Pre-diagnostic anthropometry, sex, and risk of colorectal cancer according to tumor immune cell composition
Pre-diagnostic anthropometry, sex, and risk of colorectal cancer according to tumor immune cell composition
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DOI：
10.1080/2162402x.2019.1664275
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发表时间：
2019-09-21
期刊：
影响因子：
7.2
通讯作者：
Jirstroem, Karin
中科院分区：
文献类型：
--
作者：
Berntsson, Jonna;Eberhard, Jakob;Jirstroem, Karin
肥胖是结直肠癌（CRC）的一个公认的危险因素，但与肿瘤微环境的关联很少被描述。在此，我们根据肿瘤免疫细胞组成，特别是潜在的性别差异，研究了诊断前人体测量与CRC风险之间的关系。在一个前瞻性的、基于人群的队列（n = 28098）中，通过免疫组织化学在584例CRC病例的肿瘤组织微阵列中评估不同免疫细胞亚群的密度。应用多变量考克斯回归模型（根据年龄、吸烟、饮酒和教育水平进行调整）来计算与诊断前身高、体重、体重指数（BMI）四分位数相关的免疫标志物定义的CRC的风险。腰围和臀围、腰臀比（WHR）和体脂百分比（BFP）。肥胖与CRC风险显著相关，FoxP 3（+）T细胞密度低，肿瘤细胞上程序性细胞死亡蛋白1（PD-L1）表达低，但CD 8（+）T细胞和CD 20（+）B细胞密度高。在女性中，肥胖与PD-L1高肿瘤风险显著相关（体重p= 0.009，BMI p= 0.039）。相比之下，在男性中，所有人体测量因素定义的肥胖与PD-L1低肿瘤显著相关（体重p= 0.005，BMI p = 0.002，
Obesity is a well-established risk factor for colorectal cancer (CRC), but the association with the tumor microenvironment has been sparsely described. Herein, we examined the relationship between pre-diagnostic anthropometry and CRC risk according to tumor immune cell composition, with particular reference to potential sex differences. The density of different immune cell subsets was assessed by immunohistochemistry in tissue microarrays with tumors from 584 incident CRC cases in a prospective, population-based cohort (n = 28098). Multivariable Cox regression models, adjusted for age, smoking, alcohol intake, and educational level, were applied to calculate risk of immune marker-defined CRC in relation to quartiles of pre-diagnostic height, weight, body mass index (BMI), waist and hip circumferences, waist-hip ratio (WHR), and body fat percentage (BFP). Obesity was all over significantly associated with risk of CRC with low density of FoxP3(+) T cells and low programmed cell-death protein 1 (PD-L1) expression on tumor cells, but with high density of CD8(+) T cells and CD20(+) B cells. In women, obesity was significantly associated with risk of PD-L1 high tumors (p= 0.009 for weight, p= 0.039 for BMI). Contrastingly, in men, obesity defined by all anthropometric factors was significantly associated with PD-L1 low tumors (p= 0.005 for weight, p = 0.002 for BMI, p