血清胰岛素、血糖、胰岛素抵抗指数与前列腺癌风险
Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer.
作者信息
Albanes Demetrius, Weinstein Stephanie J, Wright Margaret E, Männistö Satu, Limburg Paul J, Snyder Kirk, Virtamo Jarmo
机构信息
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Rm 3044, Bethesda, MD 20892-7242, USA.
出版信息
J Natl Cancer Inst. 2009 Sep 16;101(18):1272-9. doi: 10.1093/jnci/djp260. Epub 2009 Aug 21.
BACKGROUND
The mitogenic and growth-stimulatory effects of insulin-like growth factors appear to play a role in prostate carcinogenesis, yet any direct association of circulating insulin levels and risk of prostate cancer remains unclear.
METHODS
We investigated the relationship of the level of serum insulin, glucose, and surrogate indices of insulin resistance (ie, the molar ratio of insulin to glucose and the homeostasis model assessment of insulin resistance [HOMA-IR]) to the development of prostate cancer in a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of Finnish men. We studied 100 case subjects with incident prostate cancer and 400 noncase subjects without prostate cancer from the larger cohort. Fasting serum was collected 5-12 years before diagnosis. We determined insulin concentrations with a double-antibody immunochemiluminometric assay and glucose concentrations with a hexokinase assay. Multivariable logistic regression models estimated relative risks as odds ratios (ORs), and all statistical tests were two-sided.
RESULTS
Insulin concentrations in fasting serum that was collected on average 9.2 years before diagnosis among case subjects were 8% higher than among noncase subjects, and the molar ratio of insulin to glucose and HOMA-IR were 10% and 6% higher, respectively, but these differences were not statistically significant. Among subjects in the second through fourth insulin quartiles, compared with those in the first quartile, increased insulin levels were associated with statistically significantly increased risks of prostate cancer (OR = 1.50, 95% confidence interval [CI] = 0.75 to 3.03; OR = 1.75, 95% CI = 0.86 to 3.56; and OR = 2.55, 95% CI = 1.18 to 5.51; for the second through fourth insulin quartiles, respectively; P(trend) = .02). A similar pattern was observed with the HOMA-IR (OR = 2.10, 95% CI = 1.03 to 4.26; P(trend) = .02) for the highest vs lowest quartiles. Risk varied inconsistently with glucose concentration (P(trend) = .38). A stronger association between insulin level and prostate cancer risk was observed among leaner men and among men who were less physically active at work. Crude prostate cancer incidence was 154 prostate cancers per 100 000 person-years in the lowest quartile of fasting serum insulin vs 394 prostate cancers per 100 000 person-years in the highest quartile.
CONCLUSION
Elevated fasting levels of serum insulin (but not glucose) within the normal range appear to be associated with a higher risk of prostate cancer.
背景
胰岛素样生长因子的促有丝分裂和生长刺激作用似乎在前列腺癌发生过程中发挥作用，但循环胰岛素水平与前列腺癌风险之间的任何直接关联仍不明确。
方法
在芬兰男性的α-生育酚、β-胡萝卜素癌症预防研究队列中的一项病例队列研究中，我们调查了血清胰岛素水平、血糖以及胰岛素抵抗替代指标（即胰岛素与葡萄糖的摩尔比和胰岛素抵抗稳态模型评估[HOMA-IR]）与前列腺癌发生的关系。我们从较大的队列中选取了100例前列腺癌新发病例和400例无前列腺癌的非病例。在诊断前5 - 12年收集空腹血清。我们用双抗体免疫化学发光分析法测定胰岛素浓度，用己糖激酶法测定葡萄糖浓度。多变量逻辑回归模型将相对风险估计为比值比（OR），所有统计检验均为双侧检验。
结果
病例组诊断前平均9.2年收集的空腹血清中胰岛素浓度比非病例组高8%，胰岛素与葡萄糖的摩尔比和HOMA-IR分别高10%和6%，但这些差异无统计学意义。在胰岛素水平处于第二至第四四分位数的受试者中，与第一四分位数的受试者相比，胰岛素水平升高与前列腺癌风险显著增加相关（第二至第四四分位数的OR分别为1.50，95%置信区间[CI]=0.75至3.03；OR = 1.75，95% CI = 0.86至3.56；OR = 2.55，95% CI = 1.18至5.51；P趋势 = 0.02）。最高与最低四分位数的HOMA-IR也观察到类似模式（OR = 2.10，95% CI = 1.03至4.26；P趋势 = 0.02）。风险随葡萄糖浓度变化不一致（P趋势 = 0.38）。在较瘦的男性和工作中体力活动较少的男性中，观察到胰岛素水平与前列腺癌风险之间的关联更强。空腹血清胰岛素最低四分位数组的前列腺癌粗发病率为每10万人年154例前列腺癌，而最高四分位数组为每10万人年394例。
结论
正常范围内空腹血清胰岛素水平升高（而非血糖）似乎与前列腺癌风险较高相关。
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