Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Cancer Epidemiol Biomarkers Prev. 2023 Oct 2;32(10):1458-1469. doi: 10.1158/1055-9965.EPI-23-0505.
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.
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).
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).
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.
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.
循环脂联素和瘦素与胰腺癌风险相关。然而，在预诊断期内长期暴露于这些脂肪因子与患者生存之间的关系尚未得到研究。
前瞻性收集了 472 名胰腺癌患者的样本，并对其进行了脂联素水平检测。由于脂肪因子水平存在性别特异性差异，因此分别对男性和女性进行了评估。在 415 名患者的亚组中，我们对脂联素受体基因（ADIPOR1 和 ADIPOR2）中的 23 个 SNP 和瘦素受体基因（LEPR）中的 30 个 SNP 进行了基因分型。
脂联素水平与女性的生存呈负相关[风险比（HR），1.71；95%置信区间（CI），1.15-2.54]；与最高四分位组与最低四分位组比较，但与男性（HR，0.89；95% CI，0.46-1.70）无关。ADIPOR1 中的 rs10753929 和 rs1418445 与合并人群的生存相关（每个次要等位基因 HR，0.66；95% CI，0.51-0.84，和 HR，1.33；95% CI，1.12-1.58）。在 LEPR 中的 SNP 中，rs12025906、rs3790431 和 rs17127601 与合并人群的生存相关[HRs，1.54（95% CI，1.25-1.90），0.72（95% CI，0.59-0.88）和 0.70（95% CI，0.56-0.89）]，而 rs11585329 仅与男性的生存相关（HR，0.39；95% CI，0.23-0.66；P 交互=0.0002）。
在预诊断期内，高水平的脂联素与女性的生存时间更短有关，但与男性无关。ADIPOR1 和 LEPR 中的几个多态性与患者的生存相关。
我们的发现揭示了脂肪因子信号与胰腺癌生存之间的关联，并证明了以性别特异性方式检查与胰腺癌相关的肥胖相关途径的重要性。
