Page 16 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

Chapter 1
General introduction
socioeconomic status(28, 29). The relationship H. pylori infection and gastric cancer remained controversial for some time until it was effectively ended in 1994, when an expert (IARC) working group convened and classified H. pylori infection as a carcinogen to humans, based on its association with gastric cancer and mucosa- associated lymphoid tissue lymphoma (30). Although not really subject to debate anymore, this hypothesis was confirmed in 2009 by yet another second IARC working group(31), with the added precision that H. pylori causes noncardia gastric carcinoma thus implying that infection with H. pylori is not a risk factor for gastric cancer in its totality but restricted to the distal part of the stomach. A study recently estimated that 75% of noncardia gastric are associated with H. pylori infections(31). However, it now seems that the relationship between H pylori and gastric cancer may even have been underestimated, because of inaccurate assessment of H. pylori infection status. Indeed, it has been hypothesized the necessary causal factor for gastric cancer is H. pylori infection(32). Almost all of the epidemiologic evidence on the relationship between gastric cancer and H. pylori comes from a serologic assessment of H. pylori IgG. It is now widely accepted that retrospective serologic evaluation of gastric cancer with H. pylori infection cases has poor sensitivity so that case-control studies systematically underestimate the strength of the association. Atrophic gastritis causes this problem, a precancerous lesion, which leads to a reduction in infection burden to H. pylori and a subsequent decrease in IgG antibody titers to H. pylori, which may become serologically undetectable. For this reason, most of the evidence for the carcinogenicity of H. pylori is from prospective studies. The most comprehensive comparative risk estimates for H. pylori association with gastric cancer come from 12 prospective studies pooled analysis, which included cases of noncardia gastric cancer (762 ) and controls (2250). The combined (OR) of H. pylori infection was 2.97(2.34–3.77)(33). The same author included 274 cardia gastric cancer cases with the same control (827, ) with (OR) 0.99 (0.40–1.77) for H. pylori infection. When restricted cases in a pooled analysis of over ten years blood are drawn H. pylori diagnosis, an increased Odd ratio of 5.93 (3.41–10.3) for non- gastric cancer of noncardia origin but reduced odds ratio of 0.46(0.23–0.90) for cardia cancer. This subgroup analysis underscores both the difference between cardia and noncardia cancer and the need to account for the effect of gastric carcinogenesis on H. pylori measurement, even in prospective studies(31). It is important to note, however, that although H. pylori infection may explain most if not all gastric cancers, most people infected with the bacterium do not develop such cancer. Hence understanding what makes an H. pylori-dependent infection potentially hazardous is of utmost importance
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