Cruz-Correa Marcia, Cui Hengmi, Giardiello Francis M, Powe Neil R, Hylind Linda, Robinson Angela, Hutcheon David F, Kafonek David R, Brandenburg Sheri, Wu Yiqian, He Xiaobing, Feinberg Andrew P
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Gastroenterology. 2004 Apr;126(4):964-70. doi: 10.1053/j.gastro.2003.12.051.
BACKGROUND & AIMS: Loss of genomic imprinting (LOI) of insulin-like growth factor II gene (IGF2) involves abnormal activation of the normally silent maternally inherited allele. LOI of IGF2 has been associated with personal and family history of colorectal neoplasia (CRN), supporting a role for LOI in colorectal carcinogenesis. Whether LOI of IGF2 is associated with known environmental risk factors for CRN is unknown.
We performed quantitative hot-stop PCR for imprinting analysis of IGF2 on normal peripheral blood lymphocytes (PBL) of individuals. Environmental exposures including tobacco, alcohol, NSAIDs, and nutrient consumption (calcium, folate, selenium, fiber, and fat) were correlated with LOI expression in PBL. Odds ratios (OR) and 95% CI were calculated.
The prevalence of LOI of IGF2 was examined in 172 individuals. Persons with CRN (adenomas/cancer) had 5.1-fold (95% CI: 1.92-13.6) increased risk of having LOI of IGF2 in PBL compared with those without CRN. In contrast, tobacco smoking (OR = 0.96, 95% CI: 0.36-2.55), alcohol consumption (OR = 1.22, 95% CI: 0.45-3.3), and NSAIDs use (OR = 1.21, 95% CI: 0.38-3.94) were not significantly associated with LOI of IGF2. Nutrient ingestion including calcium (P = 0.61), folate (P = 0.23), selenium (P = 0.19), fiber (P = 0.63), and fat (P = 0.14) was not statistically correlated with LOI of IGF2.
Abnormal imprinting of IGF2 gene was strongly associated with CRN but not with any of the environmental exposures examined. LOI of IGF2 does not appear to be an environmentally acquired phenomenon but rather a hereditary risk factor for CRN.
胰岛素样生长因子II基因（IGF2）的基因组印记丢失（LOI）涉及正常沉默的母系遗传等位基因的异常激活。IGF2的LOI与结直肠肿瘤（CRN）的个人和家族病史相关，支持LOI在结直肠癌发生中的作用。IGF2的LOI是否与已知的CRN环境危险因素相关尚不清楚。
我们对个体的正常外周血淋巴细胞（PBL）进行了定量热启动PCR，以分析IGF2的印记。包括烟草、酒精、非甾体抗炎药和营养物质消耗（钙、叶酸、硒、纤维和脂肪）在内的环境暴露与PBL中LOI的表达相关。计算比值比（OR）和95%置信区间（CI）。
在172名个体中检测了IGF2的LOI患病率。与无CRN的个体相比，患有CRN（腺瘤/癌症）的个体PBL中出现IGF2的LOI的风险增加了5.1倍（95%CI：1.92 - 13.6）。相比之下，吸烟（OR = 0.96，95%CI：0.36 - 2.55）、饮酒（OR = 1.22，95%CI：0.45 - 3.3）和使用非甾体抗炎药（OR = 1.21，95%CI：0.38 - 3.94）与IGF2的LOI无显著关联。包括钙（P = 0.61）、叶酸（P = 0.23）、硒（P = 0.19）、纤维（P = 0.63）和脂肪（P = 0.14）在内的营养物质摄入与IGF2的LOI无统计学相关性。
IGF2基因的异常印记与CRN密切相关，但与所检测的任何环境暴露均无关。IGF2的LOI似乎不是一种环境获得性现象，而是CRN的一种遗传危险因素。
