The role of mismatch repair gene defects in the development of adenomas in patients with HNPCC

BACKGROUND AND AIMS: The adenoma-carcinoma sequence in hereditary nonpolyposis colorectal cancer (HNPCC) is accelerated. It remains unknown whether the mismatch repair (MMR) defect also promotes the development of adenomas. The aim of this study was to compare the risk of developing colorectal adenoma and carcinoma in HNPCC carriers and noncarriers (controls) and to compare the features of adenomas in both groups. METHODS: Eighty-six families with a known MMR gene mutation from the Dutch HNPCC Registry were analyzed. Subjects with known mutation status with colonoscopies performed for the purpose of surveillance were selected for this study. Information on the surveillance examinations was obtained from medical reports. The histology of all adenomas was confirmed. Immunohistochemistry was performed in a subgroup of adenomas. RESULTS: We identified 249 carriers and 247 controls. The proportion of subjects free of an adenoma at the age of 60 years was 29.7% for carriers and 70.8% for controls (P < 0.05). The adenomas in carriers were larger, and a higher proportion had villous components and/or high-grade dysplasia (P < 0.05, all analyses). The adenomas and carcinomas of the carriers were located predominantly in the proximal colon. Most adenomas showed absent staining of the MMR proteins. CONCLUSIONS: This study indicates that the MMR defect is involved in the early stages of development of adenomas. We recommend immunohistochemical staining of large adenomas with high-grade dysplasia in young patients (younger than 50 years) to identify patients with suspected HNPCC.     

Variables associated with the risk of colorectal adenomas in asymptomatic patients with a family history of colorectal cancer.

The results of screening individuals referred to the Family Cancer Clinic at St Mark's Hospital from 1986 are presented. Colonoscopy was performed in 644 asymptomatic individuals (from 436 families) with a family history of colorectal cancer. Sixty nine (15.8%) of the families fulfilled the Amsterdam criteria for the hereditary non-polyposis colorectal cancer syndromes (HNPCC). Seven cases of colorectal cancer were diagnosed at an average age of 49 years; six at Dukes's stage A and one at stage C, four in subjects from Amsterdam criteria families. One hundred and forty four (22.4%) subjects had one or more adenomas. The prevalence of adenomas in the subjects from Amsterdam criteria families was 34 of 127 (26.8%) compared with 110 of 517 (21.3%) in those from other families; the age and sex adjusted odds ratio (OR) was 1.76 (p = 0.02). Factors influencing the prevalence of adenomas in screened individuals were evaluated. Multivariate analysis showed that independent variables significantly related to the risk of adenomas were: age (p < 0.0001), sex (p = 0.0002), and the number of generations (> or = 2 v 1) of relatives affected by either colorectal cancer or adenomas (p = 0.0006). The latter variable was more highly predictive of the probability of finding an adenoma at colonoscopy than a family history of two generations with cancer only (p = 0.056). The OR of having colorectal adenomas increased with age, by about twofold for each decade, and was twice as high in men than women, and in subjects with two or more generations relative to those with one generation affected by colorectal cancer or adenomas. Six of seven patients with cancer and 46 of 144 (31.9%) with adenomas had lesions proximal to the splenic flexure only. The proportion of individuals with proximal adenomas only was 47.1% in Amsterdam criteria families and 27.3% in the others (p=0.03). These findings support the view that colonoscopy rather than sigmoidoscopy is the method of choice for screening high risk groups.     

Risk factors for colorectal adenomas among immediate family members of patients with colorectal cancer in Taiwan: a case-control study

OBJECTIVES: The incidence of colorectal cancer or adenoma among first-degree relatives of patients with colorectal cancer is significantly high. However, a well defined screening and surveillance consensus has not been developed for these families in Taiwan. We conducted this study to evaluate the colorectal adenoma prevalence pattern in screened immediate family members in Taiwan, and to derive implications for future screening programs. METHODS: A total of 234 immediate family members (aged 51.6 +/- 21.5 yr) of 186 patients with colorectal cancer were offered a colonoscopy. Each relative examined was then paired with two control subjects for age, sex, and symptoms. The prevalence of colorectal adenomas was then compared using multiple logistic regression analysis. RESULTS: The estimated risk of developing adenomas among immediate family members of patients with colorectal cancer was significantly increased (OR = 2.33; 95% CI, 1.43-3.78; p < 0.001). This trend was more striking for men (OR = 2.46; 95% CI, 1.40-4.31; p = 0.001). Immediate family members were at an increased risk for high-risk adenomas (> or = 1.0 cm, with a villous component, and/or with severe dysplasia) (OR = 4.5; 95% CI, 1.91-10.60; p = 0.002), and developed adenomas at an earlier age than did controls. Individuals with index cancer relatives diagnosed at < 50 yr of age or male relatives posed a higher risk of developing colorectal adenomas. CONCLUSIONS: The prevalence of colorectal adenoma in persons with a colorectal cancer family history in Taiwan is similar to that reported in Western countries. This high-risk population should be offered a screening colonoscopy beginning at 40 yr of age.     

Colorectal adenomas: morphologic features and the risk of developing metachronous adenomas and carcinomas in the colorectum

The morphologic features of 307 colorectal adenomas among 159 patients are reviewed. Most adenomas (66.4%) were located in the sigmoid colon and the rectum, and the percentage decreased proximally to the right colon. The 307 adenomas comprised 244 (79.5%) tubular, 41 (13.3%) tubulovillous, and 22 (7.2%) villous adenomas. The epithelial dysplasia was graded as mild in 260 (84.7%) adenomas, moderate in 33 (10.7%), and severe in 14 (4.6%). The percentage of severe dysplasia was greater in villous adenomas than in tubular adenomas (p less than 0.05) and correlated with the increasing size (greater than 5 mm) of the adenomas (p less than 0.01). The risk of metachronous adenomas could be evaluated among 56 patients, 34 men and 22 women with a history of removed adenoma(s). Fourteen of 56 patients (25%) with 6:1 male to female ratio developed 18 new adenomas, after an average of 34.3 months (range, from 12 to 88 months). Eleven of the 14 patients had multiple adenomas at the initial examination. In addition, a carcinoma of the rectum was found in one male patient. Of the 48 patients, 17 men and 31 women, operated on for colorectal cancer 16 patients (34%) with 1.3:1 male to female ratio had 40 new adenomas after an average of 51.8 months (range, 12 to 252 months) after the surgical excision of their carcinomas. One patient had a recurrent carcinoma at the site of the anastomosis 22 months after anterior resection of his carcinoma. Our data suggest that a history of colorectal carcinoma, multiple adenomas, and male sex predict a higher risk of having future colorectal tumours.     

Type 2 diabetes mellitus: the impact on colorectal adenoma risk in women

OBJECTIVES: Increased risk for colorectal cancer (CRC) has been associated with type 2 diabetes. Despite several studies linking insulin resistance to increased CRC risk, there are limited data on colorectal adenoma risk in diabetic women. We hypothesized that diabetic women would have increased rates of colorectal adenomas relative to a group of nondiabetic women. METHODS: Colorectal adenoma rates were determined in 100 estrogen-negative women with type 2 diabetes mellitus and compared with 500 nondiabetic, estrogen-negative controls. Adenomas were defined as any adenoma or advanced adenoma (villous or tubulovillous features, size >1 cm or high-grade dysplasia). A multivariate model including age, race, diabetes, hypertension, hypercholesterolemia, body mass index, and nonsteroidal anti-inflammatory drug status was used to determine the independent effects of diabetes on colorectal adenoma incidence. RESULTS: Diabetics as compared with nondiabetics had greater rates of any adenoma (37%vs 24%, p= 0.009) and advanced adenomas (14%vs 6%, p= 0.009). Two hundred forty-five obese subjects compared with 355 nonobese subjects had a higher rate of any adenoma (32%vs 22%, p= 0.001). Obese diabetics compared with nonobese, nondiabetics had greater rates of any adenoma (42%vs 23%, p< or = 0.001) and advanced adenomas (19%vs 7%, p< or = 0.001). Multivariate analysis showed that adenomas and advanced adenomas were independently predicted by diabetes (p < 0.05) and adenomas by age. DISCUSSION: Women with type 2 diabetes mellitus had higher rates of colorectal adenomas as compared with lean and nondiabetic women. This finding adds to the evidence that type 2 diabetes is an important factor in the progression of the adenoma-carcinoma sequence.     

Detection of colorectal adenomas by routine chromoendoscopy with indigocarmine

OBJECTIVES: Nonpolypoid adenomas, which can be important precursors of colorectal cancers, are difficult to find during routine colonoscopy. The aim of this study was to evaluate the usefulness of routine chromoendoscopy in Korea, where the incidence of colorectal cancer is low compared with western countries. METHODS: Colonoscopy with chromoendoscopy was performed in 74 consecutive patients (48 men, 26 women; mean age 53.0 yr). After a careful examination of the whole colon, a defined segment of the sigmoid colon and rectum (0-30 cm from the anal verge) was stained with 20 ml of 0.2% indigocarmine solution with a spraying catheter. Nonpolypoid lesions were classified as flat or depressed types. Biopsies were taken from all lesions detected before or after staining with indigocarmine. RESULTS: Indications for colonoscopy included routine check-up (21 patients), diarrhea or loose stool (14 patients), abdominal pain (12 patients), constipation (7 patients), bleeding (6 patients), and others (14 patients). Before staining, 58 lesions were found in 30 patients (43.2%). Histology showed tubular adenoma in 41 lesions, hyperplastic or inflammatory changes in 14 lesions, adenocarcinoma in 2 lesions, and villous adenoma in 1 lesion. After indigocarmine staining for normal-looking distal 30 cm colorectal mucosa, 176 lesions were found in 46 patients (62.2%). Histologically, 158 lesions were hyperplastic or inflammatory in nature, and 17 lesions (from 11 patients) were tubular adenomas. There was one serrated adenoma. Eighteen adenomas seen only after spraying indigocarmine were 2.6 +/- 0.6 mm in diameter, and all of them were classified as flat adenomas. There was no depressed-type adenoma. No adenoma with high grade dysplasia, villous histology, or cancer was found after staining. Presence of macroscopic adenomatous lesions or carcinoma before staining could not predict the existence of adenoma after staining. CONCLUSIONS: In a large proportion of patients, flat or depressed adenomas could be found after spraying indigocarmine for normal-looking colorectal mucosa in Korea. The clinical significance of these diminutive adenomas that can be found only after spraying contrast agent needs to be further investigated.     

Flexible sigmoidoscopy or colonoscopy as a screening modality for colorectal adenomas in older age groups? Findings in a cohort of the normal population aged 63-72 years

BACKGROUND: Most cases of colorectal cancer originate from adenomas. Removing adenomas has been shown to reduce the incidence of colorectal cancer. The design of cost effective endoscopic screening programmes requires a knowledge of the distribution of adenomas in different age groups. AIM: To investigate the distribution of colorectal adenomas in older age groups in the normal population. METHOD: A total of 356 men and women selected randomly from the population register were offered a colonoscopic screening examination to detect and remove polyps. RESULTS: In all, 241(68%) subjects, mean age 67.4 years (range 62-73), attended. The caecum was intubated in 193 (80%), and in this group 32 (38%) women and 51 (47%) men had adenomas. One hundred and ten (54%) of the adenomas and 11 (39%) of the "high risk adenomas" (adenomas larger than 10 mm in diameter, adenomas containing villous components, and adenomas with severe dysplasia) were found proximal to the sigmoid colon. In 36 (43%) of the subjects with adenomas, the adenomas were only found proximal to the sigmoid colon. Twenty two (11%) subjects had more than two adenomas. Of 203 adenomas discovered, 189 (93%) were less than 10 mm in diameter. CONCLUSION: More than half of the adenomas were localised proximal to the sigmoid colon, and, in nearly half of the adenoma bearing subjects examined, the adenoma was proximal to the descending colon. This indicates that a sigmoidoscopic screening examination in this age group would miss a substantial number of adenomas, but this may be acceptable as the vast majority of proximal adenomas do not progress to clinical cancer within the life expectancy of this age group.     

The National Polyp Study. Patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas

The National Polyp Study (NPS), a randomized clinical trial to evaluate effective surveillance of patients discovered to have one or more colorectal adenomas, was the framework for this statistical analysis which used a multiple logistic model to assess the independent risk factors of patient and polyp characteristics associated with high-grade dysplasia in adenomas. The database included 3371 adenomas from 1867 patients. Adenoma size and the extent of the villous component were found to be the major independent polyp risk factors associated with high-grade dysplasia (p less than 0.0001). The adjusted odds ratios were 3.3 for medium-sized adenomas and 7.7 for large adenomas relative to small adenomas and 2.7 for villous A adenomas, 3.4 for villous B adenomas, and 8.1 for villous C and D adenomas relative to tubular adenomas. Increased frequency of high-grade dysplasia in adenomas located distal to the splenic flexure was attributable mainly to increased size and villous component rather than to location per se. The adjusted odds ratio was 1.4 (p less than 0.11) for left-sided location. Multiplicity of adenomas affected the risk for high-grade dysplasia in patients but was dependent on adenoma size and villous component and was not an independent factor. The adjusted odds ratio was 1.3 (p less than 0.17) for multiplicity. Increasing age was associated with risk for high-grade dysplasia in patients, and this effect was independent of the effect of adenoma size and histological type. The adjusted odds ratio was 1.8 (p less than 0.0016) for age greater than or equal to 60 yr. Gender was not associated with high-grade dysplasia. The adjusted odds ratio was 1.0 (p less than 0.95) for men. The size of the patient series, the prospective nature of the data collection, the completeness of information on all patients, the requirements of complete examination of the entire colon and pathological examination of all lesions encountered, and the exclusion of patients with previously diagnosed adenomas are, collectively, features unique to this study. The detailed model provided by the analysis integrates multiple patient and adenoma factors associated with high-grade dysplasia in colorectal adenomas.     

Excessive alcohol consumption favours high risk polyp or colorectal cancer occurrence among patients with adenomas: a case control study.

BACKGROUND AND AIMS: Excessive alcohol consumption is a risk factor for developing colorectal adenomas. This study aimed to investigate the influence of excessive alcohol consumption on the occurrence of high risk polyps (adenoma > or = 10 mm, villous component, high grade dysplasia) or colorectal cancer among patients with at least one colonic adenoma. PATIENTS AND METHODS: Three groups of patients with at least one colorectal adenoma were included in a case control study: 401 heavy drinkers (group HD, mean daily alcohol intake 117 (SD 4) g/day for a mean duration of 22 (SD 0.6) years), aged 57 (0.5) years (78% men); 152 patients suffering from irritable bowel syndrome (IBS), aged 61 (0.9) years (57% male); and 108 patients with a family history (FH) of colorectal adenoma or cancer, aged 55 (1) years (64% male). Exclusion criteria were: anaemia, haematochezia, personal history of colorectal adenoma or cancer, and for groups HD and IBS a family history of colorectal adenoma and/or cancer. Relative risks were estimated by the odds ratio (OR) using a logistic regression model and were expressed with 95% confidence interval (CI). RESULTS: After age and sex adjustment, the likelihood of having an adenoma > or = 10 mm was higher in group HD than in the IBS group (OR 1.8, 95% CI (1.2-2.7)) and the likelihood of having high risk adenomas or cancer was higher in group HD compared with the IBS group (OR 1.6, 95% CI (1.2-2.1)) and the FH group although this was not significant (OR 1.6, 95% CI (0.97-2.6) (p=0.081); 90% CI (1.03-2.4)). After age and sex adjustment, the likelihood of having an adenoma with high grade dysplasia or cancer was higher in group HD than in the IBS group (OR 1.7, 95% CI (1.02-2.8)) or group FH, although this was not significant (OR 3.7, 95% CI (0.98-15) (p=0.076); 90% CI (1.10-12.47)). CONCLUSION: In patients with at least one colorectal adenoma, excessive alcohol consumption increases the likelihood of developing high risk adenomas or colorectal cancer.     

No Major Difference in K-ras and p53 Abnormalities in Sporadic and Hereditary Nonpolyposis Colorectal Adenomas

K-ras and p53 gene mutations are known to occur in high frequencies in sporadic colorectal cancers, but findings are inconsistent in hereditary nonpolyposis colorectal cancer (HNPCC). We compared K-ras codon 12 and 13 gene mutations and p53 protein overexpression in 48 HNPCC (positive for Amsterdam criteria) and 59 sporadic colorectal adenomas, to examine whether they may represent similar or different molecular pathways to cancer. In sporadic adenomas K-ras mutations were detected in 32% and p53 overexpression in 31% of the cases. Similarly, K-ras mutations and p53 overexpression were both found in 25% of HNPCC adenomas. The frequencies of these abnormalities were not significantly different between HNPCC and sporadic adenomas. When taking differences in adenoma size into account, the frequencies were even more similar. In conclusion, these results suggest a similar molecular pathway to adenomas in HNPCC and sporadic carcinogenesis, with respect to involvement of K-ras and p53.     

Genetic epidemiology of mutated K-ras proto-oncogene, altered suppressor genes, and microsatellite instability in colorectal adenomas

BACKGROUND: The genetic epidemiology of colorectal adenomas has not been studied prospectively in colonoscopy patients without cancer. AIMS: To study genetic alterations in colorectal adenomas and correlate these with patient demographics and adenoma characteristics. METHODS: Mutations and allelic deletions in 201 adenomas from 60 patients were compared with demographic features, adenoma characteristics, and family history. RESULTS: The most common alteration was K-ras proto-oncogene mutation, present in 35% of adenomas and 65% of patients. Patients 65 years of age and older had a decreased probability of K-ras mutations (26% versus 45%). Overexpression of p53 gene product was present in only 6% of adenomas but was more frequent in villous or tubulovillous adenomas (19% versus 3%). Allelic loss of chromosome 18q was present in only 2% of adenomas and was significantly less frequent than p53 overexpression. DNA replication errors (RER) were present in 7% of adenomas and 15% of patients, including multiple adenomas in four patients (two with hereditary non-polyposis colorectal cancer syndrome). Only 36% of RER positive adenomas had alteration of BAT-26 alleles, none had alteration of BAT-25, and only one (8%) had mutation in the transforming growth factor beta type II receptor gene. RER positive adenomas were more likely to have a K-ras mutation. In patients with multiple adenomas, there was concordance of p53 overexpression and RER but not of K-ras mutations. CONCLUSIONS: Genetic progression in colorectal adenomas is heterogeneous, involving factors related to patient age and the presence of RER for the occurrence of ras mutations, but different intraindividual characteristics for the occurrence of p53 alterations and RER.     

Proximal adenomas in hereditary non-polyposis colorectal cancer are prone to rapid malignant transformation

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is thought to arise from adenomas. HNPCC mostly occurs in the proximal colon. We investigated whether this proximal preponderance is due to a proximal preponderance of adenomas or (also) differences in transformation rates from adenomas to cancer between the distal and proximal colon. METHODS: A total of 100 HNPCC adenomas were evaluated and compared with 152 sporadic adenomas for location, size, and dysplasia. Twenty five adenomas from patients with a known mismatch repair (MMR) gene mutation were stained for expression of MLH1 and MSH2. RESULTS: HNPCC adenomas were more often located proximally (50% v 26%; p=0.018) and were smaller in comparison with sporadic adenomas. They were similarly dysplastic. However, all proximal HNPCC adenomas > or =5 mm were highly dysplastic compared with 17% of the larger proximal sporadic polyps (p<0.001). They were also more often highly dysplastic than larger distal HNPCC adenomas (p<0.001). Small HNPCC adenomas were, except for their location, not different from sporadic adenomas. Fifteen of the 25 "known mutation" adenomas showed loss of expression of either MLH1 or MSH2. The 10 adenomas with expression were all small with low grade dysplasia. CONCLUSION: HNPCC adenomas are located mainly in the proximal colon. The progression to high grade dysplasia is more common in proximal than distal HNPCC adenomas, indicating a faster transformation rate from early adenoma to cancer in the proximal colon. MMR gene malfunction probably does not initiate adenoma development but is present at a very early stage of tumorigenesis and heralds the development of high grade dysplasia.     

Adenoma prevalence and cancer risk in familial non-polyposis colorectal cancer.

BACKGROUND AND AIMS: Polypectomy in the colon has been shown to prevent colorectal cancer in both the general population and in familial colorectal cancer. Individuals with a family history of colorectal cancer have an increased risk of the disease. Over a period of 10 years, 304 subjects at risk were included in ongoing surveillance with regular colonoscopies. To compile the medical findings and experience generated during this period, a retrospective cross sectional study was performed. SUBJECTS: Subjects were classified into three family groups: families with hereditary non-polyposis colorectal cancer (HNPCC); families with hereditary colorectal cancer (HCC, non-Lynch syndrome); and a third group of families with only empirical risk estimates based on a family history of two close relatives (TCR) with colorectal cancer. METHODS: The risk population was studied with regard to age at onset, prevalence, number, cancer risk, size, dysplasia, and distribution of adenomas. A comparison was made within the family groups and with a reference group representing the general population. RESULTS: In total, 195 adenomas and six cancers were detected among 85 individuals. The relative risk of having an adenoma in the whole risk population compared with the general population was 2.6. Subjects from TCR families had most adenomas and HNPCC subjects had the least. A shift from proximal adenomas to distal carcinomas in families with HCC and TCR suggested a higher cancer risk in distal adenomas in these syndromes. HNPCC families showed a younger age at onset and adenomas with a higher degree of dysplasia. In HNPCC, there was a similar localisation of adenomas and carcinomas, suggesting a high risk of cancer in all adenomas. CONCLUSIONS: There was clear overrepresentation of adenomas in all three family types compared with the reference population. In HNPCC, we found earlier onset of adenomas and faster progression to cancer. Families with HCC, and even more so TCR subjects, had a later onset and lower risk of cancer from proximal adenomas. Based on these results, surveillance protocols in Sweden have been revised.     

Patterns of metachronous adenoma after colorectal cancer surgery]

BACKGROUND/AIMS: After colorectal cancer surgery, colonoscopic surveillance should be done for prevention and early detection of secondary cancer. This study aimed to identify the group with high risk of developing colorectal adenoma after curative surgery of colorectal cancer. METHODS: We retrospectively investigated the medical records of the subjects of 130 patients who had been examined using colonoscopy before and after the curative surgery. RESULTS: The average age was 59.4 years. Synchronous adenomas were in 42 patients (32.3%). The occurrence rate was significantly high in men (38.8%) than women (22.0%). After the operation, the mean interval of examining colonoscopy was 11.6 months (3-24 months) and metachronous adenomas were detected in 26 patients (20.0%). The patients who have both metachronous and synchronous adenomas were observed in 13/42 (30.9%) and the patients of metachronous adenomas without synchronous adenomas were observed in 13/88 (14.8%). The occurrence rate of metachronous adenomas with synchronous adenomas was significantly high. The frequency of synchronous adenomas didn't increase with age. However, the frequency of metachronous adenomas increased with age: 0/9 (0%) under 40 years, 7/49 (14.3%) in 41-61 years and 19/72 (26.4%) over 61 years. The occurrence rate was higher in men (26.3%) than women (10.0%). CONCLUSIONS: The occurrence rate of metachronous adenomas after colorectal cancer surgery was higher in the patients with synchronous adenomas, male gender and old aged patients.     

Adenomas in young patients: what is the optimal evaluation?

Colorectal adenomas are a known risk factor for colorectal cancer. The prevalence of colorectal adenomas among individuals under age 40 and the clinical implications of finding a single adenoma in a young individual have not been defined. Until the most recent revision of the Bethesda Guidelines, having one or more adenomas diagnosed at age <40 was an indication for evaluation for hereditary nonpolyposis colorectal cancer (HNPCC). In an effort to explore the association of young-onset adenomas with HNPCC, Velayos et al. tested adenomas from 34 subjects aged 18-39 for pathologic features of HNPCC. Finding that none of the young-onset adenomas demonstrated features of microsatellite instability (MSI) or loss of mismatch repair protein expression by immunohistochemistry (IHC), the authors conclude that the yield of such testing is low, and support the decision to exclude young-onset adenomas from the Revised Bethesda Guidelines for HNPCC. However, this study also revealed that MSI and IHC failed to detect abnormalities in half of the adenomas from control subjects with identified MLH1 and MSH2 mutations. These findings highlight the limitations of current molecular techniques for examining adenomas as an initial screen for HNPCC and the need for further studies evaluating the optimal genetic and clinical evaluation of patients with young-onset adenomas.     

Increased prevalence of colorectal adenomas in women with breast cancer

BACKGROUND: The frequency of colorectal adenomas and carcinomas was investigated in a large cohort of women with breast cancer in comparison with matched controls, since data on the occurrence of second tumors in women with breast cancer is controversial. DESIGN: In a cohort study, 188 consecutive women (median age 57 years) with primary breast cancer and 376 age-matched women who served as controls were examined by total colonoscopy. Breast cancer patients and controls were compared for the frequency of colorectal adenomas and carcinomas. RESULTS: Women with breast cancer showed a higher risk of colorectal adenomas than controls (14.9 vs. 9.3%, p=0.047, OR 1.7, 95% CI 1.0-2.9). This increased prevalence resulted primarily from an increased prevalence in the age group 65-85 (31 vs. 10%, p=0.004, OR 3.8, 95% CI 1.6-9.3). Colorectal carcinomas were found infrequently in both groups (2 in each group). Women with breast cancer receiving anti-estrogen therapy showed a trend towards a lower risk of adenomas compared to women without anti-estrogen therapy (3.7 vs. 17.2%, p=0.053, OR 0.16, 95% CI 0.0-1.1). CONCLUSIONS: Women with breast cancer above the age of 65 years have an increased risk of colorectal adenomas compared to women without breast cancer. Women with a diagnosis of breast cancer should especially be encouraged to participate in colorectal cancer-screening programs which, in most countries, call for screening of all average-risk individuals over the age of 50 years.     

Clinical significance of small colorectal adenoma less than 10 mm: the KASID study

BACKGROUND/AIMS: Polypectomy is the current modality of choice to prevent benign colorectal adenoma from progressing to an invasive cancer. However, in cases of small colorectal adenoma, it remains unclear as to whether polypectomy is actually an effective treatment modality. We evaluated the clinical significance of polypectomy in cases of small colorectal adenomas, measuring less than 10 mm. METHODOLOGY: All colonoscopies were performed at 11 Korean tertiary medical centers, between July 2003 and March 2004. A total of 5996 colorectal adenomas were detected and divided into 5 groups according to their size (Group 1; 1-5 mm, Group 2; 6-7 mm, Group 3; 8-9 mm, Group 4; 10-19 mm, Group 5; more than 20 mm). The term 'advanced adenoma' refers here to tubular adenomas with diameters of at least 10 mm, or to tubulovillous, villous, or high-grade dysplasia, irrespective of size. 'Cancer' here is defined as the invasion of malignant cells beyond the muscularis mucosa. RESULTS: As the sizes of the adenomas increased, the prevalence of advanced adenoma was also observed to increase. In Groups 2 and 3, the prevalence of tubulovillous or villous adenoma were higher than was expected (5.2% and 6.6%, p < 0.001). Interestingly enough, in Group 2, the prevalence of cancer was at least as high as in Group 4 (0.7% vs. 0.5%, p < 0.001). CONCLUSIONS: In cases of small colorectal adenomas, measuring between 6 and 9 mm, the prevalence of cancer was at least as high as that seen in the cases of colorectal adenomas measuring between 10 and 19 mm. Therefore, small colorectal adenomas measuring between 6 and 9 mm should not be ignored, in order to decrease the prevalence of colorectal cancer.     

The effect of attending a flexible sigmoidoscopic screening program on the prevalence of colorectal adenomas at 13-year follow-up

OBJECTIVES: Understanding the epidemiology of colorectal adenomas is a prerequisite for designing follow-up programs after polypectomy. The aim of the study was to investigate the effect of polypectomy on the long-term prevalence of adenomas. METHODS: In 1983, a total of 799 men and women aged 50-59 yr were drawn from the general population register. Of these, 400 comprised a screening group and 399 a matched control group. The screenees were invited to undergo a once-only flexible sigmoidoscopy. Persons with polyps had a baseline colonoscopy with follow-ups in 1985 and 1989. In 1996, both the screenees and the controls were invited to a colonoscopic examination. RESULTS: In 1996, a total of 451 (71%) individuals attended. Adenomas were found in 78 (37%) individuals in the screening group and 103 (43%) in the control group, relative risk (95% confidence interval): 0.9 (0.7-1.1), p = 0.3, and high-risk adenomas (severe dysplasia, adenomas > or = 10 mm, villous components) were found in 16 (8%) and 32 (13%), respectively; relative risk (95% confidence interval): 0.6 (0.3-1.0), p = 0.07. CONCLUSIONS: There was no significant difference in adenoma prevalence between the group after the screening program and the controls after the usual care. There was a trend toward more high-risk adenomas in the control group. This suggests a very limited effect of one-time screening sigmoidoscopy with surveillance colonoscopy on the prevalence of adenomas, but a preventive effect on the development of high-risk adenomas consistent with the reported effect on cancer prevention.     

Cholecystectomy and the Risk of Colorectal Adenomas

Cholecystectomy has been identified as a risk factor for colorectal cancer, yet little attention has been given to the relationship between cholecystectomy and colorectal adenomas. Utilizing data collected in two large cross-sectional studies of colorectal adenoma risk factors, we examined the association between cholecystectomy and colorectal adenomas. In the adjusted logistic regression model, both men and women showed no effect of cholecystectomy on risk of colorectal adenomas (men: OR 0.67 [95% CI 0.30–1.47]; women: OR 1.46 [95% CI 0.92–2.29]). No effect was seen when examining the time since cholecystectomy for men. There was a slight association found for women who had a cholecystectomy less than 10 years prior (OR 2.02 [95% CI 1.06–3.87]) but no association was seen in women with cholecystectomy at least 10 years prior (OR 1.14 [95% CI 0.62–2.09]). Thus, we conclude that, although cholecystectomy is a risk factor for colorectal cancer, cholecystectomy is not a risk factor for colorectal adenomas.     

ß-catenin, Cox-2 and p53 immunostaining in colorectal adenomas to predict recurrence after endoscopic polypectomy

Background

Endoscopic polypectomy significantly reduces the incidence of colorectal cancer, but recurrence rates are high, especially for adenomas with advanced histology. The present guidelines recommend re-colonoscopy 3 to 5 years later. Due to limited resources, more precise predictions of adenoma recurrence are required.

Design

Lesions from 109 patients with colorectal adenomas recruited into a randomized, placebo-controlled chemoprevention trial with mesalazine were included. Formalin-fixed paraffin-embedded tissue sections were stained for ß-catenin, cyclooxygenase-2 (Cox-2), and p53 and scored. Adenoma recurrence rates were recorded after 3 years and associated with clinical and immunohistochemical parameters by contingency table analysis.

Results

After 3 years, adenomas recurred in 51.4 % of patients. Out of 109 adenomas, 95 met at least one criterion of advanced adenoma (size >1 cm, villous histology, high-grade intraepithelial neoplasia). There was no influence of age, sex, size or villous histology on adenoma reappearance, whilst the number of adenomas at baseline was positively associated with recurrence (p?=?0.003). In contrast, ß-catenin nuclear localisation, Cox-2 expression and p53 nuclear expression were significantly associated with adenoma recurrence after 3 years (ß-catenin: p?=?0.002; Cox-2: p?=?0.001; p53: p?=?0.001). Combining these three markers led to a negative predictive value of 88.5 % and a sensitivity of 94.6 %. (OR?=?13.54)

Conclusions

Scoring each single parameter and, more strongly, the combination of all three parameters of the expression of ß-catenin, Cox-2 and p53 in colorectal adenoma tissue may be a useful negative predictor for adenoma recurrence in patients with advanced colorectal adenomas.