Helicobacter pylori IgA and IgG antibodies, serum pepsinogen I and the risk of gastric cancer: Changes in the risk with extended follow‐up period

Abstract

The prediction of Helicobacter pylori antibodies immunoglobulin A (IgA) and immunoglobulin G (IgG) and serum pepsinogen I (PG I) on gastric cancer occurrence was studied in a nested case-control study, based on 225 incident cancer cases and 435 matched controls from a Finnish cohort followed from 1966-1991. The odds ratio of noncardia gastric cancer between infected and noninfected persons was 3.12 (95% confidence interval (CI) 5 1.97-4.95) for elevated IgA and 2.88 (CI: 1.63-5.07) for elevated IgG antibodies. The odds ratio between low and high PG I was 2.24 (CI: 1.43-3.49). The strength of association was significant for IgA antibodies during the total follow-up, but for IgG antibodies this was only true for follow-up periods of 15 years or more. IgA antibodies were significantly associated with all registered histological subtypes apart from intestinal type adenocarcinoma. The highest gastric cancer risk was found among individuals with simultaneously elevated IgA and IgG antibodies and low PG I with an odds ratio of 10.9 (CI: 4.31-27.7) in comparison with those who were negative for both antibodies and had normal PG I. Elevated IgA and IgG antibodies and low PG I were not associated with cancers of the gastric cardia. The findings support the hypothesis that H. pylori infection is a cause of noncardia gastric cancer. Although elevated H. pylori IgA and IgG antibodies and low PG I independently could predict the occurrence of noncardia gastric cancer, their power to do so varied with the stage and length of the follow-up period and it increased when they were applied in combination. ' 2006 Wiley-Liss, Inc.Key words: gastric cancer; H. pylori; IgA antibodies; IgG antibodies; pepsinogen I Chronic infection with Helicobacter pylori leads to chronic gastritis, which may progress to atrophy, intestinal metaplasia and finally to noncardia gastric cancer. 1,2 This hypothesis is in line with results from prospective serologic studies that have shown higher incidence of noncardia gastric cancer in subjects with H. pylori infection, verified by specific IgG antibodies, than in noninfected ones. 3 Practically, all helicobacter-infected subjects have immunoglobulin G (IgG) antibodies, whereas immunoglobulin A (IgA) antibodies are found in approximately two-thirds of infected subjects. 4 Of infected individuals, 2-3% show an elevated IgA antibody level alone. 4 In a 13-year gastric cancer follow-up of the Finnish Mobile Clinic Health Examination cohort, we demonstrated an elevated risk of the disease in persons with H. pylori antibodies of the IgA class and in those with a low serum pepsinogen I (PG I) level. Unexpectedly, however, H. pylori antibodies of the IgG class were not significantly related to the risk of gastric cancer in this cohort characterized by high prevalence of helicobacter infection also in control subjects. 5 We have now conducted a new study for a follow-up period that has been extended up to 24 years within the same study population, to clarify whether the impact of high IgA and IgG antibodies and l...

Are antibody deficiency disorders associated with a narrower range of cancers than other forms of immunodeficiency?

“…8 The increased risk of stomach cancer suggests that local gastrointestinal effects associated with PID, such as the decreased production of gastric IgA and hydrochloric acid, may facilitate Helicobacter pylori colonization and gastric inflammation and promote carcinogenesis. Although there is mixed support for such a pathogenic mechanism, [32][33][34][35] and the role for cofactors such as alterations in the p53 gene are yet to be clarified, 36 these data support the regular use of diagnostic tests and treatment of H pylori infection in adults with PID, together with endoscopic follow-up of those with premalignant gastric lesions. 37 We observed a large excess risk for thymoma on the basis of 2 cases occurring in patients with CVID.…”

Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED)

“…This indicated 21,178 endoscopies, of which 13,789 were effectively done (65%): 125 cancers were diagnosed, 80% of them at an early stage [138]. Several case-control studies comparing gastric cancer patients with healthy controls, including a range of 84 to 511 cases per study, found statistically significant odds ratios (ORs) for cancer, ranging from 2.24-12.0 for a PGI level <50 ng/mL to an OR of 2.78-10.92 for a PGI/PGII ratio <3 [139][140][141][142][143][144][145][146][147][148][149][150][151][152][153][154][155].…”

Is cardia cancer aetiologically different from distal stomach cancer?

“…The evidence supporting this lack of association, however, is based on contradictory findings (Dawsey et al, 2002;Huang et al, 1998Huang et al, , 2003. Studies from Western countries support a negative association between H. pylori infection and cardia cancer (Enroth et al, 2002;Brenner et al, 2004;Kato et al, 2004;Nomura et al, 2005;Shin et al, 2005;Kamangar et al, 2006;Knekt et al, 2006), whereas there is a trend towards positive association in studies from Eastern Asia (Kato et al, 2004;Shin et al, 2005;Yang et al, 2006;Kamangar et al, 2007;Suzuki et al, 2007).…”