of 128 H. pylori-positive patients, and 24 (18.8%) patients had the genotype s2. The vacA middle region types m1 and m2 were detected in 46 (35.9%) and 79 (61.7%) patients, respectively. The combinations s1/m2 (43%) and s1/m1 (35.9%) were found more frequently than s2/m2 (18.8%). The cagA gene was detected in 75 (72.1%) of 104 H. pylori-positive biopsies with the vacA genotype s1. All 24 biopsies with the type s2 were cagA negative. Strains of the type vacA s1 were found in 97% of H. pylori-positive patients with peptic ulcer disease and were associated with the presence of the cagA gene, whereas 96% of the strains of the type vacA s2 were detected in patients who only had nonulcer dyspepsia.
Using a novel PCR-based methodology, H. pylori 16S rRNA gene, vacA genotypes, and cagA gene can now be rapidly detected directly in gastric biopsies with high accuracy. These data demonstrate that infection with H. pylori strains of the vacA s1 genotype and the cagA gene are more likely to result in peptic ulcer disease. Determination of vacA genotypes and cagA gene may contribute to the potential clinical identification of patients at different levels of risk.
The aim of this study was to assess the seroprevalence of cytotoxin-associated gene A (cagA) and vacuolating cytotoxin gene A (vacA) of Helicobacter pylori in selected Thai populations with specific gastroduodenal diseases.
The immunoblot assay was used to detect serum antibodies against CagA and VacA obtained from the following patients: 87 cases of nonulcer dyspepsia (NUD), 61 cases of duodenal ulcer (DU), 49 cases of gastric ulcer (GU), and 10 cases of gastric cancer (GC).
Serum antibodies to CagA were detected in 75.4% of all patients (70. 1% of NUD, 78.7% of DU, 77.6% of GU, and 90% of GC). Although the prevalence of CagA seropositivity in GC patients was higher than in the other three groups, the difference was not statistically significant (p >.05).
The high seroprevalence of the CagA-positive H. pylori strain in patients with peptic ulcer, GC, and NUD indicates that this strain is common in Thai patients with gastroduodenal diseases. Furthermore, phenotypic classification of H. pylori into type 1 (CagA-positive, VacA-positive) and type 2 (CagA-negative, VacA-negative) is not a useful marker for screening patients with severe forms of gastroduodenal diseases.
The recent demonstration in animal models that H. pylori alone may be capable of inducing intestinal-type gastric cancer, and that H. felis can accelerate gastrin-induced gastric neoplasia has stimulated research on examining the mechanisms of H. pylori-associated carcinogenesis in humans. Several mechanisms are currently under investigation, including the dysregulation of the gastric epithelial cell cycle, the formation of DNA adducts, the generation of free radicals, alterations in growth factor secretion and cytokines, and the effects of decreased gastric acid secretion. This review will examine the relevant evidence acquired from human tissue studies, animal models and cell culture systems in an attempt to explore these pathways, and to evaluate the mechanisms by which H. pylori may cause gastric cancer.
Unlabelled:
An association between Helicobacter pylori (H. pylori) infection and extragastroduodenal disorders (EGDD) is still not clear. The aim of the study was to investigate the relationship between H. pylori infection and the symptoms of coronary artery disease (CAD), facial dermatological changes (FDC), gastroesophageal reflux diseases (GERD), and periodontal diseases (PD) in Polish population. The study was performed between 1996-1999 year on 7,060 adult inhabitants of municipal area of Krakow (aged 18-76, mean 46.3 year; 55.8% female, 44.2% male): 2,204 subjects with EGDD and 4,856 without symptoms of EGDD. Each patient responded to a detailed questionnaire under supervision of medical staff. The H. pylori status was assessed non-invasively using urea breath test (UBT) with capsulated low-dose 13C-UBT (38 mg). Exclusion criteria were: recent H. pylori eradication, treatment with PPI, bismuth and/or antibiotics in the last 4 weeks. Four groups of cases with EGDD symptoms were selected. Within each group exclusively only one of studied symptoms was recorded. The study included 328, 138, 688, and 1,050 patients with CAD, FDC, GERD and PD, respectively. For each studied group an age and sex-matched asymptomatic controls were selected (897, 387, 1,083, and 2,489 control patients).
Results:
Overall H. pylori infection rate was 69,9% (in 71.4% of 2,204 cases and in 69.31% of 4,856 controls). In CAD group: 68% of 328 cases were H. pylori (+ve) vs. 70% H. pylori (+ve) of 897 controls. An association was not significant: OR = 0.93 (95% CI, 0.72-1.20). In 138 of FDC cases, 59% were H. pylori (+ve) vs. 71% H. pylori (+ve) in 387 controls showing the lack of positive association; OR = 0.60 (95% CI, 0.42-0.87). In GERD, 69% of 688 cases were H. pylori (+ve) vs. 73% of 1,083 H. pylori (+ve) controls and negative association was observed; OR=0.80 (95% CI, 0.65-1.00). In 1,050 of PD cases 75% were H. pylori (+ve) vs. 68% H. pylori (+ve) of 2,489 controls; positive association was significant; OR = 1.4 (95% CI, 1.16-1.68). We conclude that in the studied Polish population, no positive association exists between H. pylori positivity and CAD, FDC or GERD possibly due very high overall H. pylori infection rate. The only positive link observed between H. pylori infection and periodontal disease may reflect direct "in situ" H. pylori pathological action of H. pylori in oral cavity. It is not excluded that periodontal diseases may facilitate the H. pylori oro-gastric transmission and colonisation of the bacteria in the digestive tract.
A number of putative virulence factors for Helicobacter pylori have been identified including cagA, vacA and iceA. The criteria for a true virulence factor includes meeting the tests of biologically plausibility with the associations being both experimentally and epidemiologically consistent. Although disease-specific associations have been hypothesized/claimed, there are now sufficient data to conclusively state that none of these putative virulence factors have disease specificity. CagA has been claimed to be associated with increased mucosal IL-8 and inflammation, increased density of H. pylori in the antrum, duodenal ulcer (DU), gastric cancer, and protection against Barrett's cancer. Only the increase in IL-8/inflammation is direct and substantiated. Different H. pylori strains with functional cag pathogenicity islands do not vary in virulance as it has been shown that mucosal IL-8 levels are proportional to the number of cagA + H. pylori independent of the disease from which the H. pylori were obtained. It is now known that the density of either cagA + and cagA-H. pylori in the antrum of patients with H. pylori gastritis is the same. In contrast, the mean density of H. pylori in the antrum in DU is greater than in the antrum of patients with H. pylori gastritis. Of interest, the density of H. pylori is higher in the corpus of patients with H. pylori gastritis than those with DU, suggesting that acid secretion plays a critical role in these phenomena. The presence of a functional cag pathogenicity island increases inflammation and it is likely that any factor that results in an increase in inflammation also increases the risk of a symptomatic outcome. Nevertheless, the presence of a functional cag pathogenicity island has no predictive value for the presence, or the future development of a clinically significant outcome. The hypothesis that iceA has disease specificity has not been confirmed and there is currently no known biological or epidemiological evidence for a role for iceA as a virulence factor in H. pylori-related disease. The claim that vacA genotyping might prove clinically useful, e.g. to predict presentation such as duodenal ulcer, has been proven wrong. Analysis of the worldwide data show that vacA genotype s1 is actually a surrogate for the cag pathogenicity island. There is now evidence to suggest that virulence is a host-dependent factor. The pattern of gastritis has withstood the test of time for its relation to different H. pylori-related diseases (e.g. antral predominant gastritis with duodenal ulcer disease). The primary factors responsible for the different patterns of gastritis in response to an H. pylori infection are environmental (e.g. diet), with the H. pylori strain playing a lesser role. Future studies should work to eliminate potential bias before claiming disease associations. Controls must exclude regional or geographic associations related to the common strain circulation and not to the outcome. The authors must also control for both the presence of the factor and for the disease association. The study should be sufficiently large and employ different diseases and ethnic groups for the results to be robust. The findings in the initial sample (data derived hypothesis) should be tested in a new group (hypothesis testing), preferably from another area, before making claims. Finally, it is important to ask whether the results are actually a surrogate for another marker (e.g. vacA s1 for cagA) masquerading for a new finding. Only the cag pathogenicity island has passed the tests of biological plausibility (increased inflammation) and experimental and epidemiological consistency.
The evidence in support of the dominant role of Helicobacter pylori in association with peptic ulcer disease (PUD) is reviewed. The epidemiology of PUD is in flux, however, and, in the future, H. pylori may become a less prevalent factor, because it now is in bleeding versus uncomplicated ulcers. Unfortunately, the accuracy of some diagnostic tests in bleeding ulcers may be lower than in uncomplicated ulcers. Concepts related to H. pylori virulence factors in ulcer disease, the pathophysiology of H. pylori ulcer disease, the interrelationships among H. pylori, NSAIDS, and ulcers, and the management of H. pylori ulcers are reviewed.
Tumors arising in the lungs are in over 90% bronchogenic carcinomas that have been attributed predominantly to tobacco smoking, asbestos or air pollution but little is known about endogenous factors that could facilitate their development and invasiveness. The lungs originate embryologically from the same endoderm cells which form the epithelia lining the digestive tract, where gastrin is the major proliferative stimulus.
Since lung cancer patients were recruited mostly among smokers, who also have been found to exhibit significantly higher infection rate of Helicobacter pylori (HP) infection than non-smokers and, as since the HP-infected subjects show enhanced plasma levels of gastrin, we decided 1) to compare the seroprevalence of HP and the expression of its cytotoxin, CagA, in lung cancer patients with those in the age- and gender-matched controls without cancer: 2) to determine the gene expression for gastrin and its receptors (CCKB-R) in lung cancer, 3) to assess the gastrin levels in plasma bronchial lavage and in tumor tissue and 4) to examine the expression of cyclooxygenase (COX)-1 and COX-2 in cancer tissue resection margin and intact bronchial mucosa.
The trial material included 50 patients with lung carcinoma and 100 age- and gender-matched controls. Anti-HP and anti-CagA IgG seroprevalence was estimated by specific antisera using ELISA tests. Gene expression of gastrin, CCKB-R, COX-1 and COX-2 was examined using RT-PCR, while gastrin was measured by specific RIA.
The seroprevalence of HP, especially that expressing CagA, is significantly higher in lung cancers than in healthy controls. Both gastrin and CCKB-R mRNA were detected in the cancer tissue and at the resection margin and similarly COX-2 mRNA was expressed in most cancers and resection margin but not in bronchial mucosa where only COX-1 was found. The lung cancer tissue and resection margin contained many folds larger amounts of immunoreactive gastrin than intact bronchial mucosa.
Helicobacter pylori is the major cause of chronic gastritis. The predominant anatomic distribution of the gastritis is antral in the majority of individuals. In a small minority, the corpus is predominantly involved. The former pattern is associated with duodenal ulceration in some patients, but the majority of those infected never develop either symptoms or disease. The latter form is associated with the development of gastric ulcer and carcinoma and may be protective against the development of Barrett's esophagus. It is the physiological changes associated with the histological changes and the, as yet poorly, defined host response, which are of paramount importance in determining the evolution of a disease or whether the infected individual remains asymptomatic and disease free. This article addresses the various relationships between H. pylori infection, histology, gastric physiology, and disease.
Helicobacter pylori, NSAID and cigarette smoking are major risk factors for gastroduodenal ulcers. However, the results of studies on the interaction between these factors on ulcerogenesis are controversial. This study was designed to examine the association between gastroduodenal ulcers and H. pylori infection, NSAID use, smoking and age.
5967 dyspeptic patients underwent 13C-urea breath test (UBT) and upper endoscopy, while age and dyspeptic symptoms were reported.
Out of 5967 patients, 31.8% were ulcerated; 9.2% had gastric, 17.2% duodenal and 5.4% both gastric and duodenal ulcers. H. pylori was found in 72.5% of gastric ulcer patients, in 83.6% of duodenal ulcer patients, in 76.9% of gastroduodenal ulcer patients and in 64.8% of dyspeptic patients. The gastric, duodenal and gastroduodenal ulcers were related to H. pylori significantly and the respective ORs were: 1.44, 2.77 and 1.81. NSAID alone was used by 6.2%-12.7% of ulcer patients, tending to raise only the risk of gastric ulcer but reducing that of duodenal and gastroduodenal ulcers. The H. pylori prevalence was significantly higher in smokers (76%) than in non-smokers (67%) and the ulcer risk was also significantly higher in smokers than in non-smokers. About 20% of ulcers were 'idiopathic', i.e. without NSAID and H. pylori and the ratio of these ulcers to all ulcers significantly increased during the 5 years of the study.
Based on multivariable logistic regression analysis we conclude that: 1) H. pylori infection, NSAID use, smoking and age play major roles in the pathogenesis of peptic ulcerations; 2) there is a negative interaction between H. pylori and NSAID on duodenal ulcers, suggesting that H. pylori reduces the development of these ulcers in NSAID users, and 3) about 20% of peptic ulcers in the Polish population are unrelated to H. pylori and NSAID use (idiopathic ulcers).
There are few data concerning the relationship between Helicobacter pylori seroconversion, and smoking habits and coffee and alcohol consumption. The aim of the present study was to investigate the relationship between smoking habits, coffee and alcohol consumption, and H. pylori seroconversion.
The data used were derived from a sample of 238 subjects (hospital employees) who were initially (on 1994) seronegative to H. pylori. These subjects were tested again 5 years later (1999). Information concerning smoking habits and coffee and alcohol consumption was collected by the use of a special questionnaire, which was completed by the same cohort of subjects in two different periods (1994 and 1999). Logistic regression was used to assess the relationship between H. pylori seroconversion and the aforementioned lifestyle factors.
Neither smoking nor coffee consumption was significantly related to H. pylori seroconversion. Adjusted odds ratio for alcohol drinkers as compared with non-/occasional drinkers was 0.59 (95% confidence interval [CI]: 0.31-1.16, P = 0.13). However, the odds ratio was significantly lower (0.26, 95%CI: 0.07-0.95, P = 0.042) in subjects who reported moderate alcohol consumption at first (1994) examination, as compared with non-/occasional drinkers. Small and heavy drinking were not associated with H. pylori seroconversion.
There is no significant relation between H. pylori seroconversion and smoking and coffee consumption. The present findings suggest that moderate alcohol consumption might be inversely associated with H. pylori seroconversion.
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Helicobacter pylori and gastric lymphoma.
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- Hansen S.
- Rodriguez L.
Gastrin in bronchogenic carcinomas: constant expression but variable processing of progastrin.
- Rehfeld J.F.
- Bardram L.
- Hilsted L.
Gastrin in bronchogenic carcinomas: constant expression but variable processing of progastrin
- Rehfeld