Adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations and WNT-pathway-related markers of bowel cancer risk.
Adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations and WNT-pathway-related markers of bowel cancer risk.
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DOI：
10.1017/s0007114518002520
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发表时间：
2019-09-14
期刊：
影响因子：
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通讯作者：
Mathers JC
中科院分区：
文献类型：
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作者：
Malcomson FC;Willis ND;McCallum I;Xie L;Kelly S;Bradburn DM;Belshaw NJ;Johnson IT;Mathers JC
肠癌风险受生活方式因素的强烈影响，包括饮食和体育活动。一些研究调查了遵守WCRF/AICR癌症预防建议对全因和癌症特异性死亡率等结局的影响，但与肠癌风险影响的分子机制之间的关系尚不清楚。本研究旨在探讨遵循WCRF/AICR癌症预防建议与WNT通路相关的肠癌风险标志物之间的关系，包括WNT通路基因和调节性miRNA的表达，结直肠粘膜活检中SFRP 1甲基化和结肠隐窝增殖状态。作为DISC研究的一部分，使用了75名健康参与者的饮食和生活方式数据。设计了一个评分系统，包括七个癌症预防建议和吸烟状况。分别使用斯皮尔曼等级相关分析和非配对t检验评估总依从性评分和个人建议评分对测量结果的影响。总粘附评分与c-MYC（p=0.039）和WNT 11（p=0.025）的表达呈负相关，高粘附者CCND 1（p=0.042）、WNT 11（p=0.012）和c-MYC（p=0.048）的表达显著降低。AXIN 2、GSK 3 β、CTNNB 1和WNT 11以及致癌miRNA miR-17的表达和结肠隐窝动力学与个体推荐评分显著相关，包括体脂、红肉摄入量、植物性食物摄入量和吸烟状况。这项研究的结果为遵循WCRF/AICR癌症预防建议对肠癌风险的WNT途径相关标志物的积极影响提供了证据。
Bowel cancer risk is strongly influenced by lifestyle factors including diet and physical activity. Several studies have investigated the effects of adherence to the WCRF/AICR cancer prevention recommendations on outcomes such as all-cause and cancer-specific mortality, but the relationships with molecular mechanisms that underlie the effects on bowel cancer risk are unknown. This study aimed to investigate the relationships between adherence to the WCRF/AICR cancer prevention recommendations and WNT pathway-related markers of bowel cancer risk, including the expression of WNT pathway genes and regulatory miRNAs, SFRP1 methylation and colonic crypt proliferative state in colorectal mucosal biopsies. Dietary and lifestyle data from 75 healthy participants recruited as part of the DISC Study were used. A scoring system was devised including seven of the cancer prevention recommendations and smoking status. The effects of total adherence score and scores for individual recommendations on the measured outcomes were assessed using Spearman’s rank correlation analysis and unpaired t-tests, respectively. Total adherence score correlated negatively with expression of c-MYC (p=0.039) and WNT11 (p=0.025) and high-adherers had significantly reduced expression of CCND1 (p=0.042), WNT11 (p=0.012) and c-MYC (p=0.048). Expression of AXIN2, GSK3β, CTNNB1 and WNT11 and of the oncogenic miRNA miR-17 and colonic crypt kinetics correlated significantly with scores for individual recommendations, including body fatness, red meat intake, plant food intake and smoking status. The findings from this study provide evidence for positive effects of adherence to the WCRF/AICR cancer prevention recommendations on WNT pathway-related markers of bowel cancer risk.