Importance Marine ω-3 fatty acid has been suggested to protect against colorectal cancer. Objective To assess the effect of daily marine ω-3 fatty acid supplementation on the risk of colorectal cancer precursors, including conventional adenomas and serrated polyps. Design, Setting, and Participants This study was a prespecified ancillary study of the placebo-controlled randomized clinical trial VITAL (Vitamin D and Omega-3 Trial). An intention-to-treat analysis was used to examine the effect of daily marine ω-3 supplements among 25 871 adults in the US general population (including 5106 African American persons) free of cancer and cardiovascular disease at enrollment. Randomization was from November 2011 to March 2014, and intervention ended as planned on December 31, 2017. Interventions Marine ω-3 fatty acid, 1 g daily (which included eicosapentaenoic acid, 460 mg, and docosahexaenoic acid, 380 mg) and vitamin D3 (2000 IU daily) supplements. Main Outcomes and Measures Risk of conventional adenomas (including tubular adenoma, tubulovillous adenoma, villous adenoma, and adenoma with high-grade dysplasia) or serrated polyps (including hyperplastic polyp, traditional serrated adenoma, and sessile serrated polyp). In a subset of participants who reported receiving a diagnosis of polyp on follow-up questionnaires, endoscopic and pathologic records were obtained to confirm the diagnosis. Odds ratios (ORs) and 95% CIs were calculated using logistic regression, after adjusting for age, sex, vitamin D treatment assignment, and use of endoscopy. Secondary analyses were performed according to polyp features and participants' characteristics. Results The demographic characteristics of participants at randomization were well balanced between the treatment and placebo groups; for example, 50.6% vs 50.5% were women, and 19.7% vs 19.8% were African American persons were included in each group. The mean (SD) age was 67.1 (7.1) years in the placebo group and 67.2 (7.1) in the ω-3 treatment group. During a median follow-up of 5.3 years (range, 3.8-6.1 years), 294 cases of conventional adenomas were documented in the ω-3 group and 301 in the control group (multivariable OR, 0.98; 95% CI, 0.83-1.15) (1:1 ratio between number of cases and number of participants). In addition, 174 cases of serrated polyps were documented in the ω-3 group and 167 in the control group (OR, 1.05; 95% CI, 0.84-1.29). Null associations were found for polyp subgroups according to size, location, multiplicity, or histology. In secondary analyses, marine ω-3 treatment appeared to be associated with lower risk of conventional adenomas among individuals with low plasma levels of ω-3 index at baseline (OR, 0.76; 95% CI, 0.57-1.02; P = .03 for interaction by ω-3 index). A beneficial association of supplementation was also noted in the African American population (OR, 0.59; 95% CI, 0.35-1.00) but not in other racial/ethnic groups (P = .11 for interaction). Conclusions and Relevance Supplementation with marine ω-3 fatty acids, 1 g per day, was not associated with reduced risk of colorectal cancer precursors. A potential benefit of this supplementation for individuals with low baseline ω-3 levels or for African American persons requires further confirmation. Trial Registration ClinicalTrials.gov identifier: NCT01169259.

中文翻译：

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补充海洋 ω-3 脂肪酸对美国普通人群结直肠腺瘤和锯齿状息肉风险的影响：一项随机临床试验的预设辅助研究。

重要性 海洋 ω-3 脂肪酸已被建议用于预防结肠直肠癌。目的 评估每日补充海洋 ω-3 脂肪酸对结直肠癌前体（包括常规腺瘤和锯齿状息肉）风险的影响。设计、设置和参与者 本研究是安慰剂对照随机临床试验 VITAL（维生素 D 和 Omega-3 试验）的预先指定的辅助研究。一项意向性治疗分析用于检查美国普通人群（包括 5106 名非洲裔美国人）在登记时没有癌症和心血管疾病的 25 871 名成年人每日补充海洋 ω-3 的效果。随机化时间为 2011 年 11 月至 2014 年 3 月，干预按计划于 2017 年 12 月 31 日结束。干预海洋 ω-3 脂肪酸，每天 1 克（其中包括 460 毫克二十碳五烯酸和 380 毫克二十二碳六烯酸）和维生素 D3（每天 2000 国际单位）补充剂。主要结局和测量 常规腺瘤（包括管状腺瘤、管状绒毛状腺瘤、绒毛状腺瘤和高度不典型增生的腺瘤）或锯齿状息肉（包括增生性息肉、传统锯齿状腺瘤和无蒂锯齿状息肉）的风险。在报告在随访问卷中被诊断为息肉的一部分参与者中，获得了内窥镜和病理记录以确认诊断。在调整年龄、性别、维生素 D 治疗分配和内窥镜检查后，使用逻辑回归计算优势比 (OR) 和 95% CI。根据息肉特征和参与者的特征进行二次分析。结果 随机分组参与者的人口统计学特征在治疗组和安慰剂组之间得到了很好的平衡；例如，50.6% 和 50.5% 是女性，19.7% 和 19.8% 是非裔美国人。安慰剂组的平均 (SD) 年龄为 67.1 (7.1) 岁，ω-3 治疗组为 67.2 (7.1) 岁。在 5.3 年（范围，3.8-6.1 年）的中位随访期间，ω-3 组记录了 294 例常规腺瘤，对照组记录了 301 例（多变量 OR，0.98；95% CI，0.83-1.15 )（病例数与参与者人数的比例为 1:1）。此外，ω-3 组有 174 例锯齿状息肉，对照组有 167 例（OR，1.05；95% CI，0.84-1.29）。根据大小、位置、多重性、或组织学。在二次分析中，在基线时血浆 ω-3 指数水平较低的个体中，海洋 ω-3 治疗似乎与较低的常规腺瘤风险相关（OR，0.76；95% CI，0.57-1.02；P = .03 ω-3 指数的相互作用）。在非裔美国人人群中也发现了补充剂的有益关联（OR，0.59；95% CI，0.35-1.00），但在其他种族/族裔群体中没有发现（P = .11，交互作用）。结论和相关性 每天 1 g 补充海洋 ω-3 脂肪酸与降低结直肠癌前兆的风险无关。这种补充剂对基线 ω-3 水平低的个体或非裔美国人的潜在益处需要进一步确认。试验注册 ClinicalTrials.gov 标识符：NCT01169259。在基线时血浆 ω-3 指数水平较低的个体中，海洋 ω-3 治疗似乎与较低的常规腺瘤风险相关（OR，0.76；95% CI，0.57-1.02；P = .03，ω- 3 指数）。在非裔美国人人群中也发现了补充剂的有益关联（OR，0.59；95% CI，0.35-1.00），但在其他种族/族裔群体中没有发现（P = .11，交互作用）。结论和相关性 每天 1 g 补充海洋 ω-3 脂肪酸与降低结直肠癌前兆的风险无关。这种补充剂对基线 ω-3 水平低的个体或非裔美国人的潜在益处需要进一步确认。试验注册 ClinicalTrials.gov 标识符：NCT01169259。在基线时血浆 ω-3 指数水平较低的个体中，海洋 ω-3 治疗似乎与较低的常规腺瘤风险相关（OR，0.76；95% CI，0.57-1.02；P = .03，ω- 3 指数）。在非裔美国人人群中也发现了补充剂的有益关联（OR，0.59；95% CI，0.35-1.00），但在其他种族/族裔群体中没有发现（P = .11，交互作用）。结论和相关性 每天 1 g 补充海洋 ω-3 脂肪酸与降低结直肠癌前兆的风险无关。这种补充剂对基线 ω-3 水平低的个体或非裔美国人的潜在益处需要进一步确认。试验注册 ClinicalTrials.gov 标识符：NCT01169259。