Distal Colon Adenoma Research Articles

Genetic polymorphism of cholesterol 7α‐hydroxylase (CYP7A1) and colorectal adenomas: Self Defense Forces Health Study

Bile acids have long been implicated in colorectal carcinogenesis, but epidemiological evidence is limited. Cholesterol 7alpha-hydroxylase (CYP7A1) is the rate-limiting enzyme producing bile acids from cholesterol. A recent case-control study showed a decreased risk of proximal colon cancer associated with the CC genotype of the CYP7A1 A-203C polymorphism. The present study examined the relationship between the CYP7A1 A-203C polymorphism and colorectal adenoma, which is a well-established precursor lesion of colorectal cancer. The study subjects comprised 446 cases of colorectal adenomas and 914 controls of normal total colonoscopy among men receiving a preretirement health examination at two hospitals of the Self Defense Forces (SDF). The CYP7A1 genotype was determined by the polymerase chain reaction-restriction fragment length polymorphism method. Statistical adjustment was made for age, hospital, rank in the SDF, smoking, alcohol use, body mass index, physical activity and parental history of colorectal cancer. The CYP7A1 polymorphism was not measurably related to the overall risk of colorectal adenomas. However, the CC genotype was associated with a decreased risk of proximal colon adenomas, but not of distal colon and rectal adenomas. Adjusted odds ratios of proximal colon adenomas (95% confidence intervals) for the AC and CC genotype versus AA genotype were 0.82 (0.54-1.24) and 0.56 (0.34-0.95), respectively. The findings add to evidence for the role of bile acids in colorectal carcinogenesis. The CC genotype of the CYP7A1 A-203C polymorphism probably renders lower activity of the enzyme synthesizing bile acids.

Dietary Marinen-3 Fatty Acids in Relation to Risk of Distal Colorectal Adenoma in Women

Epidemiologic studies of dietary marine n-3 fatty acids and risk of colorectal cancer have been inconsistent, and their relation to risk of colorectal adenoma has not been evaluated in detail. We examined dietary marine n-3 fatty acids and the ratio of marine n-3 to total n-6 fatty acids (n-3/n-6 ratio) in relation to risk of adenoma of the distal colon or rectum among 34,451 U.S. women who were initially free of colorectal cancer or polyps, who completed a semiquantitative food frequency questionnaire in 1980, and who underwent endoscopy from 1980 to 1998. We documented 1,719 distal colorectal adenoma cases (705 large adenomas, 897 small adenomas, 1,280 distal colon adenomas, and 505 rectal adenomas) during 18 years of follow-up. Neither dietary marine n-3 fatty acids nor n-3/n-6 ratio were associated with risk of total distal colorectal adenoma after adjustment for age and established risk factors [multivariable relative risk (RR) for extreme quintiles of dietary marine n-3 fatty acids = 1.04; 95% confidence interval (95% CI), 0.84-1.27, P(trend) = 0.66; RR for extreme quintiles of n-3/n-6 ratio = 1.02; 95% CI, 0.83-1.25; P(trend) = 0.86]. Similarly, no significant associations were observed separately for distal colon or rectal adenoma. However, higher intake of dietary marine n-3 fatty acids was nonsignificantly but suggestively inversely associated with large adenoma (RR, 0.74; 95% CI, 0.54-1.01; P(trend) = 0.16) but directly associated with small adenoma (RR, 1.36; 95% CI, 1.02-1.81; P(trend) = 0.09). Our findings do not support the hypothesis that a higher intake of marine n-3 fatty acids or a higher n-3/n-6 ratio reduces the risk of distal colorectal adenoma but are suggestive that higher intake may reduce the progression of small adenomas to large adenomas.

Dietary patterns and risk of colon cancer and adenoma in a cohort of men (United States)

Examining the effects of dietary patterns on cancer risk may provide insights beyond the assessment of individual foods or nutrients. In the health professionals follow-up cohort, associations between the 'prudent' and the 'western' dietary pattern and risk of colon cancer and adenomas were examined in 561 colon cancer cases and 1207 distal colon adenoma cases. Higher prudent pattern scores were only weakly and non-significantly associated with decreased risk of colon cancer or distal colon adenoma (highest versus lowest quintile: colon cancer: multivariate adjusted relative risk (RR) = 0.84 (95% confidence interval (CI) = 0.64-1.10); p(trend) = 0.37; distal adenoma: multivariate odds ratio (OR) = 0.88 (95% CI = 0.73-1.08); p(trend) = 0.12). Our findings suggest a moderately increased risk of colon cancer and distal adenoma with higher western pattern scores (colon cancer: RR = 1.27 (95% CI = 0.96-1.69), p(trend) = 0.05; distal adenoma: OR = 1.28 (95% CI = 1.05-1.56), p(trend) = 0.01). Adding body mass index, which is positively related to western pattern and thus may be considered an intermediate endpoint between western pattern and colon cancer, attenuated associations somewhat but not substantially. Our data do not provide evidence for an appreciable inverse association between higher prudent pattern scores and risk of colon cancer or distal colon adenomas, but do support a moderate positive association between higher western pattern scores and risk of colon cancer or distal colon adenomas.

Glycemic Index, Glycemic Load, and Carbohydrate Intake in Relation to Risk of Distal Colorectal Adenoma in Women

Abstract Case-control studies and a cohort study have shown inconsistent associations between a high glycemic index or a high glycemic load and risk of colorectal cancer. These dietary variables have not been examined in relation to risk of colorectal adenoma. We thus examined the associations between dietary glycemic index, glycemic load, and carbohydrate intake with risk of adenoma of the distal colon or rectum among 34,428 US women who were initially free of cancer or polyps, who completed a semi-quantitative food-frequency questionnaire in 1980, and who underwent endoscopy from 1980 through 1998. 1,715 adenoma cases (704 large adenomas, 894 small adenomas, 1,277 distal colon adenomas, and 504 rectal adenomas) were documented during 18 years of follow-up. Dietary glycemic index, glycemic load, and carbohydrate intake were not related to risk of total colorectal adenoma after adjustment for age and established risk factors [relative risk (RR) for extreme quintiles of glycemic index = 1.11, 95% confidence interval (CI) 0.94-1.32, P for trend = 0.66; RR for glycemic load = 0.92, 95% CI 0.76-1.11, P for trend = 0.63; RR for carbohydrate intake = 0.90, 95% CI 0.73-1.11, P for trend = 0.64]. In addition, no significant associations were found for large or small adenoma, distal colon or rectal adenoma, or across strata of body mass index. Our findings do not support the hypothesis that a high glycemic index diet, a high glycemic load diet, or high carbohydrate intake overall are associated with risk of colorectal adenoma.

Aberrant CpG island hypermethylation of multiple genes in colorectal neoplasia

CpG island hypermethylation is a potential means of inactivating tumor suppressor genes, and many genes have been demonstrated to be hypermethylated and silenced in colorectal cancer. However, limited data is available upon the concurrent methylation of multiple genes in colorectal cancer and in its precursor lesion. To address changes in the methylation profiles of multiple genes during colorectal carcinogenesis, we investigated the methylation of 12 genes (APC, COX-2, DAP-kinase, E-cadherin, GSTP1, hMLH1, MGMT, p14, p16, RASSF1A, THBS1, and TIMP3) in normal colon (n=24), colon adenoma (n=95), and colorectal cancer (n=149), using methylation-specific PCR. The average number of these genes methylated per sample was 0.12, 1.8, and 3.0 in normal colon mucosa, adenoma, and carcinoma, respectively, showing a stepwise increase (P<0.001). All the genes were methylated in colorectal cancer at frequencies varying from 51 to 9.4% and colon adenoma displayed methylation for the 11 genes, except for GSTP1, at frequencies varying from 40 to 1.1%. In contrast, normal colon mucosa demonstrated methylation for APC only, at a frequency of 12.5%. The total number of methylated genes per tumor showed a continuous, nonbimodal distribution in colon adenoma or cancer. CpG island hypermethylation exhibited a proclivity toward proximal colon cancer or adenoma, and the average number of genes methylated was higher in proximal colon cancer or adenoma than in distal colon cancer or adenoma, respectively (3.5 vs 2.6, P=0.018 for cancer, and 2.5 vs 1.4, P=0.003 for adenoma).In conclusion, concurrent CpG island methylation is an early and frequent event during colorectal carcinogenesis. It appears that CpG island methylation plays a more important role in proximal colon cancer development than in distal colon cancer development.

Small early tubular adenomas and mixed colonic polyps found on screening flexible sigmoidoscopy do not predict proximal neoplasia in males

Background & Aims : Distal colonic adenomas found on flexible sigmoidoscopy are associated with proximal neoplasias, thus requiring a complete colonoscopic examination, but data regarding the association of distal mixed polyps with proximal neoplasia are lacking. We conducted this study to elucidate the significance of distal mixed colonic polyps in predicting proximal neoplasia. Methods : We retrospectively analyzed data from patients who underwent a flexible sigmoidoscopic examination for colorectal cancer screening and a follow-up colonoscopic examination because of distal colonic polyps. Distal index polyps were classified by a pathologist as early tubular adenoma (ETA), serrated, or true mixed categories. Index polyps also were immunostained with a monoclonal antibody, Adnab-9, a marker for the colorectal adenoma carcinoma sequence. Results : In 636 patients with distal index polyps, 6% were malignant, 55% were adenomas, 13% were ETAs, 6% were serrated, 4% were true mixed, and 17% were hyperplastic. Compared with distal hyperplastic index polyps, distal malignant polyps ( P = 0.0006) and adenomas ( P = 0.001) were associated with a significantly increased number of synchronous proximal neoplasia, but the small distal mixed, serrated, or ETA did not predict the increased incidence of proximal neoplasia. Large distal polyps of each category were significantly associated with an increased number of synchronous proximal neoplasias. In support of these findings, immunostaining of distal polyps with Adnab-9 showed predictability for proximal neoplasia only in the adenoma category ( P < 0.05). Conclusions : Small ETAs, serrated, or mixed polyps found on flexible sigmoidoscopic examination do not increase the probability of synchronous proximal neoplasia.

Relation of cigarette smoking and alcohol use to colorectal adenomas by subsite: the self-defense forces health study.

While smoking has consistently been shown to be related to increased risk of colorectal adenomas, few studies have addressed the association between smoking and site-specific colorectal adenomas. The reported association between alcohol use and colorectal adenomas has been inconsistent. We evaluated risks of adenomas at the proximal colon, distal colon, and rectum in relation to cigarette smoking and alcohol use, and their interaction. Subjects were 754 cases with histologically proven colorectal adenomas and 1547 controls with normal colonoscopy among male officials of the Self-Defense Forces (SDF) undergoing total colonoscopy at two SDF hospitals. Statistical adjustment was made for hospital, rank, body mass index, physical activity, and either smoking or alcohol drinking. Cigarette smoking was significantly associated with an increased risk of adenomas, regardless of the location of the adenomas, but the increased risk associated with smoking was more pronounced for rectal adenomas. Alcohol use was associated with moderately increased risks of distal colon and rectal adenomas, but not of proximal colon adenomas. Cigarette smoking, but not alcohol drinking, was associated with greater increases in the risk of large adenomas and of multiple adenomas across the colorectum. There was no measurable interaction of cigarette smoking and alcohol drinking on colorectal adenomas. The findings corroborate an increased risk of colorectal adenomas associated with smoking and a weak association between alcohol use and colorectal adenomas. Further studies are needed to confirm whether smoking is more strongly related to rectal adenomas, large adenomas, or multiple adenomas.

Dietary fibre and colorectal adenoma in a colorectal cancer early detection programme

Peters, Ulrike; Sinha, Rashmi; Chatterjee, Nilanjan; Subar, Amy F; Ziegler, Regina G; Kulldorff, Martin; Bresalier, Robert; Weissfeld, Joel L; Flood, Andrew; Schatzkin, Arthur; Hayes, Richard B for the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial Project Team

Dietary fibre and colorectal adenoma in a colorectal cancer early detection programme

Although dietary fibre has been reported to have no association with colorectal adenoma and cancer, in some studies this topic remains controversial. We used a 137-item food frequency questionnaire to assess the relation of fibre intake and frequency of colorectal adenoma. The study was done within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomised controlled trial designed to investigate methods for early detection of cancer. In our analysis, we compared fibre intake of 33971 participants who were sigmoidoscopy-negative for polyps, with 3591 cases with at least one histologically verified adenoma in the distal large bowel (ie, descending colon, sigmoid colon, or rectum). Odds ratios were estimated by logistic regression analysis. High intakes of dietary fibre were associated with a lower risk of colorectal adenoma, after adjustment for potential dietary and non-dietary risk factors. Participants in the highest quintile of dietary fibre intake had a 27% (95% CI 14-38, p(trend)=0.002) lower risk of adenoma than those in the lowest quintile. The inverse association was strongest for fibre from grains and cereals and from fruits. Risks were similar for advanced and non-advanced adenoma. Risk of rectal adenoma was not significantly associated with fibre intake. Dietary fibre, particularly from grains, cereals, and fruits, was associated with decreased risk of distal colon adenoma.

Predicting advanced proximal colonic neoplasia with screening sigmoidoscopy.

Indications are not well defined for follow-up colonoscopy for all patients with distal colonic tubular adenomas (TAs) found at screening sigmoidoscopy. To determine whether distal adenoma size, number, and villous histology, along with family history and age, are predictors of advanced proximal colonic neoplasia. Cross-sectional analysis conducted between January 1, 1994, and December 31, 1995. Large group-model health maintenance organization in northern California. A total of 2972 asymptomatic subjects aged 50 years or older undergoing colonoscopy as follow-up to a screening sigmoidoscopy. Based on sigmoidoscopy, colonoscopy, and pathology reports, occurrence of advanced proximal neoplasia, defined as adenocarcinoma or TAs 1 cm or larger or with villous features or severe dysplasia located beyond sigmoidoscopic view. The prevalence of advanced proximal neoplasia was similar among patients with no TAs at sigmoidoscopy, those with TAs less than 1 cm in diameter, and those with TAs 1 cm in diameter or larger (prevalence, 5.3%, 5.5%, and 5.6%, respectively). Of patients with a distal tubulovillous or villous adenoma, 12.1% had advanced proximal neoplasia. In multivariate analyses, having a distal tubulovillous adenoma or villous adenoma was the strongest predictor of advanced proximal neoplasia (odds ratio, 2.30; 95% confidence interval, 1.69-3.14). Age of 65 years or older, having more than 1 adenoma, and a positive family history of colorectal cancer were also significant predictors. Distal adenoma size was not a significant predictor in any multivariate analyses. Advanced proximal neoplasia is not uncommon in subjects with or without distal TAs, but subjects with advanced distal histology and those older than 65 years are at increased risk. Age-specific screening using sigmoidoscopy starting at ages 50 to 55 years and colonoscopy after age 65 years may be justified.

Parity and other reproductive factors and risk of adenomatous polyps of the distal colorectum (United States).

Evidence for an effect of reproductive factors on colorectal carcinogenesis is inconsistent and little is known about their role in development of precursor adenomatous polyps. We evaluated the relation between reproductive factors and distal colorectal adenomas (n = 982) during 14 years of follow up of 26,983 participants in the Nurses' Health Study (United States). The women were free of diagnosed cancer or polyps in 1980, underwent endoscopy 1980-94, and had reported on their parity, oral contraceptive (OC) use, and ages at menarche, first term-pregnancy, and menopause. We calculated relative risks (RR) and 95 percent confidence intervals (CI) using multiple logistic regression. Women with higher parity had an increased risk of adenomas of the distal colorectum (P trend = 0.004; 6+ cf 0 parity: RR = 1.3, CI = 0.9-1.8) or distal colon (P trend = 0.002, RR = 1.7, CI = 1.2-2.6). This association was significantly stronger among women with a family history of colorectal cancer (P interaction = 0.03); comparing 6+ term-pregnancies with nulliparity, among those with a family history, the RR for distal colon adenoma was 3.2 (CI = 1.4-7.2), while among those without a family history, the RR was 1.3 (CI = 0.8-2.2). We observed no association for distal colorectal adenoma and age at menarche, age at first term-pregnancy, ever use of OCs, or menopausal status. Further work is needed to clarify the relation of parity with colon adenoma risk.

Case-control Study of Bowel Habits and Colorectal Adenoma andCancer

The association between bowel habits and colorectal neoplasms was studied in a case-control study involving 520 cases with colorectal adenoma, 217 cases with colorectal cancer, 638 hospital controls without no endoscopical findings in the large intestine and 577 population controls. Compared with population controls, the relative risk (RR) for soft stools were in-creased for every site of colorectal adenoma and cancer and that for hard stools was increased for colon adenoma and cancer. However, these associations were not observed with hospital controls. The RRs for rectal and distal colon adenomas and rectal cancer, compared with either control group, progressively increased with increasing the number of bowel movements.The RR for two or more bowel movements per day, adjusted for other confounding factors, was 2.11 (95% confidence interval (CI): 1.24-3.60) for distal colon adenoma, 3.52 (95% CI : 1.56-7.93) for rectal adenoma and 7.72 (95% Cl : 3.18-18.76) for rectal cancer, compared with hospital controls. All of the associations are not likely to be explained by effects of disease. These results suggest that bowel habits indicating diarrhea and underlying inflammation may increase the risk of neoplasms in the distal colon and rectum. J Epidemiol, 1993; 3 : 1-5.

Distal colonic hyperplastic polyps do not predict proximal adenomas in asymptomatic average-risk subjects

The significance of distal colonic hyperplastic polyps was investigated in 482 asymptomatic average-risk subjects, aged 50–75 years, in whom fecal occult blood test results were negative and who underwent screening colonoscopy. The incidence of adenomas in the colon proximal to the sigmoid-descending colon junction in subjects with hyperplastic polyps distal to that point was 18% and was similar to the incidence of proximal colonic adenomas in subjects with no distal colonic polyps (15%). The incidence of proximal colonic adenomas in subjects with distal colonic adenomas was 38% and was significantly greater than the incidence found in individuals with no distal colonic polyps or only hyperplastic polyps. Our data do not support distal colonic hyperplastic polyps as markers for proximal colonic adenomas in asymptomatic average-risk subjects.

Distal and Proximal Colon Adenomas

To the Editors: In the report of their prospective study of whether distal colonic hyperplastic polyps are a marker for proximal adenomatous polyps in symptomatic patients, Provenzale and colleague...

A Comparative Case‐Control Study of Colorectal Cancer and Adenoma

We conducted a comparative case‐control study of colorectal cancer and adenoma involving 221 cases with colorectal cancer, 525 cases with colorectal adenoma and 578 neighborhood controls. Daily vegetables intake was associated with lower risks of distal colon adenoma (relative risk (RR)=0.59, 95% confidence interval (CI): 0.39–0.89) and rectal cancer (RR=0.46, 95% CI: 0.25–0.84). Daily beans intake was associated with lower risk of colon adenoma (RR=0.58, 95% CI: 0.37–0.91 for the proximal colon and RR=0.63, 95% CI: 0.45–0.88 for the distal colon) and daily intake of seaweeds was associated with lower risk of rectal cancer (RR=0.42, 95% CI: 0.22–0.82). Daily intake of fish and shellfish also showed an inverse association with the risk of colon adenoma (RR=0.67, 95% CI: 0.45–0.99 for the proximal colon and RR=0.70, 95% CI: 0.52–0.94 for the distal colon). Generally, intakes of animal or vegetable fat‐rich foods, especially meats, were associated with decreases in risks of both adenoma and cancer, though the association of cancer was not statistically significant. Other than dietary factors, daily alcohol drinking was associated with an increased risk of adenoma in the proximal colon (RR=1.95, 95% CI: 1.15–3.29) and ex‐drinkers showed higher risks for colon adenoma and colorectal cancer. Sports or occupational activities and coffee drinking were inversely associated and family history of colorectal cancer was positively associated with the risks of both colorectal adenoma and cancer.