Genetic variation in adipokine genes and associations with adiponectin and leptin concentrations in plasma and breast tissue

Abstract

Background: Circulating adipokines may be associated with breast cancer risk. Genetic variants governing adipokines and adipokine receptors may also predict risk, but their effect on breast adipokine concentrations is unknown. Methods: We conducted a cross-sectional analysis of functional SNPs in 5 adipokine genes [adiponectin, leptin (LEP), and their receptors] among 85 cancer-free women who were undergoing reduction mammoplasty. Results: In multivariable-adjusted regression models, compared with the common GG genotype, the AA genotype of the LEP A19G SNP was associated with 27% lower plasma adiponectin [ratio, 0.73; 95% confidence interval (CI), 0.54-0.98] and leptin (ratio, 0.73; 95% CI, 0.55-0.96). Women with the AG genotype of LEP A19G had 39% lower breast leptin (ratio, 0.61; 95% CI, 0.39-0.97) compared with those with the GG genotype. No associations were observed for SNPs in the remaining genes. Conclusions: Genetic variation in LEP may alter endogenous adipokine concentrations in circulation and in breast tissues. Impact: These preliminary findings may support the hypothesis that genetic variation in adipokine genes modifies circulating adipokine concentrations and possibly leptin concentrations in local breast tissues, which may be associated with breast cancer risk. © 2014 American Association for Cancer Research.