Diabetes, metformin and gastric adenocarcinoma

Diabetes may increase the risk and mortality of certain cancers, but its association with gastric adenocarcinoma is not clear. On the other hand, metformin, a first-line treatment for diabetes, may reduce cancer risks and improve cancer-related survival, but these associations have not been confirmed in gastric adenocarcinoma as well. The aim of this thesis is to evaluate if and how diabetes or its biomarkers and the use of metformin influence the risk and prognosis of gastric adenocarcinoma. Study I investigated if diabetes or prediabetes influenced the risk of gastric adenocarcinoma in a population-based Swedish cohort. Participants of the Northern Swedish Health and Disease Study were included and followed up from 1985 to 2017. Participants exposed to diabetes or prediabetes, as confirmed by self-reports or oral glucose tolerance tests, were compared with those of normoglycaemia for the incidence of gastric adenocarcinoma, identified from the Swedish Cancer Registry. Cox proportional hazard regression analyses with adjustment for sex, age, calendar year, body mass index, tobacco smoking, and education level showed no associations between prediabetes or diabetes and the risk of gastric adenocarcinoma (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.79-1.44 for prediabetes; HR 0.77, 95% CI 0.46-1.29 for diabetes). Study II was a systematic review and meta-analysis assessing associations between serum Haemoglobin A1c (HbA1c) or glucose and the risk of developing gastric cancer, based on studies identified from three databases: MEDLINE, Embase and Cochrane library. The random-effects model showed that elevated levels of serum HbA1c were associated with an increased risk of gastric cancer (pooled HR 1.36, 95% CI 1.06-1.74), but not so for elevated levels of serum glucose (pooled HR 1.11, 95% CI 0.98-1.26). Study III was a population-based cohort study evaluating whether diabetes worsened the prognosis in gastric adenocarcinoma, including all patients diagnosed