Background & Aims

Dietary patterns affect systemic and local intestinal inflammation, which have been linked to colorectal carcinogenesis. Chronic inflammation can interfere with the adaptive immune response. We investigated whether the association of a diet that promotes intestinal inflammation with risk of colorectal carcinoma was stronger for tumors with lower lymphocytic reactions than tumors with higher lymphocytic reactions.

Methods

We collected data from the molecular pathological epidemiology databases of 2 prospective cohort studies: the Nurses’ Health Study (since 1976) and the Health Professionals Follow-Up Study (since 1986). We used duplication-method time-varying Cox proportional cause-specific hazards regression to assess the association of empirical dietary inflammatory pattern (EDIP) score (derived from food frequency questionnaire data) with colorectal carcinoma subtype. Foods that contribute to high EDIP scores include red and processed meats, refined grains, carbonated beverages, and some vegetables; foods that contribute to low EDIP scores include beer, wine, coffee, tea, yellow and leafy vegetables, and fruit juice. Colorectal tissue samples were analyzed histologically for patterns of lymphocytic reactions (Crohn’s-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, and tumor-infiltrating lymphocytes).

Results

During follow-up of 124,433 participants, we documented 1311 incident colon and rectal cancer cases with available tissue data. The association between the EDIP and colorectal cancer risk was significant (P_trend = .02), and varied with degree of peritumoral lymphocytic reaction (P_{heterogeneity} < .001). Higher EDIP scores were associated with increased risk of colorectal cancer with an absent or low peritumoral lymphocytic reaction (highest vs lowest EDIP score quintile hazard ratio, 2.60; 95% confidence interval, 1.60−4.23; P_trend < .001), but not risk of tumors with intermediate or high peritumoral lymphocytic reaction (P_trend > .80).

Conclusions

In 2 prospective cohort studies, we associated inflammatory diets with a higher risk of colorectal cancer subtype that contains little or no peritumoral lymphocytic reaction. These findings suggest that diet-related inflammation might contribute to development of colorectal cancer, by suppressing the adaptive anti-tumor immune response.

中文翻译：

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炎症性饮食模式与按肿瘤免疫反应分类的结直肠癌亚型风险之间的关联

 背景与目标

饮食模式影响全身和局部肠道炎症，这与结直肠癌的发生有关。慢性炎症会干扰适应性免疫反应。我们研究了对于淋巴细胞反应较低的肿瘤，促进肠道炎症的饮食与结直肠癌风险之间的关联是否比淋巴细胞反应较高的肿瘤更强。

 方法

我们从 2 项前瞻性队列研究的分子病理流行病学数据库中收集了数据：护士健康研究（自 1976 年以来）和卫生专业人员随访研究（自 1986 年以来）。我们使用重复法时变 Cox 比例特定风险回归来评估经验饮食炎症模式 (EDIP) 评分（源自食物频率问卷数据）与结直肠癌亚型的关联。有助于获得高 EDIP 分数的食物包括红肉和加工肉类、精制谷物、碳酸饮料和一些蔬菜；导致 EDIP 分数较低的食物包括啤酒、葡萄酒、咖啡、茶、黄叶蔬菜和果汁。对结直肠组织样本进行组织学分析，了解淋巴细胞反应的模式（克罗恩病样淋巴细胞反应、瘤周淋巴细胞反应、瘤内腺周反应和肿瘤浸润淋巴细胞）。

 结果

在对 124,433 名参与者进行随访期间，我们利用可用的组织数据记录了 1311 例结肠癌和直肠癌病例。 EDIP 与结直肠癌风险之间的相关性显着（ P_趋势= .02），并且随瘤周淋巴细胞反应程度的不同而变化（ P_异质性< .001）。较高的 EDIP 评分与肿瘤周围淋巴细胞反应缺失或较低的结直肠癌风险增加相关（最高与最低 EDIP 评分五分位数风险比，2.60；95% 置信区间，1.60−4.23； P_趋势< .001），但并非如此具有中等或高度瘤周淋巴细胞反应的肿瘤风险（ P_趋势> .80）。

 结论

在两项前瞻性队列研究中，我们将炎症饮食与结直肠癌亚型的较高风险相关联，该亚型几乎没有或没有瘤周淋巴细胞反应。这些发现表明，与饮食相关的炎症可能通过抑制适应性抗肿瘤免疫反应而导致结直肠癌的发生。