多靶点粪便DNA、肠道菌群、癌胚抗原及水果摄入对结直肠癌风险的交互作用研究

Interactions of multi-target stool DNA,intestinal flora,carcinoembryonic antigen and fruit intake on the risk of colorectal cancer

目的探讨多靶点粪便DNA(MT-sDNA)、肠道菌群及饮食等环境因素之间的交互作用以及对结直肠癌的影响,为结直肠癌发病机制研究提供依据。方法选择宁波大学附属第一医院结直肠癌病例54例纳入病例组,同期健康体检者51人纳入对照组,通过问卷调查收集人口学信息、饮食和结直肠癌家族史等资料;检测MT-sDNA、肠道菌群,以及癌抗原19-9、癌胚抗原(CEA)等肿瘤标志物;采用多因子降维法、叉生分析法和相加交互作用模型分析MT-sDNA、肠道菌群、环境因素的交互作用对结直肠癌患病的影响。结果病例组年龄为(64.89±9.72)岁,男性20例,占37.04%,女性34例,占62.96%;对照组年龄为(53.94±10.33)岁,男性24人,占47.06%,女性27人,占52.94%。多因子降维法分析结果显示,同时有肠道菌群指数绝对值偏高和MT-sDNA阳性的人群患结直肠癌的风险较高(OR=3.782,95%CI:1.190~5.034)。叉生分析结果显示,MT-sDNA阳性与CEA>5μg/L的人群患结直肠癌的风险较高(OR=2.121,95%CI:1.162~4.033)。相加模型分析结果显示,MT-sDNA与CEA存在正相加交互作用(SI=3.687,95%CI:1.229~7.238),MT-sDNA与吃水果存在负相加交互作用(SI=0.145,95%CI:0.020~0.753)。结论MT-sDNA阳性可与肠道菌群指数偏高或CEA联合增加结直肠癌风险,吃水果可减少MT-sDNA阳性人群的结直肠癌风险。

Objective To explore the interaction of multi-target stool DNA(MT-sDNA),intestinal flora and environmen⁃tal factors in the development of colorectal cancer,so as to provide insights into pathogenesis study of colorectal can⁃cer.Methods A total of 54 cases of colorectal cancer from the First Affiliated Hospital of Ningbo University were in⁃cluded in the case group and 51 healthy subjects were included in the control group.Demographic information,diet and family history of colorectal cancer were collected by a questionnaire survey.MT-sDNA,intestinal flora,cancer anti⁃gen 19-9(CA19-9),carcinoembryonic antigen(CEA)and other tumor markers were detected.Interactions of MT-sDNA,intestinal flora and environmental factors with the development of colorectal cancer was analyzed by multifactor dimen⁃sionality reduction(MDR),crossover analysis and additive model.Results The case group included 20 males(37.04%)and 34 females(62.96%),and had a mean age of(64.89±9.72)years.The control group included 24 males(47.06%)and 27 females(52.94%),and had a mean age of(53.94±10.33)years.MDR analysis showed that subjects with both high absolute intestinal flora indexes and positive MT-sDNA had an increased risk of colorectal cancer(OR=3.782,95%CI:1.190-5.034).Crossover analysis showed that subjects with positive MT-sDNA and>5μg/L of CEA had an in⁃creased risk of colorectal cancer(OR=2.121,95%CI:1.162-4.033).Additive model analysis showed that MT-sDNA had positive additive interaction with CEA(SI=3.687,95%CI:1.229-7.238),and MT-sDNA had negative additive interaction with fruit intake(SI=0.145,95%CI:0.020-0.753).Conclusion Positive MT-sDNA can synergistically increase the risk of colorectal cancer with high intestinal flora index and CEA,and fruit intake can reduce the risk of colorectal cancer in MT-sDNA-positive population.