Family history of gastric mucosal abnormality and the risk of gastric cancer: a population-based observational study.

Background: An increased prevalence of gastric premalignant abnormalities was reported among relatives of gastric cancer (GC) patients, with rather unexplored clinical significance. Methods: In Swedish computerized pathology registers, we identified, as 'index' persons, 232 681 patients who were born after 1931 and underwent endoscopic examination with stomach biopsy between 1979 and 2014. Through linkage with the Multi-Generation Register, we compiled a cohort consisting of 903 337 first-degree relatives of these biopsied patients. The relatives were grouped according to their 'family histories', defined as the first gastric mucosal diagnosis of the index person or GC family history known before that. Standardized incidence ratios (SIRs) provided comparisons with the matched general population. For internal comparisons with relatives with 'normal/minor changes' mucosal family history, hazard ratios (HRs) were derived from adjusted Cox regression modelling. Results: During follow-up, 1302 relatives developed GC. Crude incidence rates of non-cardia GC were 7.7 × 10-5 year-1 for the 'normal/minor changes' family history group (SIR = 1.0), 11.2 to 12.6 × 10-5 year-1 for precancerous changes groups (atrophic gastritis/intestinal metaplasia/dysplasia, SIR = 1.5 to 1.6), and 18.4 × 10-5 year-1 for those with a family history of GC (SIR = 2.3). HRs derived from Cox models corroborated the family history-related risk pattern, with the most conspicuous trend observed among siblings-a family history of any precancerous changes and GC was associated with, respectively, a 2.5-fold and a 3.8-fold increment in non-cardia GC hazard, compared with siblings of index persons with 'normal/minor mucosal changes'. Conclusions: The precancerous mucosal abnormalities recorded in a person's first-degree relatives may improve GC risk stratification for this person.