Hanyuda Akiko, Cao Yin, Hamada Tsuyoshi, Nowak Jonathan A, Qian Zhi Rong, Masugi Yohei, da Silva Annacarolina, Liu Li, Kosumi Keisuke, Soong Thing Rinda, Jhun Iny, Wu Kana, Zhang Xuehong, Song Mingyang, Meyerhardt Jeffrey A, Chan Andrew T, Fuchs Charles S, Giovannucci Edward L, Ogino Shuji, Nishihara Reiko
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
Eur J Epidemiol. 2017 May;32(5):393-407. doi: 10.1007/s10654-017-0254-y. Epub 2017 May 16.
Previous studies suggest that abnormal energy balance status may dysregulate intestinal epithelial homeostasis and promote colorectal carcinogenesis, yet little is known about how host energy balance and obesity influence enterocyte differentiation during carcinogenesis. We hypothesized that the association between high body mass index (BMI) and colorectal carcinoma incidence might differ according to tumor histopathologic differentiation status. Using databases of the Nurses' Health Study and Health Professionals Follow-up Study, and duplication-method Cox proportional hazards models, we prospectively examined an association between BMI and the incidence of colorectal carcinoma subtypes classified by differentiation features. 120,813 participants were followed for 26 or 32 years and 1528 rectal and colon cancer cases with available tumor pathological data were documented. The association between BMI and colorectal cancer risk significantly differed depending on the presence or absence of poorly-differentiated foci (P = 0.006). Higher BMI was associated with a higher risk of colorectal carcinoma without poorly-differentiated foci (≥30.0 vs. 18.5-22.4 kg/m: multivariable-adjusted hazard ratio, 1.87; 95% confidence interval, 1.49-2.34; P < 0.001), but not with risk of carcinoma with poorly-differentiated foci (P = 0.56). This differential association appeared to be consistent in strata of tumor microsatellite instability or FASN expression status, although the statistical power was limited. The association between BMI and colorectal carcinoma risk did not significantly differ by overall tumor differentiation, mucinous differentiation, or signet ring cell component (P > 0.03, with the adjusted α of 0.01). High BMI was associated with risk of colorectal cancer subtype containing no poorly-differentiated focus. Our findings suggest that carcinogenic influence of excess energy balance might be stronger for tumors that retain better intestinal differentiation throughout the tumor areas.
先前的研究表明，能量平衡异常状态可能会破坏肠道上皮内稳态并促进结直肠癌发生，然而，关于宿主能量平衡和肥胖如何在致癌过程中影响肠上皮细胞分化，人们却知之甚少。我们推测，高体重指数（BMI）与结直肠癌发病率之间的关联可能因肿瘤组织病理学分化状态而异。利用护士健康研究和卫生专业人员随访研究的数据库，以及重复法Cox比例风险模型，我们前瞻性地研究了BMI与根据分化特征分类的结直肠癌亚型发病率之间的关联。120813名参与者被随访了26或32年，记录了1528例有可用肿瘤病理数据的直肠癌和结肠癌病例。BMI与结直肠癌风险之间的关联因是否存在低分化灶而有显著差异（P = 0.006）。较高的BMI与无低分化灶的结直肠癌风险较高相关（≥30.0 vs. 18.5 - 22.4 kg/m²：多变量调整风险比，1.87；95%置信区间，1.49 - 2.34；P < 0.001），但与有低分化灶的癌症风险无关（P = 0.56）。尽管统计效能有限，但这种差异关联在肿瘤微卫星不稳定性或FASN表达状态分层中似乎是一致的。BMI与结直肠癌风险之间的关联在总体肿瘤分化、黏液分化或印戒细胞成分方面无显著差异（P > 0.03，调整后的α为0.01）。高BMI与不含低分化灶的结直肠癌亚型风险相关。我们的研究结果表明，对于在整个肿瘤区域保持较好肠道分化的肿瘤，能量平衡过剩的致癌影响可能更强。
