The assessment of probable relationship between lung cancer and Helicobacter pylori infection

Primary carcinoma of the lung is a major health problem with a generally grim prognosis. It is one of the most common causes of mortality in the world[1,2]. It is the most common cause of cancer death for both men and women and accounts for 28% of the overall cancer death rate[3].The objective of this study was to investigate the relation between lung cancer and H.pylori infection.

Material and Method

This study was conducted at the Department of Pulmonary Medicine, of the Urmia University of Medical Sciences (U.M.S.U). Urmia is a city in North West of Iran in Middle East Asia.Between April 2006 and March 2007, 66 consecutive patients with histologically verified primary lung cancer were enrolled in the study. Lung carcinoma diagnosis was confirmed by fiber optic bronchoscopy and/or trans thoracic needle aspiration

Exclusion criteria were: prior Helicobacter eradication therapy, consumption of acid suppressive drugs or antibiotics in the preceding 6 months, a history of vagotomy or operations on the upper gastrointestinal tract.

The control population included patients hospitalized for any other disease other than lung cancer. Exclusion criteria for control group were: prior Helicobacter eradication therapy, consumption of acid suppressive drugs or antibiotics in the preceding 6 months and history of vagotomy or operations on the upper gastrointestinal tract. We selected 66 controls and matched them with the patients for sex and age (within 2 years) and smoking habit.

All enrolled subjects (lung cancer patients and controls) underwent an enzyme-linked immunosorbent assay (ELISA) IgG serologic test for H. pylori diagnosis (I-Biological Laboratories Gmbh, Hamburg, Germany). This kit has a sensitivity of 100% and a specificity of 99.8%.

A positive, borderline or negative result was assigned when the concentration of IgG antibodies against H. pylori was greater than 12, between of 8-12 and less than 8, respectively. In the event of an equivocal result, a repeated test was performed on serum obtained 2 wks after the initial sampling.

Statistical analysis

The relation between lung cancer and H.pylori infection was assessed by Fisher’s exact test. All results were compared among two groups by percentage and frequency tables and charts. In addition odds ratio (OR) and 95% confidence interval were estimated for percentage of lung cancer and H.pylori infection relationship. A p value of <0.05 was considered as significant. The statistical data analysis was performed with SPSS 10.

Results

This study was carried out on 66 histologically verified lung carcinoma patients (53 men and 13 women) with the median age of 59 years (range 30 to 87 years) and 66 controls (50 men and 16 women) with the median age of 58 years (range 27 to 88 years). The demographic data of both patients and controls are shown in Table 1.

Among the lung cancer patients, 25 (37.87%) had adenocarcinoma, 21 (31.82%) had squamous cell carcinoma, 16 (24.25%) had small cell cancer , 3 (4.54%) had large cell cancer and 1 (1.52%) had broncho alveolar carcinoma.

The majority of lung cancer patients were current cigarette smokers (more than 4 daily cigarettes during one last year) (55 patients, 83.3%) and 11 patients (16.7%) were exsmokers or never smoked.

In the control group, 48 persons (72.72%) were current cigarette smoker and 18 (27.28%) persons were ex-smokers or never smoked.

There was no statistical difference in age, gender and smoking habit between the two groups (Table1).

The prevalence of H.pylori seropositivity was 3% (48/66) in patients with lung cancer but only 51% (34/66) in controls and this difference in H.pylori seropositivity between cancers and controls was statistically significant. The odds ratio for the association of H.pylori and lung cancer was 2.51 (95% CI = 1.14 – 5.54, P<0.05).

Discussion

Lung cancer is one of the most common causes of mortality in the world. During the last 50 years, its incidence is dramatically increasing, not only in men but also in women[1]. It is the most common visceral malignancy accounting for about one third of all cancer deaths in men and more than 7% of all deaths in both sexes. Lung cancer has been strongly linked to cigarette smoking. It also occurs in association with occupational and environmental exposure to carcinogenic agents[1]. There are some other factors related to the development of lung cancer such as familial predisposition, genetic alteration, and more recently H. pylori infection[4,5,6,7,8,9]. H. pylori has co-existed with humans for thousands of years. However, because scientists believed the stomach was a sterile organ, this bacterium was not discovered until the 1980s[10].

Some previous studies investigated the association between H. pylori seropositivity and lung cancer. Ece et al, found a 93% seroprevalence of antibodies against H. pylori in 40 consecutive patients with lung cancer and a 42% seroprevalence in 12 control subjects[2]. In a case-control study, Roussos et al, found a significant association between chronic bronchitis and H. pylori[11]. Philippou et al[6] failed to establish an association between H. pylori infection and lung cancer. They reported that seropositivity for H. pylori did not differ significantly between patients with lung cancer and controls (61.1% vs. 55.9% P> 0.05).

The results of our study showed that the population of patients with lung cancer has a significantly higher rate of seropositivity for antibodies against H.pylori (48 of 66) than the population of subjects without lung cancer (34 of 66). (OR=2.51, 95%CI= 1.14 – 5.54 P<0.05). However, such association was not confirmed in Najafizadeh et al study in Iran performed of 40 patients with lung cancer, which may be due to small sample size[12].

H. pylori infection in the stomach is known to be accompanied by a markedly enhanced and prolonged release of gastrin that has been suggested to account for the development of gastric cancer and has been shown to express with COX-2[8]. Furthermore, an over expression of cyclooxygenase-2 was reported in lung cancer by numerous investigators suggesting that this enzyme could be responsible for abundant release of eicosanoids, cell proliferation, angiogenesis and reduction in apoptosis, similarly as in gastric cancer[8]

H. pylori infection is accompanied by an increased plasma level of gastrin, suggesting that this hormone could contribute to the lung carcinogenesis by inducing higher mucosal cell proliferation of bronchial epithelium leading to atrophy and induction of COX-2[13,14]. Th finding that lung cancers exhibit higher expression and content of gastrin and its receptors is akin to up regulation of gastrin biosynthesis already described for gastric cancers and colorectal cancers[15]. As gastrin is known to be the most potent mucosal growth promoting factor in gastrointestinal tract (and possibly also in the bronchial mucosa), it is tempting to assume that this hormone could play a key role in the initiation and the progression of cancer disease both in the gastrointestinal tract and the lungs that embryologically originating from the same endoderm tube[8].

The reason for the higher prevalence of H.pylori infection in the lung cancer patients is not apparent but the fact that the majority of cancer patients were smokers, who are known to have higher H.pylori infection rate.Although smoking is thought to be related to H.pylori infection, some studies supporting our findings, showed no significant relation between H.pylori seroconversion and smoking[16].

In our study, 72.7% of control subjects were smokers (more than 4 daily cigarettes during last year); however, H. pylori seropositivity was significantly lower in control group than case one. So, H. pylori infection by itself may be a risk factor for lung cancer. Increased plasma level of gastrin which is accompanied by H.pylori infection may contribute to the lung cancerogenesis by inducing mucosal cell proliferation of bronchial epithelium[12].

The main limitation of this study was selection of control group. The control group population consisted of patients admitted for other diseases and were not healthy adults.

Our results suggest that H.pylori infection may have an association with lung cancer. However, further studies with larger sample size are needed to further elucidate the potential pathogenetic relationship between H.pylori infection

Acknowledgements

The authors would like to thank Farzan Institute for Research and Technology for technical assistance.

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