Interactions of multi-target stool DNA, intestinal flora, carcinoembryonic antigen and fruit intake on the risk of colorectal cancer
GAO Hanlu1, YU Xiaofang2, LÜ Lebin3, YE Guoliang2, FAN Jinqing2
1. Department of Preventive Care, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315000, China; 2. The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315000, China; 3. Ningbo University, Ningbo, Zhejiang 315000, China
Abstract：Objective To explore the interaction of multi-target stool DNA (MT-sDNA), intestinal flora and environmental factors in the development of colorectal cancer, so as to provide insights into pathogenesis study of colorectal cancer. Methods A total of 54 cases of colorectal cancer from the First Affiliated Hospital of Ningbo University were included 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 antigen 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 dimensionality 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 >5 μg/L of CEA had an increased 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.
[1] 陈奇峰,陈康康,李金,等. 2011—2019年绍兴市结直肠癌发病趋势分析[J].预防医学,2021,33(11):1146-1148. [2] CHEN H D,LI N,SHI J F,et al. Comparative evaluation of novel screening strategies for colorectal cancer screening in China(TARGET-C):a study protocol for a multicentre randomised controlled trial[J/OL]. BMJ Open,2019,9(4)[2023-09-12]. https://doi.org/10.1136/bmjopen-2018-025935. [3] ANAND S,LIANG P S.A practical overview of the stool DNA test for colorectal cancer screening[J]. Clin Transl Gastroenterol,2022,13(4):1-4. [4] 吕乐彬,樊金卿,赵王芳,等.肠镜检查人群多靶点粪便DNA检测意愿的影响因素分析[J].预防医学,2023,35(3):218-223. [5] ZHAO L Y,ZHANG X,ZUO T,et al.The composition of colonic commensal bacteria according to anatomical localization in colorectal cancer[J]. Engineering,2017,10(3):90-97. [6] TILG H,ADOLPH T E,GERNER R R,et al.The intestinal microbiota in colorectal cancer[J]. Cancer Cell,2018,33(6):954-964. [7] GAO R Y,ZHU Y F,KONG C,et al.Alterations,interactions,and diagnostic potential of gut bacteria and viruses in colorectal cancer[J]. Front Cell Infect Microbiol,2021,11:1-13. [8] SHEN W T,TANG D R,WAN P,et al.Identification of tissue-specific microbial profile of esophageal squamous cell carcinoma by full-length 16S rDNA sequencing[J]. Appl Microbiol Biotechnol,2022,106(8):3215-3129. [9] JIN P,YOU P,FANG J Y,et al.Comparison of performance of two stool DNA tests and a fecal immunochemical test in detecting colorectal neoplasm:a multicenter diagnostic study[J]. Cancer Epidemiol Biomarkers Prev,2022,31:654-661. [10] XU H L,CHEN H X,HU J J,et al.Feasibility of quantification based on novel evaluation with stool DNA and fecal immunochemical test for colorectal cancer detection[J]. BMC Gastroenterol,2022,22(1):1-8. [11] DOUGLAS G M,MAFFEI V J,ZANEVELD J R,et al.PICRUSt2 for prediction of metagenome functions[J]. Nat Biotechnol,2020,38(6):685-688. [12] GAO H L,LV L B,ZHAO W F,et al.Diagnostic accuracy of the multi-target stool DNA test in detecting colorectal cancer:a hospital-based study[J]. World J Gastrointest Oncol,2023,15(1):102-111. [13] FAN J Q,ZHAO W F,LU Q W,et al.Fecal microbial biomarkers along with multi-target stool DNA improve the diagnostic accuracy in colorectal cancer[J]. World J Gastrointest Oncol,2023,15(8):1424-1435. [14] SONG M,CHAN A T,SUN J.Influence of the gut microbiome,diet,and environment on risk of colorectal cancer[J]. Gastroenterology,2020,158(2):322-340. [15] KENKHUIS M F,VAN DUIJNHOVEN F J B,VAN ROEKEL E H,et al. Longitudinal associations of fiber,vegetable,and fruit intake with quality of life and fatigue in colorectal cancer survivors up to 24 months posttreatment[J]. Am J Clin Nutr,2022,115(3):822-832. [16] TAHA H M,SLADE A N,SCHWARTZ B,et al.A case-control study examining the association of fiber,fruit,and vegetable intake and the risk of colorectal cancer in a Palestinian population[J]. Int J Environ Res Public Health,2022,19(12):1-11. [17] CAO X,YU G X,REN W,et al.DualWMDR:detecting epistatic interaction with dual screening and multifactor dimensionality reduction[J]. Hum Mutat,2020,41(3):719-734.
