JNCI：肥胖激素或可成为胰腺癌治疗的靶点

研究人员报告指出，低水平的肥胖相关激素（脂联素）与胰腺癌风险增加相关。在一项病例对照试验研究中，波士顿哈弗大学Ying Bao博士（MD、ScD）和他的同事们发现，胰腺癌患者与其确诊前一年或更早时期相比，血液样本中的激素水平显着降低。

这种联系不受吸烟、糖尿病、体重指数和其他已知或不确定的胰腺癌的风险等因素的影响。Bao和他的同事们的报告被在线发表在国家癌症研究所的杂志上。他们总结道：此项研究结果提供更多证据，证实肥胖、胰岛素抵抗和胰腺癌风险之间存在生物联系；也暗示了脂联素具有一种独立的作用。

研究人员指出，胰腺癌是美国癌症死亡的四大主要癌症之一，但它的病因学并不十分清楚。然而，越来越多的证据表明：肥胖是引发胰腺癌的重要危险因素；暗示脂肪组织分泌的脂联素也可能扮演着一个重要角色。

为确证脂联素和胰腺癌之间的关系，他们开展了5项大型的、长期的前瞻性队列研究：医疗专业人员随访研究、护士健康研究、医师健康研究、妇女健康倡议、妇女健康研究。在接近36万参与者中，他们选取468名胰腺癌患者，这些患者拥有确诊前超过1年的血液样本，并且除了非黑色素瘤外，没有患任何其他的癌症。

研究人员另随机选取1080名患者作为对照组群，该族群在年龄、吸烟和空腹状况、以及采血月份等因素均与同期组群相匹配。结果分析显示，胰腺癌患者的中位血液脂联素是6.2mcg/ml，而对照组是6.8 mcg/ml，两组间存在显着的差异性，P=0.009。

血液脂联素与癌症风险也有一个逆相关，这在5个前瞻性队列持续存在，并且是胰岛素抵抗如糖尿病的独立标记。当脂联素水平被分成5个等级时，高水平的脂联素与癌症的低风险相关。特别是与最低水平的相比更是如此：

第二等级的参与者的癌症比值为0.61，95%的置信区间为0.43到0.86。

第三等级的参与者的癌症比值为0.58，95%的置信区间为0.41到0.84。

第四等级的参与者的癌症比值为0.59，95%的置信区间为0.40到0.87。

脂联素水平最高的参与者的癌症比值为0.58，95%的置信区间为0.44到0.97。趋势很显着，P=0.04。纽约水牛城Roswell Park 癌症研究所的Jianliang Zhang博士（PhD）和Steven Hochwald博士（MD）评论说，该项研究做的很仔细，但脂联素的确切作用仍然不是很清楚。

在随后的社论中，他们一致认为，该项研究证实了在脂联素与胰腺癌风险之间存在一个联系，但是，他们又补充道，判断激素与恶性肿瘤之间的确切的相互作用仍然是非常重要的。他们认为，该项研究开创了激素有可能成为诊断标记和治疗靶点的研究课题。

Zhang和Hochwald说，“评估脂联素的早期检查有可能提高胰腺肿瘤患者的生存率。”他们说，“据此也可以推测，用治疗干预措施增加循环中脂联素有可能阻止胰腺癌的发展，和（或）提高恶性肿瘤患者的生存率。

与胰腺癌相关的拓展阅读：

• STM：中药成分雷公藤甲素可抗胰腺癌
• AJG：大量吸烟酗酒与较早患胰腺癌有关
• 触发胰腺癌需要一个以上的致癌基因
• 刘云鹏教授：晚期胰腺癌的治疗方案探索
• Int J Cancer：喝咖啡与胃癌和胰腺癌风险不相关
更多信息请点击：有关胰腺癌更多资讯

doi: 10.1093/jnci/djs474
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A Prospective Study of Plasma Adiponectin and Pancreatic Cancer Risk in Five US Cohorts

Ying Bao, Edward L. Giovannucci, Peter Kraft, Meir J. Stampfer, Shuji Ogino, Jing Ma, Julie E. Buring, Howard D. Sesso, I-Min Lee, John Michael Gaziano, Nader Rifai, Michael N. Pollak, Barbara B. Cochrane, Virginia Kaklamani, Jennifer H. Lin, JoAnn E. Manson, Charles S. Fuchs and Brian M. Wolpin

Abstract

BackgroundThe adipocyte-secreted hormone adiponectin has insulin-sensitizing and anti-inflammatory properties. Although development of pancreatic cancer is associated with states of insulin resistance and chronic inflammation, the mechanistic basis of the associations is poorly understood.MethodsTo determine whether prediagnostic plasma levels of adiponectin are associated with risk of pancreatic cancer, we conducted a nested case-control study of 468 pancreatic cancer case subjects and 1080 matched control subjects from five prospective US cohorts: Health Professionals Follow-up Study, Nurses' Health Study, Physicians' Health Study, Women's Health Initiative, and Women's Health Study. Control subjects were matched to case subjects by prospective cohort, year of birth, smoking status, fasting status, and month of blood draw. All samples for plasma adiponectin were handled identically in a single batch. Odds ratios were calculated with conditional logistic regression, and linearity of the association between adiponectin and pancreatic cancer was modeled with restricted cubic spline regression. All statistical tests were two-sided.ResultsMedian plasma adiponectin was lower in case subjects versus control subjects (6.2 vs 6.8 µg/mL, P = .009). Plasma adiponectin was inversely associated with pancreatic cancer risk, which was consistent across the five prospective cohorts (P (heterogeneity) = .49) and independent of other markers of insulin resistance (eg, diabetes, body mass index, physical activity, plasma C-peptide). Compared with the lowest quintile of adiponectin, individuals in quintiles 2 to 5 had multivariable odds ratios ([ORs] 95% confidence intervals [CIs]) of OR = 0.61 (95% CI = 0.43 to 0.86), OR = 0.58 (95% CI = 0.41 to 0.84), OR = 0.59 (95% CI = 0.40 to 0.87), and OR = 0.66 (95% CI = 0.44 to 0.97), respectively (P (trend) = .04). Restricted cubic spline regression confirmed a nonlinear association (P (nonlinearity) < .01). The association was not modified by sex, smoking, body mass index, physical activity, or C-peptide (all P (interaction) > .10).ConclusionsIn this pooled analysis, low prediagnostic levels of circulating adiponectin were associated with an elevated risk of pancreatic cancer.