Bostick R M, Fosdick L, Grandits G A, Lillemoe T J, Wood J R, Grambsch P, Louis T A, Potter J D
Department of Public Health Sciences-Epidemiology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157, USA.
Cancer Epidemiol Biomarkers Prev. 1997 Dec;6(12):1011-9.
Colorectal epithelial cell proliferative kinetics are altered in patients at increased risk for colon cancer: proliferation rates [labeling index (LI)] are higher and there is a shift of the proliferative zone from one confined to the lower 60% of the colonic crypt to one that includes the entire crypt (higher phi(h)). To assess factors associated with LI and phi(h), we performed a cross-sectional analysis using baseline rectal mucosal biopsies from sporadic adenoma patients participating in a chemoprevention trial. Biopsies (taken without preparatory cleansing) were taken 10 cm above the level of the anus, and proliferation was assessed by detection of endogenous S-phase-associated proliferating cell nuclear antigen by immunohistochemical methods. High-quality, scorable biopsies were obtained for 115 patients, and using analysis of covariance and multiple linear regression, the LI and phi(h) were evaluated in relation to diet and other lifestyle factors, demographics, anthropometrics, family history of colon cancer, and polyp history. Statistically significant findings included the following: (a) The LI for those in the upper versus the lowest tertile of vegetable and fruit consumption was, proportionately, 35% lower (3.4% versus 5.3%; P < 0.001); for vitamin supplement users versus nonusers, it was 36% lower (3.3 versus 5.2%; P < 0.001); for recurrent versus incident polyp patients, it was 36% higher (6.2 versus 4.0%; P < 0.001); and for those with rectal polyps only versus those with colon polyps only, it was 28% higher (6.0 versus 4.3%; P = 0.05); and (b) the phi(h) for those in the upper versus the lowest tertile of sucrose consumption was, proportionately, 48% higher (7.1% versus 3.7%; P = 0.01). These results indicate that (a) colorectal epithelial cell proliferation rates are higher in recurrent adenoma patients than in incident adenoma patients and in patients with rectal adenomas only versus those with colon adenomas only, but they are lower in patients with higher intakes of vegetables and fruit and in those who take vitamin/mineral supplements, and (b) the distribution of proliferating cells is shifted toward more inclusion of the upper 40% of the crypt in patients with higher intakes of sucrose. The pattern of positive, negative, and null associations of potential risk factors with cell proliferation is similar to that commonly found with colonic neoplasms.
结直肠癌风险增加的患者，其结直肠上皮细胞增殖动力学发生改变：增殖率[标记指数(LI)]较高，增殖区从局限于结肠隐窝下部60%的区域转移至包括整个隐窝的区域(较高的phi(h))。为评估与LI和phi(h)相关的因素，我们对参与一项化学预防试验的散发性腺瘤患者的基线直肠黏膜活检样本进行了横断面分析。活检样本(未进行准备性清洁)取自肛门水平上方10 cm处，通过免疫组织化学方法检测内源性S期相关增殖细胞核抗原评估增殖情况。为115例患者获取了高质量、可评分的活检样本，通过协方差分析和多元线性回归，评估LI和phi(h)与饮食及其他生活方式因素、人口统计学特征、人体测量学指标、结直肠癌家族史和息肉病史的关系。具有统计学意义的发现如下：(a) 蔬菜和水果摄入量处于最高三分位数组的患者与最低三分位数组的患者相比，LI相应降低35%(3.4%对5.3%；P<0.001)；服用维生素补充剂的患者与未服用者相比，LI降低36%(3.3对5.2%；P<0.001)；复发性息肉患者与初发性息肉患者相比，LI升高36%(6.2对4.0%；P<0.001)；仅患有直肠息肉的患者与仅患有结肠息肉的患者相比，LI升高28%(6.0对4.3%；P = 0.05)；(b) 蔗糖摄入量处于最高三分位数组的患者与最低三分位数组的患者相比，phi(h)相应升高48%(7.1%对3.7%；P = 0.01)。这些结果表明：(a) 复发性腺瘤患者的结直肠上皮细胞增殖率高于初发性腺瘤患者，仅患有直肠腺瘤的患者高于仅患有结肠腺瘤的患者，但蔬菜和水果摄入量较高的患者以及服用维生素/矿物质补充剂的患者增殖率较低；(b) 蔗糖摄入量较高的患者，增殖细胞的分布向更多地包含隐窝上部40%区域偏移。潜在危险因素与细胞增殖的正、负和无关联模式与结肠肿瘤中常见的模式相似。
