The risk of diffuse-type gastric cancer following diagnosis with gastric precancerous lesions: a systematic review and meta-analysis

Gastric cancers are classified as diffuse-type (DTGC) or intestinal-type (ITGC). DTGCs have distinct clinical and histopathologic features, and carry a worse overall prognosis compared to ITGCs. Atrophic gastritis (AG) and intestinal metaplasia (IM) are known precursors to ITGC. It is unknown if AG and IM increase risk for DTGC.We performed a systematic review to identify studies reporting on the association of AG/IM and DTGC. We extracted the odds ratio (OR) of the association from studies, and performed pool analysis. Subgroup analysis was performed on studies reporting histologic severity (using operative link systems) to assess if histologic severity of AG/IM was associated with higher risk.We identified six case-control and eight cohort studies for inclusion. Both AG (pooled OR = 1.9, 95% CI 1.5 to 2.4, p < 0.001) and IM (pooled OR = 2.3, 95% CI 1.9 to 2.9, p < 0.001) demonstrated an association with DTGC. High AG severity was associated with increased risk for DTGC compared to low AG severity (OR = 1.7, 95% CI 1.2 to 2.3, p = 0.002). Similarly, high IM severity was associated with increased risk compared to low IM severity (OR = 1.9, 95% CI 1.3 to 2.7, p = 0.001).Both AG and IM are associated with DTGC. Increasing histologic severity of both AG and IM increases risk for DTGC. There may exist a common pathway between ITGC and some DTGCs mediated through mucosal precursor lesions. These data may inform future strategies of cancer risk attenuation and control.