Data from The Effect of Metformin in Treatment of Adenomas in Patients with Familial Adenomatous Polyposis
Jae Jun ParkByung Chang KimSung Pil HongYoojeong SeoHye Sun LeeYoung Sook ParkSoo‐Young NaSung Chul ParkJongha ParkJae Hak KimChang Mo MoonKyu Chan HuhSoo Jung ParkJae Hee CheonWon Ho KimTae Il Kim
0
Citation
0
Reference
10
Related Paper
Abstract:
<div>Abstract<p>Familial adenomatous polyposis (FAP) is a hereditary disease characterized by the development of numerous colorectal adenomas in young adults. Metformin, an oral diabetic drug, has been shown to have antineoplastic effects and a favorable safety profile. We performed a randomized, double-blind, controlled trial to evaluate the efficacy of metformin on the regression of colorectal and duodenal adenoma in patients with FAP. Thirty-four FAP patients were randomly assigned in a 1:2:2 ratio to receive placebo, 500 mg metformin, or 1,500 mg metformin per day orally for 7 months. The number and size of polyps and the global polyp burden were evaluated before and after the intervention. This study was terminated early based on the results of the interim analysis. No significant differences were determined in the percentage change of colorectal and duodenal polyp number over the course of treatment among the three treatment arms (<i>P</i> = 0.627 and <i>P</i> = 1.000, respectively). We found no significant differences in the percentage change of colorectal or duodenal polyp size among the three groups (<i>P</i> = 0.214 and <i>P</i> = 0.803, respectively). The overall polyp burdens of the colorectum and duodenum were not significantly changed by metformin treatment at either dosage. Colon polyps removed from the metformin-treated patients showed significantly lower mTOR signal (p-S6) expression than those from patients in the placebo arm. In conclusion, 7 months of treatment with 500 mg or 1,500 mg metformin did not reduce the mean number or size of polyps in the colorectum or duodenum in FAP patients (ClinicalTrials.gov ID: NCT01725490).</p>Prevention Relevance:<p>A 7-month metformin treatment (500 mg or 1,500 mg) did not reduce the number or size of polyps in the colorectum or duodenum of FAP patients as compared to placebo. These results do not support the use of metformin to promote regression of intestinal adenomas in FAP patients.</p></div>Keywords:
Colorectal adenoma
Duodenal adenomas are common in familial adenomatous polyposis (FAP). It is, however, not known whether patients with duodenal adenomas without FAP should undergo routine colonoscopy for detection of colorectal neoplasia. The aim of this study was to evaluate the correlation between the incidence of sporadic duodenal adenomas and colorectal neoplasias.Patients with sporadic duodenal adenomas and without FAP were retrospectively evaluated for the existence of colorectal neoplasia. Each patient was compared with three randomly selected age and sex-matched controls.Sporadic duodenal adenomas were diagnosed by endoscopy in 51 patients, of whom 48 underwent additional colonoscopy. The mean age of the 48 analysed patients was 66 (40-83) years (women:men=23 : 25). Colorectal neoplasia was significantly more common among patients with duodenal adenomas (75% vs. 27.7%; P<0.05; odds ratio=7.80 [95% confidence interval 3.48-17.72]).In this case control study, the prevalence of colorectal adenomas in patients with sporadic duodenal adenomas without FAP was significantly increased compared with the average population. Therefore, patients with duodenal adenomas should be screened for the occurrence of colorectal adenomas.
Colorectal adenoma
Cite
Citations (15)
Colorectal adenoma
Cite
Citations (8)
Objective To investigate the changes of PGE2 in the tissues of ulcerative colitis,colon adenoma and colon cancer,and the effect of aspirin on postoperative recurrence of the diseases. Methods PGE2 levels in homogenate of ulcerative colitis,colon adenoma and colon cancer were determined with radioimmune assay.Patients underwent surgery for colon adenoma and cancer were divided into aspirin-treatment group and placebo group.Both were followed for six months. Results Preoperatively,the PGE2 in colitis,adenoma and cancer tissues were(143.40±18.32),(184.52±21.21),and(242.43±23.40)ng/g,respectively,with significant difference among these three groups(F=278.52,q=13.79-33.22,P0.05).The recurrence at six months after operation was significantly lower in aspirin group than that of the placebo(χ2=5.38,P0.05). ConclusionThere is a tendency of increasing PGE2 level in tissue of colon cancer.Aspirin shows a definite prevention of recurrence of colon adenoma and colon cancer,postoperatively.
Colorectal adenoma
Cite
Citations (0)
Colorectal cancer (CRC) is one of the most common neoplasia in Western countries and the second leading cause of cancer-related death. The vast majority of cases belong to sporadic forms, whereas a small but relevant proportion of them corresponds to inherited disorders, i.e. familial adenomatous polyposis and Lynch syndrome. These individuals with germline mutations in cancer-promoting genes, along with those who had already developed a colorectal neoplasm, either adenoma or carcinoma, stand to benefit from chemopreventive interventions. A large body of evidence indicates that the use of aspirin and other non-steroidal anti-inflammatory drugs (NSAID) can reduce the risk of CRC. Experimental studies have demonstrated that these drugs decrease the incidence of carcinogen-induced colon tumors in rodents, and several epidemiological investigations and therapeutic trials have also shown a 40-50% reduction in the risk of colorectal adenoma and cancer in individuals taking NSAIDs. Moreover, patients with familial adenomatous polyposis taking sulindac or celecoxib experience a reduction in adenoma size and number. The chemopreventive effects of NSAID are largely related to inhibition of cyclooxygenase-2 (COX-2), the inducible isoform of cyclooxygenase that catalyzes the conversion of arachidonic acid to prostaglandins. COX-2 overexpression is a frequent, but not universal event in colorectal neoplasms. Indeed, approximately 50% of adenomas and 80% of CRC express high levels of COX-2 mRNA and protein in neoplastic tissue. In this article, we will review the role of cyclooxygenase as a target for CRC chemoprevention, with special attention to the use of selective and non-selective COX-2 inhibitors in both individuals genetically predisposed and those who have already developed a colorectal neoplasm. Keywords: colorectal neoplasms, non-steroidal anti-inflammatory drugs, NSAID, chemoprevention, COX-2 inhibitors, prevention, cyclooxygenase, apoptosis, lynch syndrome, angiogenesis
Colorectal adenoma
Lynch Syndrome
Sulindac
Celecoxib
Cite
Citations (56)
Loss of APC is an initial, rate-limiting event in inherited and sporadic colorectal tumorigenesis. Rare germline APC mutations have been identified in patients with multiple colorectal adenomas. Recently, the E1317Q APC variant has been associated with a predisposition to the development of multiple colorectal adenomas. In this study, the prevalence of the E1317Q variant was examined in 182 patients with single or multiple colorectal adenomas, and in 235 controls. In all, E1317Q was identified in two of 182 patients with adenomatous polyps (1.1%) and in two of 235 controls (0.8%) (p = 0.59). The risk of harboring adenoma(s) among subjects bearing the E1317Q variant was 1.29 (95% CI 0.09–18.0). No difference in the prevalence of E1317Q between cases with single (2.0%) or multiple colorectal adenomas (0.7%) and controls (0.8%) was found. None of the subjects with a family history of colorectal cancer carried the E1317Q variant. In conclusion, our results confirm that only a very small fraction of colorectal adenomas may be associated with the presence of E1317Q.
Colorectal adenoma
Adenomatous polyposis coli
Cite
Citations (18)
Background/Aims Colorectal cancer (CRC) develops from colonic adenomas. Type 2 diabetes mellitus (DM) is associated with a higher risk of CRC and metformin decreases CRC risk. However, it is not certain if metformin affects the development of colorectal polyps and adenomas. This study aimed to elucidate if metforminaffects the incidence of colonic polyps and adenomas in patients with type 2 DM. Methods Of 12,186 patients with type 2 DM, 3,775 underwent colonoscopy between May 2001 and March 2013. This study enrolled 3,105 of these patients, and divided them in two groups: 912 patients with metformin use and 2,193 patients without metformin use. Patient clinical characteristics, polyp and adenoma detection rate in the two groups were analyzed retrospectively. Results The Colorectal polyp detection rate was lower in the metformin group than in the non-meformin group (39.4% vs. 62.4%, P<0.01). Colorectal adenoma detection rate was significantly lower in the metformin group than in the non-metformin group (15.2% vs. 20.5%, P<0.01). Fewer advanced adenomas were detected in the metformin group than in the non-metformin group (12.2% vs. 22%, P<0.01). Multivariate analysis identified age, sex, Body mass index and metformin use as factors associated with polyp incidence, whereas only metforminwas independently associated with decreased adenoma incidence (Odd ratio=0.738, 95% CI=0.554-0.983, P=0.03). Conclusions In patients with type 2 DM, metformin reduced the incidence of adenomas that may transform into CRC. Therefore, metformin may be useful for the prevention of CRC in patients with type 2 DM. Keywords: Colon adenoma; Adenoma detection rate; Polyp detection rate; Metformin; Diabetes mellitus, type 2
Colorectal adenoma
Cite
Citations (32)
Polypectomy
Colorectal adenoma
Cite
Citations (38)
Colorectal cancer, arising from colorectal adenoma, remains a common cancer and cause of death in men and women. Currently there are many developments in modern surgery and chemo-radiotherapy, including screening and prevention programmes, aimed to increase survival time. This article briefly reviews the role of chemopreventive agents in colorectal cancer. Regular aspirin use reduces the risk of sporadic colorectal adenomas. Sulindac and celecoxib (nonsteroidal antiinflammatory drugs, NSAIDs) reduce the number and size of colorectal adenomas in patients with familial adenomatous polyposis. Folate, calcium, hormone-replacement therapy, vitamins, antioxidants and dietary fiber intake might contribute to the prevention of colorectal adenomas and carcinomas; however further randomized controlled trials are needed to support this theory.
Cite
Citations (0)
Familial adenomatous polyposis (FAP) is a hereditary disease characterized by the development of numerous colorectal adenomas in young adults. Metformin, an oral diabetic drug, has been shown to have antineoplastic effects and a favorable safety profile. We performed a randomized, double-blind, controlled trial to evaluate the efficacy of metformin on the regression of colorectal and duodenal adenoma in patients with FAP. Thirty-four FAP patients were randomly assigned in a 1:2:2 ratio to receive placebo, 500 mg metformin, or 1,500 mg metformin per day orally for 7 months. The number and size of polyps and the global polyp burden were evaluated before and after the intervention. This study was terminated early based on the results of the interim analysis. No significant differences were determined in the percentage change of colorectal and duodenal polyp number over the course of treatment among the three treatment arms (P = 0.627 and P = 1.000, respectively). We found no significant differences in the percentage change of colorectal or duodenal polyp size among the three groups (P = 0.214 and P = 0.803, respectively). The overall polyp burdens of the colorectum and duodenum were not significantly changed by metformin treatment at either dosage. Colon polyps removed from the metformin-treated patients showed significantly lower mTOR signal (p-S6) expression than those from patients in the placebo arm. In conclusion, 7 months of treatment with 500 mg or 1,500 mg metformin did not reduce the mean number or size of polyps in the colorectum or duodenum in FAP patients (ClinicalTrials.gov ID: NCT01725490). PREVENTION RELEVANCE: A 7-month metformin treatment (500 mg or 1,500 mg) did not reduce the number or size of polyps in the colorectum or duodenum of FAP patients as compared to placebo. These results do not support the use of metformin to promote regression of intestinal adenomas in FAP patients.
Colorectal adenoma
Cite
Citations (14)
Familial risk factors are known to play an important role in colorectal cancer (CRC) risk, particularly when the relatives are affected by early-onset cancer. Part of this familial aggregation can be accounted for by inherited forms of colorectal cancer, i.e. familial adenomatous polyposis (less than 1% of all CRC) and hereditary nonpolyposis colorectal cancer (about 3%). Other genetic factors may be involved in the development of adenoma or in the transformation of adenoma into carcinoma. That the existence of polymorphisms of the adenomatous polyposis coli gene increase susceptibility to both adenomas and cancer favours this hypothesis. Interactions between environmental factors, and most of all dietary factors, and polymorphisms of carcinogen-metabolizing enzymes may also be involved. Better knowledge of these mechanisms will substantially widen the scope of colorectal cancer prevention.
Colorectal adenoma
Adenomatous polyposis coli
Family aggregation
Cite
Citations (21)