Circulating hormones and risk of gastric cancer by subsite in three cohort studies

BACKGROUND: Obesity has been positively associated with gastric cancer. Excess fat impacts hormones, which have been implicated in carcinogenesis. We investigated obesity-related hormones and cardia gastric cancer (CGC) and non-cardia gastric cancer (NCGC) risk. METHODS: Nested case–control studies were conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (61 CGCs, and 172 NCGCs and matched controls) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study (100 CGCs and 65 NCGCs and matched controls); serum hormones were measured. In UK-Biobank (n = 458,713), we included 137 CGCs and 92 NCGCs. Sex-specific analyses were conducted. For EPIC and ATBC, odds ratios (ORs), and for UK-Biobank hazard ratios (HRs), were estimated using conditional logistic regression and Cox regression, respectively. RESULTS: Insulin-like growth-factor-1 was positively associated with CGC and NCGC in EPIC men (OR(per 1-SD increase) 1.94, 95% CI 1.03–3.63; OR(per 1-SD increase) 1.63, 95% CI 1.05–2.53, respectively), with similar findings for CGC in UK-Biobank women (HR(per 1-SD increase) 1.76, 95% CI 1.08–2.88). Leptin in EPIC men and C-peptide in EPIC women were positively associated with NCGC (OR(T3 vs. T1) 2.72, 95% CI 1.01–7.34 and OR(per 1-SD increase) 2.17, 95% CI 1.19–3.97, respectively). Sex hormone-binding globulin was positively associated with CGC in UK-Biobank men (HR(per 1-SD increase) 1.29, 95% CI 1.02–1.64). Conversely, ghrelin was inversely associated with NCGC among EPIC and ATBC men (OR(per 1-SD increase) 0.53, 95% CI 0.34–0.84; OR(per 1-SD increase) 0.22, 95% CI 0.10–0.50, respectively). In addition, dehydroepiandrosterone was inversely associated with CGC in EPIC and ATBC men combined. CONCLUSIONS: Some obesity-related hormones influence CGC and NCGC risk. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10120-023-01414-0.