title: Circulating Leptin and Risk of Pancreatic Cancer: A Pooled Analysis From 3 Cohorts.
abstract: Adiposity is associated with pancreatic cancer; however, the underlying mechanism(s) is uncertain. Leptin is an adipokine involved in metabolic regulation, and obese individuals have higher concentrations. We conducted a pooled, nested case-control study of cohort participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and the Cancer Prevention Study II Nutrition Cohort to investigate whether prediagnostic serum leptin was associated with pancreatic cancer. A total of 731 pancreatic adenocarcinoma cases that occurred between 1986 and 2010 were included (maximum follow-up, 23 years). Incidence density-selected controls (n = 909) were matched to cases by cohort, age, sex, race, and blood draw date. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. Sex-specific quintiles were based on the distribution of the controls. Overall, serum leptin was not associated with pancreatic cancer (quintile 5 vs. quintile 1: odds ratio = 1.13, 95% confidence interval: 0.75, 1.71; Ptrend = 0.38). There was a significant interaction by follow-up time (P = 0.003), such that elevated risk was apparent only during follow-up of more than 10 years after blood draw (quintile 5 vs. quintile 1: odds ratio = 2.55, 95% confidence interval: 1.23, 5.27; Ptrend = 0.004). Our results support an association between increasing leptin concentration and pancreatic cancer; however, long follow-up is necessary to observe the relationship. Subclinical disease may explain the lack of association during early follow-up.
authors.forename: Rachael Z
authors.initials: RZ
authors.lastname: Stolzenberg-Solomon
authors.forename: Christina C
authors.initials: CC
authors.lastname: Newton
authors.forename: Debra T
authors.initials: DT
authors.lastname: Silverman
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.forename: Leticia M
authors.initials: LM
authors.lastname: Nogueira
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Weinstein
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Satu
authors.initials: S
authors.lastname: Männistö
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Jacobs
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D055088:Early Detection of Cancer; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D014408:Biomarkers, Tumor; D020738:Leptin
keywords: adiposity; insulin resistance; leptin; pancreatic cancer