title: Pancreatic Cancer Risk Associated with Prediagnostic Plasma Levels of Leptin and Leptin Receptor Genetic Polymorphisms.
abstract: 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; Ptrend= 0.02] compared with men in the bottom quintile. 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. Cancer Res; 76(24); 7160-7. ©2016 AACR.
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Ana
authors: A
authors: Babic
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
authors: Ying
authors: Y
authors: Bao
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Zhi Rong
authors: ZR
authors: Qian
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Chen
authors: C
authors: Yuan
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.|Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors: Edward L
authors: EL
authors: Giovannucci
authors: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors: Hugues
authors: H
authors: Aschard
authors: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.|Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors: Peter
authors: P
authors: Kraft
authors: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
authors: Laufey T
authors: LT
authors: Amundadottir
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland.
authors: Rachael
authors: R
authors: Stolzenberg-Solomon
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Vicente
authors: V
authors: Morales-Oyarvide
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Kimmie
authors: K
authors: Ng
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.|Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors: Meir J
authors: MJ
authors: Stampfer
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.|Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
authors: Shuji
authors: S
authors: Ogino
authors: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.|Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, Massachusetts.
authors: Julie E
authors: JE
authors: Buring
authors: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.|Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors: Howard D
authors: HD
authors: Sesso
authors: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.|Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, Massachusetts.
authors: John Michael
authors: JM
authors: Gaziano
authors: Department of Laboratory Medicine, Children's Hospital Boston, Boston, Massachusetts.
authors: Nader
authors: N
authors: Rifai
authors: Cancer Prevention Research Unit, Department of Oncology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
authors: Michael N
authors: MN
authors: Pollak
authors: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas.
authors: Matthew L
authors: ML
authors: Anderson
authors: University of Washington School of Nursing, Seattle, Washington.
authors: Barbara B
authors: BB
authors: Cochrane
authors: Department of Community Medicine, West Virginia University, Morgantown, West Virginia.
authors: Juhua
authors: J
authors: Luo
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.|Cancer Prevention Research Unit, Department of Oncology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
authors: JoAnn E
authors: JE
authors: Manson
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
authors: Charles S
authors: CS
authors: Fuchs
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. bwolpin@partners.org.
authors: Brian M
authors: BM
authors: Wolpin
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D020738:Leptin / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054411:Receptors, Leptin / Q000097:blood / Q000235:genetics*; D012307:Risk Factors; D012727:Sex Characteristics
chemical_list: D014408:Biomarkers, Tumor; D020738:Leptin; D054411:Receptors, Leptin