Gastroenterology

Gastroenterology

Volume 136, Issue 4, April 2009, Pages 1234-1241
Gastroenterology

Clinical—Alimentary Tract
Hyperglycemia Increases Risk of Gastric Cancer Posed by Helicobacter pylori Infection: A Population-Based Cohort Study

https://doi.org/10.1053/j.gastro.2008.12.045Get rights and content

Background & Aims

Although diabetes mellitus and hyperglycemia are considered to be possible risk factors for various types of malignancy, the epidemiologic evidence concerning gastric cancer is scarce. The aim of this study was to evaluate the impact of hemoglobin A1c (HbA1c) levels on gastric cancer occurrence and their interaction with Helicobacter pylori infection.

Methods

A total of 2603 Japanese subjects aged ≥40 years were stratified into 4 groups according to baseline HbA1c levels (≤4.9%, 5.0%–5.9%, 6.0%–6.9%, and ≥7.0%) and followed up prospectively for 14 years.

Results

During the follow-up, 97 subjects developed gastric cancer. The age- and sex-adjusted incidence of gastric cancer significantly increased in the 6.0%–6.9% (5.1 per 1000 person-years; P < .05) and ≥7.0% groups (5.5 per 1000 person-years; P < .05) compared with the 5.0%–5.9% group (2.5 per 1000 person-years), whereas it was slightly but not significantly high in the ≤4.9% group (3.6 per 1000 person-years). This association remained substantially unchanged even after adjusting for the confounding factors including Helicobacter pylori seropositivity, (multivariate-adjusted hazard ratio [HR], 2.13; 95% confidence interval [CI]: 1.30–3.47 for the 6.0%–6.9% group and HR, 2.69; 95% CI: 1.24–5.85 for the ≥7.0% group). Among subjects who had both high HbA1c levels (≥6.0%) and Helicobacter pylori infection, the risk of gastric cancer was dramatically elevated (interaction term, P = .004).

Conclusions

Our findings suggest that casual hyperglycemia is a risk factor for gastric cancer and is a possible cofactor increasing the risk posed by Helicobacter pylori infection.

Section snippets

Study Population

A population-based prospective study has been underway since 1961 in the town of Hisayama, a suburb of the Fukuoka metropolitan area of Kyushu Island, Japan. The age and occupational distributions for Hisayama have been almost identical to those of Japan as a whole from 1961 to the present based on data from the national census. A screening survey for the present study was performed in 1988. A detailed description of this survey has been published previously.11, 12 Briefly, of the 3390 Hisayama

Results

Table 1 compares the age- and sex-adjusted mean values or frequencies of possible risk factors for gastric cancer among the HbA1c groups. The mean age and frequency of male sex tended to increase with an increase in HbA1c levels. The frequencies of diabetes, alcohol intake, and smoking habits and mean values of body mass index and total cholesterol also increased significantly with higher HbA1c levels, but such tendencies were not observed for the frequencies of H pylori infection and history

Discussion

Our findings indicated that elevated HbA1c level was a significant risk factor for the development of gastric cancer. This association remained significant even after adjusting for other risk factors, namely, age, sex, H pylori seropositivity, history of peptic ulcer disease, body mass index, serum total cholesterol, alcohol intake, smoking habits, and dietary factors. Moreover, the coexistence of a high HbA1c level and H pylori infection dramatically increased the risk of future gastric

Acknowledgments

The authors thank the residents of the town of Hisayama for their participation in the survey and the staff of the Division of Health and Welfare of Hisayama for their cooperation with this study.

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    Conflict of interest The authors disclose no conflicts.

    Funding Supported in part by Grants-in-Aid for Scientific Research A (No. 18209024) and C (No. 20591063) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and a Health and Labour Sciences Research Grant of the Ministry of Health, Labour and Welfare of Japan (Comprehensive Research on Aging and Health: H20-Chouju-004).

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