Analysis Of Risk Factors For Canceration Of Familial Adenomatous Polyposis And Clinical Significance Of Related Germline Gene Mutation

Objective:To explore the risk factors of familial adenomatous polyposis(FAP)carcinogenesis,analyze the relationship between FAP carcinogenesis and the patient’s gender,lifestyle,age of onset,number of adenomas,adenoma diameter,combined extraintestinal manifestations,histological type of adenoma,and family history At the same time,analyze the clinicopathological characteristics of FAP cancer patients and sporadic colorectal cancer patients and the germline mutations of APC,MUTYH,MSH3,POLD1,and POLE genes.Methods:From September 2009 to September 2019,21 patients with familial adenomatous polyposis who underwent total or partial colectomy(14 patients with canceration and7 patients without canceration)and 16 patients with sporadic colorectal cancer who had no family polyp history and cancer-related history were selected as the research objects.Objective to analyze the relationship between the clinicopathological features of FAP patients with canceration and non canceration,FAP patients with canceration and sporadic colorectal cancer.The APC,MUTYH,MSH3,pold1 and pole germline genes were detected by Illumina hiseq 4000 high-throughput sequencing platform to detect the specific gene mutation and mutation abundance of each patient.Results:1.Among the 21 patients with FAP,14 cases were diagnosed with cancer,including 9 males and 5 females.The overall cancer rate was 66.67%.The average age was(46.28 ± 11.84)years(range,27-69 years).9 cases(42.88%)were complicated with gastric polyps,1 case(4.76%)with duodenal polyps,1 case(4.76%)with lipoma,1 case(4.76%)with thyroid cancer and 1 case(4.76%)with Brenner tumor of ovary.2.In 16 cases of sporadic colorectal cancer,there were 8 males and 8 females,aged from 38 to 84 years,with an average age of 62.38 ± 12.27 years.One case 9(6.25%)had gastric polyps.3.Univariate analysis showed that the number of adenomas was different(P =0.02 < 0.05)and the size of adenomas was different(P = 0.001 < 0.05).There was significant difference between the cancerous group and the non cancerous group(P =0.02 < 0.05).4.Univariate analysis showed that FAP canceration group was significantly different from sporadic colorectal cancer in age(P = 0.002 < 0.05),tumor size(P =0.041 < 0.05),N stage,TNM clinical stage,extraintestinal manifestations(P = 0.031 <0.05)and lymph node metastasis(P = < 0.001).5.The germline mutations of APC,MUTYH,MSH3,pold1 and pole genes were detected in all patients.Only APC gene had germline mutations.Seventeen cases(17 /21,80.95%)of FAP patients had germline mutations of APC gene,including 11 cases(11 / 17,64.71%)of cancer patients.Two cases(2 / 16,12.5%)had germline mutation of APC gene in sporadic colon cancer.6.There was no germ line mutation in APC gene,and there was significant difference between FAP and sporadic colorectal cancer(P = 0.001 < 0.05).Conclusions:1.The number and size of adenoma are related factors of FAP carcinogenesis,and they are positively correlated.Therefore,for patients with large diameter and large number of adenomas,preventive treatment should be carried out in time to prevent canceration.2.The age of canceration in patients with FAP is earlier than that in patients with sporadic colorectal cancer,and the clinical stage is later.3.Germline mutation of APC gene can lead to familial adenomatous polyposis,so molecular screening and monitoring of APC gene are feasible for patients with suspected FAP.4.There is no correlation between the related germline genes and the canceration rate of familial adenomatous polyposis.