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United European Gastroenterol J. 2017 February; 5(1): 32–36.
Published online 2016 June 22. doi:  10.1177/2050640616642341
PMCID: PMC5384547

Family history is an independent risk factor for the progression of gastric atrophy among patients with Helicobacter pylori infection

Abstract

Background and aim

Risk factors for progression of gastric atrophy have not been fully elucidated. The aim of this study was to evaluate the risk factors for the development of atrophic gastritis in patients with Helicobacter pylori (H. pylori ) infection.

Methods

We reviewed 206 H. pylori-infected patients retrospectively. Endoscopic gastric atrophy was classified into closed- and open-type. We conducted univariate and multivariate logistic regression analyses on the contribution of age, sex, body mass index, past history of cancer, the first-degree family history of gastric cancer, habitual smoking and alcohol drinking, and endoscopic findings of gastric ulcer or duodenal ulcer for open-type gastric atrophy.

Results

On multivariate analysis, age (odds ratio = 1.079, 95% confidence interval = 1.048–1.11, p < 0.001), family history of gastric cancer (odds ratio = 3.967, 95% confidence interval = 1.414–10.6, p = 0.006) and duodenal ulcer (odds ratio = 0.834, 95% confidence interval = 0.711–0.977, p = 0.024) were the factors independently associated with open-type gastric atrophy.

Conclusions

A first-degree family history of gastric cancer, absence of duodenal ulcer, and old age were independent risk factors for the progression of gastric atrophy among H. pylori-infected patients. Careful examination with upper gastrointestinal endoscopy is necessary in patients with such risk factors.

Keywords: Atrophic gastritis, gastric cancer, H. pylori, family history, duodenal ulcer

Introduction

Gastric cancer is one of the major causes of cancer deaths in the world.1 Progression of gastric atrophy is one of the risk factors for gastric cancer among patients with Helicobacter pylori (H. pylori) infection.2,3 Although H. pylori infection seems to be a prerequisite for atrophic gastritis, not all H. pylori-infected patients will develop atrophic gastritis. Moreover, while some patients do progress to gastric cancer, others do not. Risk factors for the progression of gastric atrophy have not been fully elucidated. The aim of this study was to evaluate the risk factors for the development of atrophic gastritis in H. pylori-infected patients.

Methods

Subjects

Patients (N = 10,251) who underwent upper gastrointestinal endoscopy between January 2009 and December 2012 in Toyoshima endoscopy clinic were retrospectively reviewed. Five patients with gastric cancer history and a previous gastric surgery were excluded from the present study. H. pylori negative patients (n = 1563) and 675 patients who had received H. pylori eradication therapy were also excluded, despite failed eradication therapy; 8418 patients with an unclear status of H. pylori infection were also excluded.

Status of H. pylori infection

The status of H. pylori infection was assessed by13 C-urea breath test, stool antigen analysis, or H. pylori-specific immunoglobulin G antibodies in the serum.4 H. pylori infection was confirmed when any one of these tests was positive.

Questionnaire

All patients had provided detailed prior information and answered a structured questionnaire to assess personal and clinical data under the supervision of a well-trained interviewer. The questionnaire included questions on age, sex, body mass index (BMI), past history of cancer, the first-degree family history of gastric cancer, habitual smoking and habitual alcohol drinking.

Endoscopic diagnosis

Upper gastrointestinal endoscopy was performed by eight experienced endoscopists (OT, KS, HY, SY, KH, TK, SM, YI in Toyoshima endoscopy clinic). Endoscopic studies have reported that the area of atrophy in patients with chronic atrophic gastritis extends from the antrum to the corpus.5,6 Kimura and Takemoto divided gastric mucosal atrophy into six stages (C-I, C-II, C-III, O-I, O-II and O-III) based on the endoscopic evaluation.7 It has been clarified that mucosal atrophy progresses sequentially from C-I to O-III. This endoscopic classification was consistent with the Sydney system of classification of gastric atrophy.8 We defined gastric mucosal atrophy of stages C-I–C-III as closed-type and that of stages O-I–O-III as open-type.9 Patients with an endoscopically identified gastric ulcer or ulcer scar were classified into the gastric ulcer group. An ulcer was defined as a localized defect in the gastric mucosa of at least 5 mm diameter and with perceptible depth, whereas smaller lesions were considered as erosions.10 Similarly, patients with an endoscopically identified duodenal ulcer or ulcer scar were classified into the duodenal ulcer group.

Statistical analysis

We evaluated the effects of age, sex, BMI, past history of cancer, the first-degree family history of gastric cancer, habitual smoking, habitual alcohol drinking, gastric ulcer and duodenal ulcer on atrophic gastritis. The clinical parameters were analyzed by a univariate logistic regression analysis. The predictors found to be associated with open-type gastric atrophy on univariate analysis (p < 0.1) were subsequently assessed by a multiple logistic regression method to identify independent factors. Age and BMI were included as continuous variables in the univariate and multivariate logistic regression method. A p value of less than 0.05 was considered statistically significant. The data were analyzed using the Stat Mate IV software (ATOMS, Tokyo, Japan).

Ethics

The study was conducted with the approval of the Ethics Committee of external organization, and informed consent was obtained from all patients. The clinical trial registration number of the University Hospital Medical Information Network was R000018541.

Results

A total of 10,251 patients underwent upper gastrointestinal endoscopy. H. pylori infection status was confirmed in 1839 patients. We investigated 206 patients, after excluding 953 patients without H. pylori infection, 675 patients after H. pylori eradication and five patients with previous gastric surgery.

Table 1 shows the characteristics of the 206 patients investigated. Among the patients, 114 had open-type gastric atrophy and 92 had closed-type gastric atrophy.

Table 1.
Characteristics of patients included in the present study

Table 2 shows the univariate and multivariate analysis for open-type gastric atrophy. On univariate analysis, old age (odds ratio = 1.083, p < 0.001), high BMI (odds ratio = 1.10, p = 0.036), family history of gastric cancer (odds ratio = 3.41, p = 0.005), duodenal ulcer (odds ratio = 0.30, p = 0.002), male sex (odds ratio = 1.765, p = 0.066),] and history of cancer (odds ratio = 3.33, p = 0.054) were associated with open-type gastric atrophy. On multivariate analysis, age (odds ratio = 1.079, 95% confidence interval (CI) = 1.048–1.11, p < 0.001), family history of gastric cancer (odds ratio = 3.967, 95% CI = 1.414–10.6, p = 0.006) and duodenal ulcer (odds ratio = 0.834, 95% CI = 0.711–0.977, p = 0.024) were factors independently associated with open-type gastric atrophy.

Table 2.
Univariate and multivariate analysis for open-type gastric atrophy

Discussion

A first-degree family history of gastric cancer, absence of duodenal ulcer, and old age were independent risk factors for the progression of gastric atrophy among H. pylori-infected patients.

Some studies showed that the first-degree relatives of patients with gastric cancer and H. pylori infection have an increased risk of atrophic gastritis.1114 However, other studies have failed to show a significant association.1519 A recent meta-analysis reported the risk of first-degree relatives developing gastric cancer in comparison with controls who had no family history of gastric cancer. For gastric atrophy and H. pylori prevalence, the pooled odds ratios with 95% CI were 2.20 (1.266–3.824) and 1.925 (1.419–2.611), respectively.20 First-degree relatives of gastric cancer patients had a significantly higher risk for developing gastric atrophy, and this paralleled with a significantly higher risk of harboring H. pylori. Most studies did not match the population by H. pylori infection status, although one study matched that in order to reduce confounding effects of H. pylori infection status.18 Therefore, the role of family history as a risk factor for atrophic gastritis was not conclusive. The present study of H. pylori-infected patients clearly showed that family history was an independent risk factor for atrophic gastritis.

Tsukui et al. also reported that the presence of duodenal ulcers reduced the risk for atrophic gastritis in dyspeptic patients.21 Some reports showed that the presence of duodenal ulcer reduced the risk of gastric cancer.9,22,23 Lu et al. reported that the presence of dupA gene was related to increased risk of duodenal ulcers, as well as that it provided increased protection against gastric atrophy and gastric cancer.24 A recent meta-analysis confirmed the importance of the dupA gene for duodenal ulcers,25 in line with our present study.

Our study showed that old age was an independent risk factor for the progression of gastric atrophy. It is believed that H. pylori infection is acquired during early childhood in the majority of the infected individuals. Therefore, aging reflects the duration of H. pylori infection. We previously reported significant improvements in gastric atrophy after H. pylori eradication therapy, especially in the earlier phase of infection.2628 These results indicate that early eradication would be desirable.

The present study has several limitations. First, we did not assess other factors such as daily salt and nitrite/N-nitrosodimethylamine intake.29 Dietary salt intake is directly associated with risk of gastric cancer,30 and high consumption of nitrites and N-nitrosodimethylamine could increase the gastric cancer risk.31 The questionnaire to assess daily salt and nitrite/N-nitrosodimethylamine intake has limited value, and it is difficult to estimate them. Second, gastric mucosal atrophy was diagnosed by endoscopic findings. Miwata et al. investigated interobserver and intraobserver agreement for endoscopic gastric mucosal atrophy using the Kimura–Takemoto Classification. The kappa value for the interobserver agreement in the experienced endoscopists was 0.474. The kappa value of intraobserver agreement in the experienced endoscopists ranged from 0.585 to 0.871. The interobserver agreement for gastric mucosal atrophy was moderate, although the intraobserver was good to excellent in the experienced endoscopists.32 In our study, the interobserver agreement might be moderate. Further studies are warranted to clarify the factors for gastric mucosal atrophy.

In conclusion, we found that a first-degree family history of gastric cancer, absence of duodenal ulcers, and old age were the independent risk factors for gastric atrophy among H. pylori-infected patients. Careful examination with upper gastrointestinal endoscopy is necessary in patients with these risk factors.

Acknowledgments

We appreciate the expertise of Shuhei Matsumoto and Yoshihiro Isomura for their endoscopic procedures.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of interest

The authors declare that there is no conflict of interest.

References

1. Nishizawa T, Suzuki H. Gastric Carcinogenesis and Underlying Molecular Mechanisms: Helicobacter pylori and Novel Targeted Therapy. Biomed Res Int 2015; 2015: 794378–794378. [PMC free article] [PubMed]
2. Suzuki H, Nishizawa T, Tsugawa H, et al. Roles of oxidative stress in stomach disorders. J Clin Biochem Nutr 2012; 50: 35–39. [PMC free article] [PubMed]
3. Naito Y, Takagi T, Okada H, et al. Expression of inducible nitric oxide synthase and nitric oxide-modified proteins in Helicobacter pylori-associated atrophic gastric mucosa. J Gastroenterol Hepatol 2008; 23(Suppl. 2): S250–S257. [PubMed]
4. Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter pylori infection – the Maastricht IV/Florence Consensus Report. Gut 2012; 61: 646–664. [PubMed]
5. Sugano K, Tack J, Kuipers EJ, et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut 2015; 64: 1353–1367. [PMC free article] [PubMed]
6. Suzuki H, Mori H. Helicobacter pylori: Helicobacter pylori gastritis – a novel distinct disease entity. Nat Rev Gastroenterol Hepatol 2015; 12: 556–557. [PubMed]
7. Kimura K, Takemoto T. An endoscopic recognition of the atrophic border and its significance in chronic gastritis. Endoscopy 1969; 1: 87–97.
8. Mihara M, Haruma K, Kamada T, et al. The role of endoscopic findings for the diagnosis of Helicobacter pylori infection: Evaluation in a country with high prevalence of atrophic gastritis. Helicobacter 1999; 4: 40–48. [PubMed]
9. Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 13 2001; 345: 784–789. [PubMed]
10. Bianchi Porro G, Parente F, Imbesi V, et al. Role of Helicobacter pylori in ulcer healing and recurrence of gastric and duodenal ulcers in longterm NSAID users. Response to omeprazole dual therapy. Gut 1996; 39: 22–26. [PMC free article] [PubMed]
11. El-Omar EM, Oien K, Murray LS, et al. Increased prevalence of precancerous changes in relatives of gastric cancer patients: Critical role of H. pylori. Gastroenterology 2000; 118: 22–30. [PubMed]
12. Chang YW, Han YS, Lee DK, et al. Role of Helicobacter pylori infection among offspring or siblings of gastric cancer patients. Int J Cancer 2002; 101: 469–474. [PubMed]
13. Jablonska M, Chlumska A. Genetic factors in the development of gastric precancerous lesions – a role of Helicobacter pylori? J Physiol Paris 2001; 95: 477–481. [PubMed]
14. Sheu BS, Yang HB, Sheu SM, et al. Higher gastric cycloxygenase-2 expression and precancerous change in Helicobacter pylori-infected relatives of gastric cancer patients. Clin Cancer Res 2003; 9: 5245–5251. [PubMed]
15. Motta CR, Cunha MP, Queiroz DM, et al. Gastric precancerous lesions and Helicobacter pylori infection in relatives of gastric cancer patients from Northeastern Brazil. Digestion 2008; 78: 3–8. [PubMed]
16. The Eurohepygast Study Group. Risk factors for atrophic chronic gastritis in a European population: Results of the Eurohepygast study. Gut 2002; 50: 779–785. [PMC free article] [PubMed]
17. Oh S, Kim N, Yoon H, et al. Risk factors of atrophic gastritis and intestinal metaplasia in first-degree relatives of gastric cancer patients compared with age-sex matched controls. J Cancer Prev 2013; 18: 149–160. [PMC free article] [PubMed]
18. Romiti A, Zullo A, Tomao S, et al. Gastric mucosa alterations in first-degree relatives of gastric cancer patients. Anticancer Res 2005; 25: 2567–2572. [PubMed]
19. Carneiro F, Taveira-Gomes A, Cabral-Correia A, et al. Characteristics of the gastric mucosa of direct relatives of patients with sporadic gastric carcinoma. Eur J Cancer Prev 1993; 2: 239–246. [PubMed]
20. Rokkas T, Sechopoulos P, Pistiolas D, et al. Helicobacter pylori infection and gastric histology in first-degree relatives of gastric cancer patients: A meta-analysis. Eur J Gastroenterol Hepatol 2010; 22: 1128–1133. [PubMed]
21. Tsukui T, Kashiwagi R, Sakane M, et al. Aging increases, and duodenal ulcer reduces the risk for intestinal metaplasia of the gastric corpus in Japanese patients with dyspepsia. J Gastroenterol Hepatol 2001; 16: 15–21. [PubMed]
22. Hansson LE, Nyren O, Hsing AW, et al. The risk of stomach cancer in patients with gastric or duodenal ulcer disease. N Engl J Med 1996; 335: 242–249. [PubMed]
23. Tanikawa C, Urabe Y, Matsuo K, et al. A genome-wide association study identifies two susceptibility loci for duodenal ulcer in the Japanese population. Nat Genet 2012; 44: 430–434. S431–S432. [PubMed]
24. Lu H, Hsu PI, Graham DY, et al. Duodenal ulcer promoting gene of Helicobacter pylori. Gastroenterology 2005; 128: 833–848. [PMC free article] [PubMed]
25. Shiota S, Matsunari O, Watada M, et al. Systematic review and meta-analysis: The relationship between the Helicobacter pylori dupA gene and clinical outcomes. Gut Pathog 2010; 2: 13–13. [PMC free article] [PubMed]
26. Nishizawa T, Suzuki H, Nakagawa I, et al. Early Helicobacter pylori eradication restores sonic hedgehog expression in the gastric mucosa of Mongolian gerbils. Digestion 2009; 79: 99–108. [PubMed]
27. Nishizawa T, Suzuki H, Nakagawa I, et al. Rebamipide-promoted restoration of gastric mucosal sonic hedgehog expression after early Helicobacter pylori eradication. Digestion 2009; 79: 259–262. [PubMed]
28. Nishizawa T, Suzuki H, Masaoka T, et al. Helicobacter pylori eradication restored sonic hedgehog expression in the stomach. Hepatogastroenterology 2007; 54: 697–700. [PubMed]
29. Saieva C, Rubio CA, Nesi G, et al. Classification of gastritis in first-degree relatives of patients with gastric cancer in a high cancer-risk area in Italy. Anticancer Res 2012; 32: 1711–1716. [PubMed]
30. D’Elia L, Rossi G, Ippolito R, et al. Habitual salt intake and risk of gastric cancer: A meta-analysis of prospective studies. Clin Nutr 2012; 31: 489–498. [PubMed]
31. Song P, Wu L, Guan W. Dietary nitrates, nitrites, and nitrosamines intake and the risk of gastric cancer: A meta-analysis. Nutrients 2015; 7: 9872–9895. [PMC free article] [PubMed]
32. Miwata T, Quach DT, Hiyama T, et al. Interobserver and intraobserver agreement for gastric mucosa atrophy. BMC Gastroenterol 2015; 15: 95–95. [PMC free article] [PubMed]

Articles from United European Gastroenterology Journal are provided here courtesy of SAGE Publications