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Roshini Claire Anthony
23 Aug 2019

Individuals with type 2 diabetes mellitus (T2D) may be at risk of developing gastric cancer even after receiving Helicobacter pylori (H. pylori) eradication therapy, demonstrated a study from Hong Kong.

“T2D was associated with an increased gastric cancer risk in H. pylori-infected patients who had received eradication therapy, especially those with suboptimal glycaemic control and who did not use metformin,” said the researchers.

A total of 46,460 patients aged 45 years (47.6 percent male) who received clarithromycin-based triple therapy* (median age at treatment 58.7 years) for H. pylori were included in this retrospective study. Of these, 14.9 percent (n=6,900) had T2D.

Patients with type 1 diabetes, history of gastric cancer or diagnosis of gastric cancer within the first year of H. pylori treatment, prior gastrectomy, or requiring repeat treatment for H. pylori were excluded.

Over a median 7.1 years, 0.33 percent of patients (n=153, median age 72.4 years) developed gastric cancer, of which 31 and 88 were in the cardia and non-cardia regions, respectively. The incidence rate of gastric cancer was 7.3 and 4.1 per 10,000 person-years among patients with and without T2D, respectively.

Patients with T2D appeared to have an elevated risk of developing gastric cancer compared with those without T2D (adjusted hazard ratio [adjHR], 1.67; p=0.021), with an absolute risk difference of 2.96 more gastric cancer cases per 10,000 person-years in those with vs without T2D. [Diabetes Care 2019;doi:10.2337/dc19-0437]

Subgroup analysis showed that compared with individuals without T2D, gastric cancer risk was elevated in patients with suboptimal glycaemic control, determined in this study as a time-weighted mean HbA1c level of 6.0 percent (adjHR, 1.68; p=0.025), but not in those with a time-weighted mean HbA1c level of <6.0 percent (adjHR, 1.99; p=0.188).

This suggests that tight glycaemic control may alleviate gastric cancer risk in patients with T2D, said the researchers.

Gastric cancer risk with T2D was also specific to cardia cancer (adjHR, 3.40; p=0.005) but not non-cardia cancer (adjHR, 1.53; p=0.161) and in patients not using metformin (adjHR, 2.59; p=0.002), with no significant effect in metformin users (adjHR, 1.28; p=0.378).

The overall risk of gastric cancer was also elevated in a sensitivity analysis which included patients diagnosed with gastric cancer within the first year of H. pylori treatment and those who repeated H. pylori treatment (adjHR, 2.12; p<0.001), with those who were retreated having a higher risk than those who received a single treatment (adjHR, 2.54; p=0.008 and adjHR, 1.98; p<0.001, respectively).

Not adjusting for aspirin, non-steroidal anti-inflammatory drugs, COX-2 inhibitors, or proton pump inhibitors (PPIs) did not significantly affect the findings. However, the association between T2D and gastric cancer was no longer significant in analysis that did not adjust for use of statins, statins plus aspirin, and all drugs. Additionally, gastric cancer risk was further elevated when comorbidities were excluded (adjHR, 1.92; p=0.002). 

“[W]e demonstrated a potential source of bias, whereby the association between T2D and gastric cancer decreased toward null if the use of certain medications was not properly adjusted for and cancer risk was inflated if comorbidities were not considered … further illustrat[ing] the importance of adjusting for concomitant medications and comorbidities,” the researchers noted.

Previous studies on the T2D-gastric cancer link have yielded contradictory findings, with some showing an elevated risk and others demonstrating no association between the two conditions. [World J Gastroenterol 2013;19:936-945; Oncotarget 2017;8:44881-44892] In addition, a Japanese study showed that patients with H. pylori with higher HbA1c levels had greater risk for gastric cancer than those with lower HbA1c levels. [Gastroenterology 2009;136:1234-1241]

“Failure to stratify patients with [diabetes] by H. pylori infection might be an important reason for this disparity,” suggested the researchers, citing other potential reasons such as variation in study design and patient ethnicity. They also acknowledged that lack of information on precancerous changes prior to H. pylori treatment, diet, and family history of gastric cancer in this study could have affected the results and recommended that patients with T2D undergo screening for gastric cancer following H. pylori treatment.

 

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Most Read Articles
06 Jul 2020
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