一项针对五个美国队列中血浆脂联素与胰腺癌风险的前瞻性研究。
A prospective study of plasma adiponectin and pancreatic cancer risk in five US cohorts.
机构信息
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA 02115, USA.
出版信息
J Natl Cancer Inst. 2013 Jan 16;105(2):95-103. doi: 10.1093/jnci/djs474. Epub 2012 Dec 14.
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 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).
CONCLUSIONS
In this pooled analysis, low prediagnostic levels of circulating adiponectin were associated with an elevated risk of pancreatic cancer.
背景
脂肪细胞分泌的激素脂联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状态有关，但这些关联的机制基础仍知之甚少。
方法
为了确定预测前血浆脂联素水平是否与胰腺癌风险相关，我们对来自五个美国前瞻性队列的 468 例胰腺癌病例和 1080 例匹配对照进行了嵌套病例对照研究：健康专业人员随访研究、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。对照与病例通过前瞻性队列、出生年份、吸烟状态、禁食状态和采血月份相匹配。所有用于血浆脂联素的样本均在单一批次中以相同的方式处理。比值比通过条件逻辑回归计算，脂联素与胰腺癌之间的关联线性关系采用限制性立方样条回归建模。所有统计检验均为双侧。
结果
病例组与对照组相比，中位血浆脂联素水平较低（6.2 vs 6.8 µg/mL，P =.009）。脂联素与胰腺癌风险呈负相关，这种相关性在五个前瞻性队列中是一致的（P（异质性）=.49），并且与其他胰岛素抵抗标志物（如糖尿病、体重指数、身体活动、血浆 C 肽）无关。与脂联素最低五分位数相比，五分位 2 至 5 分位的个体多变量比值比（OR 95%置信区间[CI]）为 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），OR = 0.66（95%CI = 0.44 至 0.97）（P（趋势）=.04）。限制性立方样条回归证实了非线性关联（P（非线性）<.01）。该关联不受性别、吸烟、体重指数、身体活动或 C 肽的影响（所有 P（交互作用）>.10）。
结论
在这项汇总分析中，预测前循环脂联素水平较低与胰腺癌风险升高相关。
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