Pancreatic cancer risks associated with prediagnostic plasma levels of leptin and leptin receptor genetic polymorphisms.

Publication Type:

Journal Article

Source:

Cancer research (2016)

Abstract:

Leptin is an adipokine involved in regulating energy balance which has been identified as a potential biological link in development of obesity-associated cancers such as pancreatic cancer. In this prospective, nested case-control study of 470 cases and 1094 controls from five U.S. cohorts, we used conditional logistic regression to evaluate pancreatic cancer risk by prediagnostic plasma leptin, adjusting for race/ethnicity, diabetes, body-mass index, physical activity, plasma C-peptide, adiponectin, and 25-hydroxyvitamin D. Due to known differences in leptin levels by gender, analyses were conducted separately for men and women. We also evaluated associations between 32 tagging single nucleotide polymorphisms (SNPs) in the leptin receptor (LEPR) gene and pancreatic cancer risk. Leptin levels were higher in female versus male control participants (median, 20.8 vs. 6.7µg/mL; P0.0001). Among men, plasma leptin was positively associated with pancreatic cancer risk, and those in the top quintile had a multivariable-adjusted odds ratio (OR) of 3.02 compared to men in the bottom quintile (95% CI, 1.27-7.16; Ptrend=0.02). Among women, circulating leptin was not associated with pancreatic cancer risk (Ptrend=0.21). Results were similar across cohorts (Pheterogeneity=0.88 for two male cohorts and 0.35 for three female cohorts). In genetic analyses, rs10493380 in LEPR was associated with increased pancreatic cancer risk among women, with an OR per minor allele of 1.54 (95% CI, 1.18-2.02; multiple hypothesis-corrected P=0.03). No SNPs were significantly associated with risk in men. In conclusion, higher prediagnostic levels of plasma leptin were associated with an elevated risk of pancreatic cancer among men, but not among women.