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炎症性饮食模式与根据肿瘤免疫反应分类的结直肠癌亚型风险之间的关联。

Association Between Inflammatory Diet Pattern and Risk of Colorectal Carcinoma Subtypes Classified by Immune Responses to Tumor.

作者信息

Liu Li, Nishihara Reiko, Qian Zhi Rong, Tabung Fred K, Nevo Daniel, Zhang Xuehong, Song Mingyang, Cao Yin, Mima Kosuke, Masugi Yohei, Shi Yan, da Silva Annacarolina, Twombly Tyler, Gu Mancang, Li Wanwan, Hamada Tsuyoshi, Kosumi Keisuke, Inamura Kentaro, Nowak Jonathan A, Drew David A, Lochhead Paul, Nosho Katsuhiko, Wu Kana, Wang Molin, Garrett Wendy S, Chan Andrew T, Fuchs Charles S, Giovannucci Edward L, Ogino Shuji

机构信息

Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

出版信息

Gastroenterology. 2017 Dec;153(6):1517-1530.e14. doi: 10.1053/j.gastro.2017.08.045. Epub 2017 Sep 1.

Abstract

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 = .02), and varied with degree of peritumoral lymphocytic reaction (P < .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 < .001), but not risk of tumors with intermediate or high peritumoral lymphocytic reaction (P > .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.

摘要

背景与目的

饮食模式会影响全身和局部肠道炎症,而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。我们研究了促进肠道炎症的饮食与结直肠癌风险之间的关联,对于淋巴细胞反应较低的肿瘤,这种关联是否比淋巴细胞反应较高的肿瘤更强。

方法

我们从两项前瞻性队列研究的分子病理流行病学数据库中收集数据:护士健康研究(自1976年起)和卫生专业人员随访研究(自1986年起)。我们使用重复法时变Cox比例特定病因风险回归来评估经验性饮食炎症模式(EDIP)评分(源自食物频率问卷数据)与结直肠癌亚型之间的关联。导致EDIP评分高的食物包括红肉和加工肉类、精制谷物、碳酸饮料以及一些蔬菜;导致EDIP评分低的食物包括啤酒、葡萄酒、咖啡、茶、黄色和叶菜类蔬菜以及果汁。对结直肠组织样本进行组织学分析,以观察淋巴细胞反应模式(克罗恩样淋巴样反应、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名参与者的随访期间,我们记录了1311例有可用组织数据的结肠癌和直肠癌病例。EDIP与结直肠癌风险之间的关联具有显著性(P = 0.02),并且随瘤周淋巴细胞反应程度而变化(P < 0.001)。EDIP评分较高与瘤周淋巴细胞反应缺失或较低的结直肠癌风险增加相关(EDIP评分最高五分位数与最低五分位数的风险比,2.60;95%置信区间,1.60 - 4.23;P < 0.001),但与瘤周淋巴细胞反应中等或较高的肿瘤风险无关(P > 0.80)。

结论

在两项前瞻性队列研究中,我们发现炎症性饮食与瘤周淋巴细胞反应很少或没有的结直肠癌亚型风险较高相关。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,促进结直肠癌的发生。

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