Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Sex-Specific Associations between Adiponectin and Leptin Signaling and Pancreatic Cancer Survival

Babic, Ana ; Wang, Qiao-Li LU orcid ; Lee, Alice A ; Yuan, Chen ; Rifai, Nader ; Luo, Juhua ; Tabung, Fred K ; Shadyab, Aladdin H ; Wactawski-Wende, Jean and Saquib, Nazmus , et al. (2023) In Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 32(10). p.1458-1469
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
publishing date
type
Contribution to journal
publication status
published
keywords
Male, Humans, Female, Leptin/genetics, Adiponectin/genetics, Adipokines, Receptors, Adiponectin/genetics, Pancreatic Neoplasms/genetics, Polymorphism, Single Nucleotide, Receptors, Leptin/genetics
in
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
volume
32
issue
10
pages
1458 - 1469
publisher
American Association for Cancer Research
external identifiers
  • scopus:85175270501
  • pmid:37555827
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-23-0505
language
English
LU publication?
no
additional info
©2023 American Association for Cancer Research.
id
1e6242e6-b6f6-4adf-ad3e-fa82ece239fd
date added to LUP
2025-05-12 17:07:37
date last changed
2025-07-08 09:52:45
@article{1e6242e6-b6f6-4adf-ad3e-fa82ece239fd,
  abstract     = {{<p>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.</p><p>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).</p><p>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).</p><p>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.</p><p>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.</p>}},
  author       = {{Babic, Ana and Wang, Qiao-Li and Lee, Alice A and Yuan, Chen and Rifai, Nader and Luo, Juhua and Tabung, Fred K and Shadyab, Aladdin H and Wactawski-Wende, Jean and Saquib, Nazmus and Kim, Jihye and Kraft, Peter and Sesso, Howard D and Buring, Julie E and Giovannucci, Edward L and Manson, JoAnn E and Stampfer, Meir J and Ng, Kimmie and Fuchs, Charles S and Wolpin, Brian M}},
  issn         = {{1538-7755}},
  keywords     = {{Male; Humans; Female; Leptin/genetics; Adiponectin/genetics; Adipokines; Receptors, Adiponectin/genetics; Pancreatic Neoplasms/genetics; Polymorphism, Single Nucleotide; Receptors, Leptin/genetics}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{10}},
  pages        = {{1458--1469}},
  publisher    = {{American Association for Cancer Research}},
  series       = {{Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}},
  title        = {{Sex-Specific Associations between Adiponectin and Leptin Signaling and Pancreatic Cancer Survival}},
  url          = {{http://dx.doi.org/10.1158/1055-9965.EPI-23-0505}},
  doi          = {{10.1158/1055-9965.EPI-23-0505}},
  volume       = {{32}},
  year         = {{2023}},
}