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

Abstract

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.

Keywords: Cancer; Gastric; Hormones.