A Prospective Study of Plasma Adiponectin and Pancreatic Cancer Risk in Five US Cohorts
A Prospective Study of Plasma Adiponectin and Pancreatic Cancer Risk in Five US Cohorts
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DOI：
10.1093/jnci/djs474
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发表时间：
2013-01-01
影响因子：
10.3
通讯作者：
Wolpin, Brian M.
中科院分区：
文献类型：
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作者：
Bao, Ying;Giovannucci, Edward L.;Wolpin, Brian M.
背景：脂联素是脂肪细胞分泌的激素，具有胰岛素增敏和抗炎作用。虽然胰腺癌的发展与胰岛素抵抗和慢性炎症的状态有关，但这种联系的机制基础知之甚少。方法为了确定诊断前血浆脂联素水平是否与胰腺癌的风险有关，我们对来自5个前瞻性美国队列的468例胰腺癌病例和1080例匹配对照进行了巢式病例对照研究。卫生专业人员随访研究、护士健康研究、医生健康研究、妇女健康倡议和妇女健康研究。对照组受试者与病例组受试者按前瞻性队列、出生年份、吸烟状态、空腹状态和抽血月份进行匹配。所有血浆脂联素样本均在同一批次中进行相同处理。采用条件Logistic回归计算比值比，并采用限制性三次样条回归建立脂联素与胰腺癌相关性的线性模型。所有的统计检验都是双侧的。结果中位血浆脂联素在病例组比对照组低（6.2 vs 6.8 μ g/mL，P = 0.009）。血浆脂联素与胰腺癌风险呈负相关，这在5个前瞻性队列中是一致的（P-异质性= 0.49），与其他胰岛素抵抗标志物（如糖尿病、体重指数、体力活动、血浆C-肽）无关。与脂联素水平最低的五分位数相比，五分位数2至5的个体具有多变量优势比（[OR] 95%置信区间[CI]）OR = 0.61（95% CI = 0.43至0.86），OR = 0.58（95% CI = 0.41至0.84），OR = 0.59（95% CI = 0.40至0.87）和OR = 0.66（95% CI = 0.44至0.97）（P趋势= 0.04）。限制性三次样条回归证实了非线性关联（P-非线性< .01）。性别、吸烟、体重指数、体力活动或C-肽（所有P-相互作用> 0.10）均未改变这种相关性。结论在该汇总分析中，低诊断前水平的循环脂联素与胰腺癌风险升高相关。J Natl Cancer Inst 2013;105：95-103
Background The 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.Methods To 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.Results Median plasma adiponectin was lower in case subjects versus control subjects (6.2 vs 6.8 mu g/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).Conclusions In this pooled analysis, low prediagnostic levels of circulating adiponectin were associated with an elevated risk of pancreatic cancer. J Natl Cancer Inst 2013;105:95-103