Journal
CANCER RESEARCH
Volume 76, Issue 24, Pages 7160-7167Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-16-1699
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Categories
Funding
- NIH [UM1 CA167552, UM1 CA186107, P01 CA87969, R01 CA49449, CA97193, CA34944, CA40360, HL26490, HL34595, KL2 TR001100, U54 CA155626, P30 DK046200, K07 CA148894, R01 CA124908, P50 CA127003]
- National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services [HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, HHSN268201600004C]
- NIH (Bethesda, MD) [CA047988, HL043851, HL080467, HL099355, UM1 CA182913]
- NCI [R35 CA197735]
- Robert T. and Judith B. Hale Fund for Pancreatic Cancer
- Perry S. Levy Fund for Gastrointestinal Cancer Research
- Pappas Family Research Fund for Pancreatic Cancer
- NIH/NCI [U01 CA210171]
- Department of Defense [CA130288]
- Lustgarten Foundation
- Pancreatic Cancer Action Network
- Noble Effort Fund
- Peter R. Leavitt Family Fund
- Wexler Family Fund
- Promises for Purple
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Leptin is an adipokine involved in regulating energy balance, which has been identified as a potential biologic link in the development of obesity-associated cancers, such as pancreatic cancer. In this prospective, nested case-control study of 470 cases and 1,094 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. Because of known differences in leptin levels by gender, analyses were conducted separately for men and women. We also evaluated associations between 32 tagging 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. 6.7 ng/mL; P < 0.0001). Among men, plasma leptin was positively associated with pancreatic cancer risk and those in the top quintile had a multivariable-adjusted OR of 3.02 [ 95% confidence interval (CI), 1.27-7.16; P-trend = 0.02] compared with men in the bottom quintile. Among women, circulating leptin was not associated with pancreatic cancer risk (P-trend = 0.21). Results were similar across cohorts (P-heterogeneity = 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). NoSNPs were significantly associated with risk in men. In conclusion, higher prediagnostic levels of plasmaleptin were associated with an elevated risk of pancreatic cancer among men, but not among women. (C)2016 AACR.
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