Prediagnostic plasma c-pepticle and pancreatic cancer risk in men and women
Prediagnostic plasma c-pepticle and pancreatic cancer risk in men and women
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DOI：
10.1158/1055-9965.epi-07-0182
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发表时间：
2007-10-01
影响因子：
3.8
通讯作者：
Fuchs, Charles S.
中科院分区：
文献类型：
--
作者：
Michaud, Dominique S.;Wolpin, Brian;Fuchs, Charles S.
背景：高胰岛素血症和胰岛素抵抗已被认为是长期糖尿病患者和肥胖个体中胰腺癌增加的潜在机制。最近的一项研究报告了血清胰岛素水平与胰腺癌风险之间的关联，但该人群由重度吸烟者组成，他们的发现可能无法推广到非吸烟者。方法：从四个大规模前瞻性队列中获得胰腺癌病例和匹配对照，以检查诊断前血浆 C 肽和胰岛素水平与胰腺癌之间的关联。在排除采血两年内诊断或患有基线糖尿病的病例后，在最长 20 年的随访期间诊断出 197 例胰腺癌病例。我们使用条件逻辑回归并调整胰腺癌风险因素来估计 OR 和置信区间 (0)。结果：诊断前血浆 C 肽与胰腺癌风险呈正相关（OR，1.52；95% CI，0.87-2.64，与最低四分位数相比最高，P 趋势 = 0-005）。这种关联并未因体重指数或体力活动而改变，但从不吸烟者中的关联性似乎比曾经吸烟者中的关联性稍强。空腹C肽和胰岛素与胰腺癌无关；然而，我们观察到非空腹 C 肽与胰腺癌之间存在很强的线性相关性（OR，4.24；95% CI，1.30-13.8，最高与最低四分位数，P 趋势 < 0-001）。结论：根据我们发现的与非空腹 C 肽水平呈强正相关的发现，我们提出餐后状态下的胰岛素水平可能是胰腺癌发生的相关暴露；然而，其他研究需要检验这种可能性。
Background: Hyperinsulinemia and insulin resistance have been proposed as underlying mechanisms for the increase in pancreatic cancer among long-standing diabetics and obese individuals. An association between serum insulin levels and pancreatic cancer risk was reported in a recent study, but the population was composed of heavy smokers and their findings may not be generalizable to nonsmokers.Methods: Pancreatic cancer cases and matched controls were obtained from four large-scale prospective cohorts to examine the association between prediagnostic plasma levels of C-peptide and insulin and pancreatic cancer. One hundred ninety-seven pancreatic cancer cases were diagnosed during a maximum of 20 years of follow-up, after excluding cases diagnosed within 2 years of blood collection or with baseline diabetes. We estimated OR and confidence intervals (0) using conditional logistic regression with adjustment for pancreatic cancer risk factors.Results: Prediagnostic plasma C-peptide was positively associated with pancreatic cancer risk (OR, 1.52; 95% CI, 0.87-2.64, highest compared with the lowest quartile, P-trend = 0-005). The association was not modified by body mass index or physical activity but seemed to be slightly stronger among never smokers than ever smokers. Fasting C-peptide and insulin were not related to pancreatic cancer; however, we observed a strong linear association for nonfasting C-peptide and pancreatic cancer (OR, 4.24; 95% CI, 1.30-13.8, highest versus lowest quartile, P-trend < 0-001).Conclusions: Based on our finding of a strong positive association with nonfasting C-peptide levels, we propose that insulin levels in the postprandial state may be the relevant exposure for pancreatic carcinogenesis; however, other studies will need to examine this possibility.