Pancreatic Cancer Risk Associated with Prediagnostic Plasma Levels of Leptin and Leptin Receptor Genetic Polymorphisms

Autor: Edward Giovannucci, JoAnn E. Manson, Laufey T. Amundadottir, Kimmie Ng, Juhua Luo, Charles S. Fuchs, Hugues Aschard, Vicente Morales-Oyarvide, Rachael Z. Stolzenberg-Solomon, Howard D. Sesso, Shuji Ogino, Julie E. Buring, Brian M. Wolpin, Zhi Rong Qian, Matthew L. Anderson, Meir J. Stampfer, John Michael Gaziano, Ying Bao, Chen Yuan, Ana Babic, Barbara B. Cochrane, Peter Kraft, Nader Rifai, Michael Pollak
Přispěvatelé: James Franck Institute, University of Chicago, Harvard School of Public Health, Program in Genetic Epidemiology and Statistical Genetics (PGESG - BOSTON), Dept of Genetics, Harvard Medical School, Harvard Medical School [Boston] (HMS)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Leptin
Male
0301 basic medicine
Cancer Research
0302 clinical medicine
Risk Factors
MESH: Risk Factors
Medicine
2. Zero hunger
Sex Characteristics
[STAT.AP]Statistics [stat]/Applications [stat.AP]
MESH: Middle Aged
MESH: Polymorphism
Single Nucleotide
MESH: Genetic Predisposition to Disease
Middle Aged
MESH: Case-Control Studies
3. Good health
Oncology
030220 oncology & carcinogenesis
Receptors
Leptin
Female
MESH: Biomarkers
Tumor
MESH: Pancreatic Neoplasms
[STAT.ME]Statistics [stat]/Methodology [stat.ME]
MESH: Sex Characteristics
medicine.medical_specialty
Adipokine
MESH: Receptors
Leptin
Adenocarcinoma
Polymorphism
Single Nucleotide
Article
03 medical and health sciences
Internal medicine
Pancreatic cancer
Biomarkers
Tumor
Humans
Genetic Predisposition to Disease
Leptin receptor
MESH: Humans
Adiponectin
business.industry
MESH: Adenocarcinoma
Case-control study
Cancer
MESH: Leptin
medicine.disease
MESH: Male
Pancreatic Neoplasms
030104 developmental biology
Endocrinology
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
Case-Control Studies
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
business
Body mass index
MESH: Female
Zdroj: Cancer Research
Cancer Research, American Association for Cancer Research, 2016, 76 (24), pp.7160-7167. ⟨10.1158/0008-5472.CAN-16-1699⟩
ISSN: 0008-5472
1538-7445
Popis: 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.
Databáze: OpenAIRE
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