北卡罗来纳州结肠癌研究中的饮食、生活方式与基因组不稳定性

Diet, lifestyle, and genomic instability in the North Carolina Colon Cancer Study.

作者信息

Satia Jessie A, Keku Temitope, Galanko Joseph A, Martin Christopher, Doctolero Ryan T, Tajima Akihiro, Sandler Robert S, Carethers John M

机构信息

Department of Global Epidemiology, Amgen, Inc., One Amgen Center Drive, 24-1-C, Thousand Oaks, CA 91320, USA.

出版信息

Cancer Epidemiol Biomarkers Prev. 2005 Feb;14(2):429-36. doi: 10.1158/1055-9965.EPI-04-0486.

DOI:10.1158/1055-9965.EPI-04-0486

PMID:15734969

Abstract

OBJECTIVE

Microsatellite instability (MSI) is one form of genomic instability that occurs in 10% to 20% of sporadic colon tumors and almost all hereditary nonpolyposis colon cancers. However, little is known about how environmental factors (e.g., diet) may influence MSI in sporadic colon cancer.

METHODS

We used data from a population-based case-control study in North Carolina (486 colon cancer cases and 1,048 controls) to examine associations of diet (total energy, macronutrients, micronutrients, and food groups) with MSI. In-person interviews elicited information on potential colon cancer risk factors, and a previously validated food frequency questionnaire adapted to include regional foods was used to assess diet over the year before diagnosis or interview date. MSI was classified as MSI-high (MSI-H) and MSI-low or microsatellite stable (MSI-L/MSS). Multivariate logistic regression models estimated energy-adjusted and non-energy-adjusted odds ratios (OR).

RESULTS

Ten percent of the cases (n = 49) had MSI-H tumors (29% African American). The strongest associations between diet and MSI were observed in case-control comparisons: there was a robust inverse association between MSI-H status and beta-carotene [OR, 0.4; 95% confidence interval (95% CI), 0.2-0.9] and positive associations with energy-adjusted refined carbohydrates (OR, 2.2; 95% CI, 0.9-5.4) and non-energy-adjusted read meat intake (OR, 2.0; 95% CI, 0.9-4.2). Compared with controls, MSI-L/MSS tumors were statistically significantly associated with energy-adjusted vitamin C, vitamin E, calcium, dietary fiber, and dark green vegetables and positively associated with total energy intake (all Ps for trend < 0.05). In case-case comparisons, no dietary factors were significantly differently related to MSI-H compared with MSI-L/MSS tumors.

CONCLUSION

Refined carbohydrate and red meat consumption may promote development of MSI-H tumors, whereas beta-carotene may be associated with lower risk.

摘要

目的

微卫星不稳定性（MSI）是基因组不稳定性的一种形式，发生于10%至20%的散发性结肠癌以及几乎所有遗传性非息肉病性结肠癌中。然而，关于环境因素（如饮食）如何影响散发性结肠癌中的MSI，人们知之甚少。

方法

我们使用了北卡罗来纳州一项基于人群的病例对照研究的数据（486例结肠癌病例和1048例对照），以研究饮食（总能量、常量营养素、微量营养素和食物类别）与MSI之间的关联。通过面对面访谈获取潜在结肠癌风险因素的信息，并使用一份经过先前验证且适用于纳入当地食物的食物频率问卷，来评估诊断前或访谈日期前一年的饮食情况。MSI被分类为高度微卫星不稳定（MSI-H）和低度微卫星不稳定或微卫星稳定（MSI-L/MSS）。多变量逻辑回归模型估计了能量调整和非能量调整的比值比（OR）。

结果

10%的病例（n = 49）患有MSI-H肿瘤（29%为非裔美国人）。在病例对照比较中观察到饮食与MSI之间最强的关联：MSI-H状态与β-胡萝卜素之间存在显著的负相关[OR，0.4；95%置信区间（95%CI），0.2 - 0.9]，与能量调整后的精制碳水化合物呈正相关（OR，2.2；95%CI，0.9 - 5.4），与非能量调整后的红肉摄入量呈正相关（OR，2.0；95%CI，0.9 - 4.2）。与对照组相比，MSI-L/MSS肿瘤与能量调整后的维生素C、维生素E、钙、膳食纤维和深绿色蔬菜在统计学上显著相关，与总能量摄入呈正相关（所有趋势P值<0.05）。在病例病例比较中，与MSI-L/MSS肿瘤相比，没有饮食因素与MSI-H有显著不同的关联。