Suzuki Hideo, Li Yanan, Dong Xiaoqun, Hassan Manal M, Abbruzzese James L, Li Donghui
Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Unit 426, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3467-73. doi: 10.1158/1055-9965.EPI-08-0514.
Insulin-like growth factors (IGF) have been associated with risk of common human cancers, but the association between IGFs and pancreatic cancer risk is unclear. To determine whether genetic variations of IGF modify pancreatic cancer risk, we compared the frequency of six single nucleotide polymorphisms of IGF1 and IGF2 in a large-scale case control study. Single nucleotide polymorphisms were investigated using the TaqMan method in 892 patients with pancreatic ductal adenocarcinoma and 783 healthy controls who were recruited from The University of Texas M. D. Anderson Cancer Center from 2000 to 2007. Cases and controls were frequency matched by age (+/-5 years), race, and sex. Risk factor information was collected using direct interviews. We estimated odds ratios (OR) and 95% confidence intervals (95% CI) using unconditional multivariate logistic regression models. A haplotype of IGF1 gene containing the 3'-UTR Ex4 -177 G>C G allele had a significantly lower frequency in cases (0.027) than in controls (0.041; P = 0.039). A statistically significant joint effect of the IGF1 3'-UTR Ex4 -177 G>C C allele and diabetes on pancreatic cancer risk was observed. The OR (95% CI) were 1.07 (0.81-1.42), 2.12 (1.53-2.93), and 5.69 (2.63-12.3) for individuals who had the CC/CG genotype alone, diabetes alone, or both factors, respectively, compared with subjects without either of the two factors with adjustment for other risk factors. The IGF2 3'-UTR Ex4 -233C>T TT genotype was significantly associated with a reduced risk of pancreatic cancer (OR = 0.07; 95% CI = 0.01-0.57; P = 0.013). The polymorphic variants of the IGF genes may serve as a susceptibility factor for pancreatic cancer.
胰岛素样生长因子（IGF）与常见人类癌症风险相关，但IGF与胰腺癌风险之间的关联尚不清楚。为了确定IGF的基因变异是否会改变胰腺癌风险，我们在一项大规模病例对照研究中比较了IGF1和IGF2的六个单核苷酸多态性的频率。使用TaqMan方法对2000年至2007年从德克萨斯大学MD安德森癌症中心招募的892例胰腺导管腺癌患者和783名健康对照者进行单核苷酸多态性研究。病例和对照按年龄（±5岁）、种族和性别进行频率匹配。通过直接访谈收集危险因素信息。我们使用无条件多变量逻辑回归模型估计比值比（OR）和95%置信区间（95%CI）。包含3'-UTR Ex4 -177 G>C G等位基因的IGF1基因单倍型在病例中的频率（0.027）显著低于对照（0.041；P = 0.039）。观察到IGF1 3'-UTR Ex4 -177 G>C C等位基因与糖尿病对胰腺癌风险有统计学显著的联合效应。与未患这两种因素且调整了其他危险因素的受试者相比，单独具有CC/CG基因型、单独患有糖尿病或同时具有这两种因素的个体的OR（95%CI）分别为1.07（0.81-1.42）、2.12（1.53-2.93）和5.69（2.63-12.3）。IGF2 3'-UTR Ex4 -233C>T TT基因型与胰腺癌风险降低显著相关（OR = 0.07；95%CI = 0.01-0.57；P = 0.013）。IGF基因的多态性变体可能是胰腺癌的一个易感因素。
