MacLennan R, Macrae F, Bain C, Battistutta D, Chapuis P, Gratten H, Lambert J, Newland R C, Ngu M, Russell A, Ward M, Wahlqvist M L
Queensland Institute of Medical Research, Brisbane, Australia.
J Natl Cancer Inst. 1995 Dec 6;87(23):1760-6. doi: 10.1093/jnci/87.23.1760.
Epidemiologic evidence of associations between the high intake of fat and low intake of dietary fiber, beta carotene, and other dietary constituents and the risk of colorectal neoplasia has been inconsistent and has not provided a sufficient basis for recommendations concerning the dietary prevention of large-bowel cancer in humans.
We conducted a clinical trial to assess the effects on the incidence of adenomas of reducing dietary fat to 25% of total calories and supplementing the diet with 25 g of wheat bran daily and a capsule of beta carotene (20 mg daily).
We performed a randomized, partially double-blinded, placebo-controlled factorial trial in which half the patients were assigned to each intervention, resulting in seven intervention groups and one control group. Eligibility criteria included histologic confirmation of at least one colorectal adenoma and confidence expressed by the colonoscopist that all polyps had been removed. Dietary changes were individually initiated and monitored by dietitians and research nurses. At surveillance colonoscopy, the size and location of all polyps were recorded, and their histology was later centrally reviewed. Among 424 patients who were randomly assigned in the trial, 13 were found to be ineligible upon histologic review. Among the remaining 411, complete outcome data were collected from 390 at 24 months and from 306 at 48 months. All P values are from two-sided tests of statistical significance.
There was no statistically significant prevention of total new adenomas with any of the interventions. We found a statistically non-significant reduced risk of large adenomas (> or = 10 mm) with the low-fat intervention: At 24 months, the odds ratio (OR) adjusted for potential confounders = 0.4 and 95% confidence interval (CI) = 0.1-1.1; at 48 months, OR = 0.3 and 95% CI = 0.1-1.0. Less and statistically nonsignificant reductions in the risk of large adenomas were found with wheat bran: At 24 months, OR = 0.8 and 95% CI = 0.3-2.2; at 48 months, OR = 0.8 and 95% CI = 0.3-2.5. Patients on the combined intervention of low fat and added wheat bran had zero large adenomas at both 24 and 48 months, a statistically significant finding (P = .03).
Because only small numbers of patients were studied, our finding that the combination of fat reduction and a supplement of wheat bran reduced the incidence of large adenomas in this randomized, controlled trial must be treated with caution. The results do suggest, however, that these interventions may reduce the transition from smaller to larger adenomas, a step that may critically define those adenomas most likely to progress to malignancy.
关于高脂肪摄入、膳食纤维、β-胡萝卜素及其他膳食成分低摄入与结直肠肿瘤风险之间关联的流行病学证据并不一致，也未为人类结直肠癌饮食预防建议提供充分依据。
我们开展了一项临床试验，以评估将膳食脂肪降至总热量的25%，并每日补充25克麦麸和一粒β-胡萝卜素胶囊（每日20毫克）对腺瘤发生率的影响。
我们进行了一项随机、部分双盲、安慰剂对照的析因试验，其中一半患者被分配到每种干预措施，从而形成七个干预组和一个对照组。入选标准包括至少一个结直肠腺瘤的组织学确诊，以及结肠镜检查医生确信所有息肉均已切除。饮食变化由营养师和研究护士单独启动并监测。在监测结肠镜检查时，记录所有息肉的大小和位置，随后对其组织学进行集中审查。在试验中随机分配的424例患者中，经组织学审查发现13例不符合入选标准。在其余411例中，在24个月时从390例收集了完整的结局数据，在48个月时从306例收集了完整的结局数据。所有P值均来自双侧统计学显著性检验。
任何一种干预措施对新发腺瘤总数均无统计学显著的预防作用。我们发现低脂干预使大腺瘤（≥10毫米）风险有统计学上不显著的降低：在24个月时，经潜在混杂因素调整后的比值比（OR）=0.4，95%置信区间（CI）=0.1 - 1.1；在48个月时，OR = 0.3，95% CI = 0.1 - 1.0。麦麸使大腺瘤风险降低幅度较小且无统计学显著性：在24个月时，OR = 0.8，95% CI = 0.3 - 2.2；在48个月时，OR = 0.8，95% CI = 0.3 - 2.5。低脂加麦麸联合干预的患者在24个月和48个月时大腺瘤均为零，这是一个有统计学显著性的发现（P = 0.03）。
由于仅研究了少量患者，我们在这项随机对照试验中发现的脂肪减少与麦麸补充联合使用可降低大腺瘤发生率这一结果必须谨慎对待。然而，结果确实提示，这些干预措施可能会减少从较小腺瘤向较大腺瘤的转变，这一步骤可能对那些最有可能进展为恶性肿瘤的腺瘤起关键定义作用。
