Severity of Gastric Intestinal Metaplasia Can Be Used to Estimate Gastric Cancer Risk

Investigators assessed the incidence of gastric cancer due to gastric intestinal metaplasia using Operative Link on Gastric Intestinal Metaplasia staging.

Study data published in Gut demonstrate that patients with more severe gastric intestinal metaplasia (IM) are at substantially increased risk for gastric cancer.

In a cohort study of patients with and without IM, higher Operative Link on Gastric Intestinal Metaplasia (OLGIM) stage was closely correlated with risk for early gastric neoplasia (EGN). These results demonstrate the utility of a risk-stratified approach using OLGIM to identify patients who would most benefit from close surveillance for gastric cancer.

While OLGIM has been used to risk-stratify patients with IM, clinical surveillance for IM is low due to lack of large-scale clinical trials supporting its predictive utility. To better inform the risk stratification of patients with IM, investigators designed the Singapore Gastric Cancer Epidemiology and Molecular Genetics Programme (GCEP), a prospective, multicenter cohort study conducted at 4 major hospitals in Singapore.

Eligible patients were of Chinese ethnicity, aged 50 years or older, and had a history of Helicobacter pylori (HP) infection and/or premalignant gastric lesions. Participants were enrolled between 2004 and 2010. Per protocol, individuals underwent index endoscopy and completed follow-up endoscopies over a period of 5 years. Biopsies were collected for histological evaluation at each endoscopy. Severity of gastritis and IM were scored by pathologists; OLGIM stage was calculated based on the average percentage of IM representation in the antrum or corpus.

The primary study endpoint was the development of EGN, defined as a histological diagnosis of high-grade dysplasia or adenocarcinoma. The incidence rate of EGN was calculated by dividing the number of EGN cases detected during surveillance by total person-years in the study. Cox regression models were used to estimate EGN risk by IM status. Models were adjusted for established EGN risk factors, including older age, male sex, lower socioeconomic status, prior HP infection, family history of gastric cancer, and prior gastric ulcers.

The GCEP cohort consisted of 2980 patients, among whom 1321 (44.3%) were diagnosed with gastric IM either at baseline or during follow-up. Mean age in the total cohort was 59.1±6.7 years; 1541 (51.7%) were men; 47.8% had a prior history of HP infection; 22.2% were current or prior smokers; and 14.2% had a family history of gastric cancer.

A total of 21 EGN cases were identified: 13 with high-grade dysplasia and 8 with stage IA/IB gastric adenocarcinoma. Median time to development of high-grade dysplasia and stage I adenocarcinoma was 22.7 (range, 12.2-48.1) and 28.1 (range, 12.7-73.3) months, respectively. Gastric IM was strongly associated with EGN and was present in 85.7% of all EGN cases. The age-adjusted EGN incidence rates for patients with and without IM were 133.9 and 12.5 per 100,000 person-years, respectively.

In adjusted Cox regression models, gastric IM was a significant risk factor for EGN (hazard ratio [HR], 5.36; 95% CI, 1.51-19.0). Other significant risk factors for EGN included atrophic gastritis (HR, 2.69; 95% CI, 1.03-7.06), older age (HR, 1.08; 95% CI, 1.02-1.16) and positive serum pepsinogen index (HR, 4.23; 95% CI, 1.34-13.37).

In analyses stratified by OLGIM staging, greater OLGIM stage was associated with higher EGN risk. The age-adjusted EGN rates in patients with OLGIM stages I, II, and III-IV were 21.5, 108.8, and 543.8 per 100,000 person-years, respectively. Patients with stages III-IV lesions also had shorter median time to development of EGN from baseline endoscopy compared with patients with stage II lesions (22.7 vs 50.7 months; P =.01). Per adjusted regression models, the risk for EGN was significantly elevated in patients with stage II (HR, 7.34; 95% CI, 1.60-33.7) and stages III-IV (HR, 20.7; 95% CI, 5.04-85.6) lesions compared with patients with stage I lesions.

Significant smoking history further increased risk among patients with intermediate- or high-risk lesions. Specifically, patients with OLGIM stages II-IV and a smoking history of 20 or more pack-years had an HR of 3.69 (95% CI, 1.03-13.2) compared with patients in the same OLGIM stages without a smoking history.

Per these results, IM is a substantial risk factor for early gastric cancer and OLGIM staging enables risk stratification. Significant smoking history further increases EGN risk among patients with OLGIM stages II-IV.

As far as study limitations, investigators cited the cohort homogeneity: the study population included only patients of Chinese ethnicity and patients aged 50 years or older. Further studies in a larger cohort are necessary to validate these findings.

“Our GCEP cohort findings suggest that risk stratification using OLGIM offers a feasible method of prioritising high-risk patients (OLGIM III–IV) for early endoscopy surveillance in 2 years and intermediate-risk patients (OLGIM II) for endoscopy in 5 years, while the vast majority of patients with no metaplasia or focal IM (OLGIM 0–I) may not require surveillance endoscopy,” investigators wrote. They concluded, “We hope our findings would enhance awareness of risk and encourage the clinical adoption of standardised gastric mucosal sampling and OLGIM histological reporting.”


Lee JWJ, Zhu F, Srivastava S, et al. Severity of gastric intestinal metaplasia predicts the risk of gastric cancer: a prospective multicentre cohort study (GCEP). Gut. Published online May 11, 2021. doi: 10.1136/gutjnl-2021-324057