In this five year prospective study, 53% of subjects were noted to have progression of gastric IM. Moreover, it was noted that 2.3% of H pylori
infected subjects developed gastric cancer over the five year follow up period. Thus the mean annual risk of gastric cancer development in our cohort was 0.46%. This value is slightly higher than that reported in the study by Uemura et al
(0.37%) which included both H pylori
infected and uninfected individuals.4
We also showed that eradication of H pylori
infection significantly retarded progression of IM. As shown in table 3, subjects randomised to receive anti-H pylori
therapy had a significantly lower risk of IM progression than those who received placebo, regardless of the final H pylori
status (OR 0.63). The risk of progression was further reduced in those with successful H pylori
eradication in the OAC group (OR 0.48). After adjusting for various confounding factors, it was determined that subjects with persistent H pylori
infection had more than a twofold increased risk of IM progression than those who were negative for H pylori
, irrespective of treatment allocation. This finding strongly supports the notion that successful eradication of the bacterium could prevent progression of precancerous gastric lesions.
As in our previous analysis,10
results from this five year analysis further confirmed that age is an important factor governing the rate of histological progression. Subjects >45 years had about a twofold increased risk of IM progression than younger subjects. The highest risk of progression was in subjects >45 years of age with persistent H pylori
infection. In keeping with this finding, You et al
concluded that the risk of progression to gastric cancer was threefold higher in subjects >45 years compared with those <45 years.14
Although it appeared that eradication of H pylori
would most benefit subjects >45 years, our analysis showed that eradication of the bacterium also significantly retarded the rate of progression in younger subjects (fig 4). Thus eradication of H pylori
should be considered in all age groups to prevent deterioration in gastric histology.
In our analysis, modifiable environmental factors, including alcohol use and drinking water from a domestic well, increased the risk of IM progression. While there are a number of studies addressing the role of tobacco and alcohol on premalignant gastric lesions,13,18
the role of the source of drinking water has received little attention. A previous study from Changle, China, showed that the source of drinking water may have a strong correlation with gastric cancer incidence.19
Gastric cancer mortality was highest among those drinking river water, which was significantly higher than those drinking shallow well water and tap water. One of the plausible explanations for this observation may be related to the mineral and trace element concentrations of drinking water. It has been shown that higher concentrations of selenium and zinc in drinking water may aid in preventing gastric carcinogenesis.20
Alternatively, the use of well water may just be a surrogate indicator of the lower socioeconomic class of these study subjects.
It is well known that not all subjects infected with H pylori
develop gastric cancer. In fact, duodenal ulcer and gastric cancer, both aetiologically linked to chronic H pylori
infection, are considered to be two ends of the clinical spectrum of H pylori
infection. While duodenal ulcer is characterised by antral predominant gastritis and acid hypersecretion, gastric cancer is characterised by corpus predominant or pangastritis with acid hyposecretion. This divergent clinical outcome may be related to the genetic makeup of the host and polymorphism in the proinflammatory cytokines.21,22
In this study, we found that duodenal ulcer patients had a lower rate of IM progression and the risk of progression was approximately 75% lower than those without duodenal ulcer. Uemura et al
also found that the risk of gastric cancer development was lower in patients with duodenal ulcers but higher in patients with gastric ulcers and non-ulcer dyspepsia.4
With the lower progression rate of gastric precancerous lesions in patients with duodenal ulcer, our finding may offer a plausible explanation for the reduced risk of gastric cancer development in these patients.
In addition to the grading of IM, there are data to suggest that subtyping of IM may further stratify the risk of gastric cancer development.23–25
Patients with type III or incomplete IM, which are characterised by the presence of columnar and globet cells secreting sulfomucins, have the highest cancer risk. However, this typing is not easily reproducible due to the focal nature of gastric IM. Instead, it has been proposed that the pattern, extent, and severity of IM may be more reliable predictors of cancer risk.26
Consistent with this, we found in the present study that the risk of IM progression was higher in those with more severe (fig 2) and more extensive IM (fig 1) at baseline. On the other hand, we failed to show any significant association between the pattern of gastritis and rate of IM progression.
Gastric IM is multifocal and is mostly indistinguishable from inflamed gastric mucosa by the naked eye or even by chromoendoscopy.27
One of the limitations of the present and other interventional studies of gastric precancerous lesions is the focal nature of these lesions which make the results subject to sampling error. To overcome this limitation, our protocol dictated the need to obtain gastric biopsies from the same landmark (that is, the mid point of the antrum and corpus in the lesser and greater curves of the stomach, during each endoscopy). Moreover, recruiting a larger sample size, incorporating a control group, and using paired tissue samples from the same subjects may have partially overcome the effects of apparent spontaneous regression of precancerous gastric lesions.
In conclusion, this five year randomised study showed that the risk of progression of gastric precancerous lesions was significantly lower in subjects with confirmed H pylori eradication or in those with duodenal ulcer. In contrast, subjects aged >45 years who drank alcohol or well water, had a higher risk of progression. Hence eradication of H pylori and lifestyle modifications may have a protective effect against gastric cancer development by retarding the progression of premalignant gastric lesions. We also identified a subgroup of infected individuals who were at high risk of histological progression that may warrant more intensive endoscopic surveillance to detect early gastric malignancy.