학술논문
Sex-Specific Associations between Adiponectin and Leptin Signaling and Pancreatic Cancer Survival.
Document Type
Academic Journal
Author
Babic A; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Wang QL; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Lee AA; Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Yuan C; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Rifai N; Department of Laboratory Medicine, Children's Hospital Boston, Boston, Massachusetts.; Luo J; Department of Epidemiology and Biostatistics, School of Public Health, Indiana University, Bloomington, Indiana.; Tabung FK; Department of Internal Medicine, Ohio State University, Columbus, Ohio.; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Shadyab AH; Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, California.; Wactawski-Wende J; Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, State University of New York, Buffalo, New York.; Saquib N; College of Medicine, Sulaiman Al Rajhi University, Al Bukairiyah, Kingdom of Saudi Arabia.; Kim J; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Kraft P; 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.; Sesso HD; 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.; Buring JE; 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.; Giovannucci EL; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.; Manson JE; 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.; Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.; Stampfer MJ; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.; Ng K; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Fuchs CS; Hematology and Oncology Product Development, Genentech & Roche, South San Francisco, California.; Wolpin BM; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Source
Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 9200608 Publication Model: Print Cited Medium: Internet ISSN: 1538-7755 (Electronic) Linking ISSN: 10559965 NLM ISO Abbreviation: Cancer Epidemiol Biomarkers Prev Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Circulating adiponectin and leptin have been associated with risk of pancreatic cancer. However, the relationship between long-term exposure to these adipokines in the prediagnostic period with patient survival has not been investigated.
Methods: Adipokine levels were measured in prospectively collected samples from 472 patients with pancreatic cancer. Because of sex-specific differences in adipokine levels, associations were evaluated separately for men and women. In a subset of 415 patients, we genotyped 23 SNPs in adiponectin receptor genes (ADIPOR1 and ADIPOR2) and 30 SNPs in the leptin receptor gene (LEPR).
Results: Adiponectin levels were inversely associated with survival in women [HR, 1.71; 95% confidence interval (CI), 1.15-2.54]; comparing top with bottom quartile but not in men (HR, 0.89; 95% CI, 0.46-1.70). The SNPs rs10753929 and rs1418445 in ADIPOR1 were associated with survival in the combined population (per minor allele HR, 0.66; 95% CI, 0.51-0.84, and HR, 1.33; 95% CI, 1.12-1.58, respectively). Among SNPs in LEPR, rs12025906, rs3790431, and rs17127601 were associated with survival in the combined population [HRs, 1.54 (95% CI, 1.25-1.90), 0.72 (95% CI, 0.59-0.88), and 0.70 (95% CI, 0.56-0.89), respectively], whereas rs11585329 was associated with survival in men only (HR, 0.39; 95% CI, 0.23-0.66; Pinteraction = 0.0002).
Conclusions: High levels of adiponectin in the prediagnostic period were associated with shorter survival among women, but not among men with pancreatic cancer. Several polymorphisms in ADIPOR1 and LEPR are associated with patient survival.
Impact: Our findings reveal the association between adipokine signaling and pancreatic cancer survival and demonstrate the importance of examining obesity-associated pathways in relation to pancreatic cancer in a sex-specific manner.
(©2023 American Association for Cancer Research.)
Methods: Adipokine levels were measured in prospectively collected samples from 472 patients with pancreatic cancer. Because of sex-specific differences in adipokine levels, associations were evaluated separately for men and women. In a subset of 415 patients, we genotyped 23 SNPs in adiponectin receptor genes (ADIPOR1 and ADIPOR2) and 30 SNPs in the leptin receptor gene (LEPR).
Results: Adiponectin levels were inversely associated with survival in women [HR, 1.71; 95% confidence interval (CI), 1.15-2.54]; comparing top with bottom quartile but not in men (HR, 0.89; 95% CI, 0.46-1.70). The SNPs rs10753929 and rs1418445 in ADIPOR1 were associated with survival in the combined population (per minor allele HR, 0.66; 95% CI, 0.51-0.84, and HR, 1.33; 95% CI, 1.12-1.58, respectively). Among SNPs in LEPR, rs12025906, rs3790431, and rs17127601 were associated with survival in the combined population [HRs, 1.54 (95% CI, 1.25-1.90), 0.72 (95% CI, 0.59-0.88), and 0.70 (95% CI, 0.56-0.89), respectively], whereas rs11585329 was associated with survival in men only (HR, 0.39; 95% CI, 0.23-0.66; Pinteraction = 0.0002).
Conclusions: High levels of adiponectin in the prediagnostic period were associated with shorter survival among women, but not among men with pancreatic cancer. Several polymorphisms in ADIPOR1 and LEPR are associated with patient survival.
Impact: Our findings reveal the association between adipokine signaling and pancreatic cancer survival and demonstrate the importance of examining obesity-associated pathways in relation to pancreatic cancer in a sex-specific manner.
(©2023 American Association for Cancer Research.)