Case-control Study Of Colorectal Cancer Research Articles

Factors associated with colorectal cancer screening in a population-based study: the impact of gender, health care source, and time

Introduction. The effectiveness of colorectal cancer screening in reducing incident colorectal cancer and the risk of death has been shown. Despite campaigns to promote the benefits of and use of colorectal cancer screening, most people are not participating in screening. In this paper, we examine factors associated with screening behavior over time, by health care provider, and by gender and report associations between screening and development of colorectal cancer after adjusting for diet and lifestyle factors. Methods. Data from two population-based case-control studies of colorectal cancer were used to examine risk associations with nonparticipation in colorectal cancer screening. Study participants were identified for the first study between 1991 and 1994 ( N = 1,346 cases and 1,544 controls) and for the second between 1997 and 2001 ( N = 952 cases and 1,205 controls) and were asked to complete a detailed in-person interviewer-administered diet and lifestyle questionnaire. The control population is used to examine changes in screening behavior and associations with screening over time. Results. Significantly, fewer people reported fecal occult blood test (FOBT) in 1997–2001 than in 1991–1994 (62.5% in 1991–1994 vs. 47.2% in 1997–2001); a slight nonsignificant increase in sigmoidoscopy screening was reported for these periods among controls (33.9% vs. 36.6%). In the control population, during these periods, there was a statistically significant increase in the number of people who reported having had a sigmoidoscopy for screening rather than for problems (72.6% in 1997–2001 vs. 63.8% in 1991–1994). There were differences in factors associated with screening behavior by time, by sex, and by health care provider, although having a family history of colorectal cancer, having more education, and being male was associated with more screening in all settings. After adjusting for diet and lifestyle factors, we observed that non-sigmoidoscopy screening significantly influenced risk of incident cancer (rectal OR: 2.9; 95% CI, 2.3–3.7; distal tumor OR: 1.8; 95% CI, 1.4–2.3); proximal tumor: 1.4; 95% CI, 1.1–1.8). Nonuse of FOBT also was associated significantly with tumors in the rectal (OR: 1.6; 95% CI, 1.3–1.9) and distal (OR: 1.4; 95% CI, 1.1–1.8) sites. Summary. These data reinforce the importance of screening to reduce risk of colorectal cancer development. However, flexible sigmoidoscopy screening is increasing only modestly over time, and primarily in settings where a significant investment in screening has been made. FOBT screening, which is effective for rectal cancer prevention, is actually decreasing.

Phenotype of microsatellite unstable colorectal carcinomas: Well-differentiated and focally mucinous tumors and the absence of dirty necrosis correlate with microsatellite instability.

The phenotypic markers of colorectal carcinomas with microsatellite instability have been widely studied and include mucinous or poor differentiation, prominent host response, a circumscribed growth pattern, histologic heterogeneity, and right-sided location. As part of a population-based case-control study of colorectal cancer in northern Israel, we reviewed the pathology and microsatellite status of 528 consecutively diagnosed colorectal cancers. Phenotypic analysis was performed by one pathologist (J.K.G.) and included assessment of grade, mucinous histology (>50%, or focal), histologic heterogeneity, growth pattern, necrosis, and host response. Microsatellite status was determined on microdissected portions of formalin-fixed, paraffin-embedded tissue using a panel of 5 NCI consensus primers. Fifty-two of 528 colorectal carcinomas were microsatellite unstable (9.85%). Multivariate analysis found that >2 tumor infiltrating lymphocytes per high power field (p <0.0001), the lack of dirty necrosis (p = 0.0054), a Crohn's-like host response (p = 0.0064), right-sided location (p = 0.032), well or poor differentiation (p = 0.037), and any mucinous differentiation (p = 0.039) were independent predictors of microsatellite instability. Tumor infiltrating lymphocytes were the single best histologic predictor of microsatellite instability. The absence of dirty necrosis and the presence of well-differentiated tumors and tumors with only focal mucinous differentiation were also important markers for microsatellite instability that have not been emphasized previously. The combination of >2 tumor infiltrating lymphocytes per high power field and/or any mucinous differentiation and/or the absence of dirty necrosis identified all MSI-H tumors in this study.

Oral contraceptives and colorectal cancer

Background. Only limited information and understanding are available on the potential relation between oral contraceptive use and the risk of colorectal cancer. Further data on the issue are therefore useful and may help informed choice of contraception. Methods and results. Data were derived from a case-control study of colorectal cancer conducted between 1992 and 2001 in the Swiss Canton of Vaud, including 131 women with colorectal cancer and 373 controls admitted in the same hospital as the cases with diagnosis of acute, non-neoplastic disease, unrelated to long-term modification of diet. Oral contraceptive use was reported by 11% of cases versus 17% of controls, corresponding to multivariate odds ratio of 0.8 (95% CI: 0.4–1.7). The odds ratio was non-significantly below unity across strata of duration, time since first and last oral contraceptive use. Conclusion. These findings add further evidence on a possible inverse relation between oral contraceptive and colorectal cancer risk.

Analysis of total meat intake and exposure to individual heterocyclic amines in a case-control study of colorectal cancer: contribution of metabolic variation to risk

A case-control study of colorectal cancer, consisting of 157 cases and 380 controls matched by sex, ethnicity, decade of age and county of residence was performed to explore the associations between environmental exposure, metabolic polymorphisms and cancer risk. Participants were required to provide a blood sample, undergo caffeine phenotyping and complete an in-person interview that evaluated meat consumption, cooking methods and degree of doneness. A color atlas of foods cooked to different degrees of doneness was used to estimate food preparation techniques and food models were used to estimate serving portion sizes. Data was analyzed using a reference database of heterocyclic amine (HCA) exposure based on the food preferences chosen from the atlas. Data regarding individual food items cooked to different levels of doneness, as well as summary variables of foods and of food groups cooked to different degrees of doneness were also evaluated in a univariate analysis for association with colorectal cancer case status. Three measures of metabolic variation, hGSTA1 genotype, SULT1A1 genotype and the phenotype for CYP2A6 were also evaluated for possible association with colon cancer. While higher exposure to HCAs was strongly associated with colorectal cancer risk, increased consumption of five red meats cooked well done or very well done produced comparable odds ratios (OR) for colorectal cancer risk (OR=4.36, 95% CI 2.08–9.60) for the highest quartile of exposure. Similarly, individuals in the most rapid CYP2A6 phenotype quartile showed an odds ratio (OR = 4.18, 95% CI 2.03–8.90). The ORs for the low activity hGSTA1 and low activity SULT1A1 alleles were 2.0, 95% CI 1.0–3.7 and 0.6, 95% CI 0.3–1.1, respectively. Individual measures of specific HCAs provided little improvement in risk assessment over the measure of meat consumption, suggesting that exposure to other environmental or dietary carcinogens such as nitrosamines or undefined HCAs may contribute to colorectal cancer risk.

Risk of colorectal cancer from alcohol consumption at lower vitamin intakes. A hospital-based case-control study in Poland.

The purpose of the study was to assess the relation between the simultaneous exposure to alcohol and consumption of micronutrients that have protective properties against colorectal cancer. A hospital-based case-control study of colorectal cancer was carried out between January 1998 and November 1999 at the University Hospital in Krakow, Poland. In total, 180 incident cases of colorectal cancer, confirmed by histopathology, were recruited and an equal number of controls, individually matched by gender and age (+/-5 y), were chosen amongst patients with no history of cancer. A food-frequency questionnaire for 148 food items, combined with the quantity of foods eaten, was used to assess the normal dietary pattern. The data confirmed the reported inverse association between the intake of retinol, thiamine, or antioxidant micronutrients (vitamins C, E) and the occurrence of colorectal cancer. Alcohol intake was found to be an important risk factor for this cancer site, and the risk escalated in parallel with increased intake of retinol, carotene, vitamins C and E, but with high consumption of alcohol ran a noticeably high risk of colorectal cancer (OR= 6.79; 95% CI: 2.08-22.18). The risk was markedly lower, however, among alcohol drinkers who reported a high intake of micronutrients (OR = 1.35; 95% CI: 0.39-4.67). The data suggest that a combination of high consumption of alcohol and low intake of retinol and antioxidant vitamins may considerably increase the risk of colorectal cancer.

NSAIDs and risk of colorectal cancer according to presence or absence of family history of the disease.

We undertook the present analyses to determine whether family history of colorectal cancer in a parent or sibling modifies the inverse association of nonsteroidal anti-inflammatory drug (NSAID) use with colorectal cancer risk. We used data from two case-control studies of colorectal cancer. The hospital-based Case Control Surveillance Study included 1526 patients with primary colorectal cancer, 4192 cancer controls and 6036 noncancer controls. A population-based study conducted in Massachusetts enrolled 1201 incident cases of colorectal cancer and 1201 community controls. Data on NSAID use and risk factors for colorectal cancer were collected by interview. In both studies there was a reduction in the odds ratios among subjects who used NSAIDs regularly continuing into the previous year, regardless of family history. In the Case Control Surveillance data, the odds ratio was 0.4 (95% CI 0.2-0.9) among subjects with a family history and 0.5 (95% CI 0.4-0.7) among subjects without a family history. The comparable odds ratios in the Massachusetts data were 0.5 (95% CI 0.3-0.9) and 0.7 (95% CI 0.6-0.9). These data indicate that regular continuing NSAID use is associated with a reduced risk of colorectal cancer among persons with a family history of the disease, as well as those without such a history.

The association of calcium and vitamin D, and colon and rectal cancer in Wisconsin women.

Calcium and vitamin D have been hypothesized to reduce colorectal cancer risk. Epidemiological evidence, however, is mixed. To explore those relationships, data were collected as part of a population-based, case-control study of colorectal cancer in Wisconsin women (678 controls, 348 colon and 164 rectal cancer cases). A semi-quantitative food frequency questionnaire was used to ascertain food and dietary supplement intake 2 years prior to interview. Logistic regression models were used to calculate odds ratios (OR). Higher levels of calcium intake were associated with reduced colon and rectal cancer risk. The following adjusted OR and 95% confidence intervals (CI) were observed, comparing the fifth quintile (based on control intake) with the first: colon cancer: OR = 0.6, 95% CI: 0.4-1.0, P-trend: 0.03; rectal cancer: OR = 0.6, 95% CI: 0.3-1.1, P-trend: 0.07. Similar relationships were observed for vitamin D intake, although OR were closer to the null value and did not always behave in a step-wise fashion (fifth quintile versus the first--colon cancer: OR = 0.7, 95% CI: 0.4-1.1, P-trend: 0.05; rectal cancer: OR = 0.8, 95% CI: 0.5-1.5, P-trend: 0.42). These data support a protective association of calcium on colon and rectal cancer risk.

The relationship between faecal bile acid profile with or without supplementation with calcium and antioxidants on recurrence and growth of colorectal polyps.

Faecal bile acids (FBA) have been implicated in colon carcinogenesis. The results of case-control studies of colorectal cancer and polyp patients are, however, conflicting. The aim of this study was to examine the influence of faecal bile acids on occurrence, growth and recurrence of colorectal polyps, and to see if a mixture of calcium and antioxidants might possibly act on cancer precursors through the effect on FBA. A total of 116 polyp-bearing patients were recruited from the outpatients department. Polyps < 10 mm in diameter were left in situ and measured by annual colonoscopy for 3 years. The patients received placebo or a mixture of antioxidants and calcium carbonate, 1.6 g calcium ion daily. Faecal samples were collected annually; the first, 1 month after start of intervention, freeze dried and subjected to bile acid profile analysis. Two age and sex matched control groups were recruited (n = 35), one from healthy volunteers (healthy controls) and one from the outpatients referred for colonoscopy, with no polyps (hospital controls). Twelve of 47 patients from the healthy volunteers had polyps (healthy polyp patients). One or more adenomas were found in 93 patients. The faeces of the hospital controls had significantly higher concentrations of total and secondary bile acids than did the healthy controls. There was no difference in FBA profile between the polyp group and the hospital controls, but significantly higher concentration of total and secondary faecal bile acids in the healthy polyp patients compared with the healthy control group (P < 0.05). No increased concentration of FBA were found in the polyp patients with multiple polyps (n = 21) or previous treatment for colorectal cancer (n = 7). No associations between FBA profile and growth or recurrence of colorectal polyps were found. The polyp patients receiving active medication had higher faecal concentrations of total and secondary bile acids in the beginning of the study than at the end, in spite of a good compliance. The present study does not support bile acids as being important markers of initiation or growth of small and medium sized colorectal adenomas. In the present study the calcium and antioxidants did not seem to affect the growth or recurrence of colorectal adenomas by increased TBA excretion in the faeces.

INFLUENCE OF METHODOLOGIC FACTORS IN A POOLED ANALYSIS OF 13 CASE-CONTROL STUDIES OF COLORECTAL CANCER AND DIETARY FIBER

We examined the study design features and data collection methods from 13 case-control studies of colorectal cancer and diet, which had been previously combined and analyzed, to determine whether they influenced the results obtained from a pooled analysis. We assessed the methods used in each study, estimated a quality score, and used random effects models to re-estimate the pooled odds ratio for the association between dietary fiber and colorectal cancer for these data. Key features of the methods used in each study and the quality score were examined in random effects models to determine whether the heterogeneity found between study-specific risk estimates could be explained by these variables. The odds ratio for dietary fiber and colorectal cancer was 0.46 (95% confidence interval = 0.34-0.64) for the 13 case-control studies as estimated with a random effects model. Two factors, whether the diet questionnaire had been validated before use in the case-control study and whether qualitative data on dietary habits and cooking methods had been incorporated into the nutrient estimation, explained some of the heterogeneity found between studies. Risk estimates for dietary fiber and colorectal cancer were closer to the null for the studies that had these two characteristics. Quality score did not explain any between-study heterogeneity. Random effects models, which included fixed effects covariates, explained some between-study heterogeneity in these data and would be useful for future pooled analyses.

A case-control study of colorectal cancer and its relation to diet, cigarettes, and alcohol consumption in Saitama Prefecture, Japan.

A case-control study of colorectal cancer in relation to dietary, smoking, and drinking habits was undertaken in Saitama Prefecture, Japan. The study was based on 181 newly diagnosed cases of adenocarcinoma of the colorectum at a single institution and 653 general population controls. Dietary habits were investigated on the basis of the intake of 12 foods and 12 food groups in a food intake frequency questionnaire, together with individual food preferences. Preference for salty foods was positively related to the risk of both colon and rectal cancer, and the consumption of seaweed was inversely related to these cancers, both with a dose-response relation. Cigarette smoking was inversely related to colon cancer risk, but not to rectal cancer risk. Alcohol intake tended to be associated inversely with colon cancer, but not with rectal cancer. In the multiple logistic regression, preference for salty foods (positively) and the consumption of seaweed (inversely) were independently related to both colon and rectal cancer risks.

Colorectal adenomas and energy intake, body size and physical activity: a case-control study of subjects participating in the Nottingham faecal occult blood screening programme

Most case-control studies of colorectal cancer have shown a positive association with energy intake. In contrast studies which have considered physical activity have found the most active to have a lower risk of colonic cancer and obesity appears to be no more than weakly related to colorectal cancer. We therefore compared energy intake determined by a diet history interview, self-reported height and weight, together with measures of lifetime job activity levels and leisure activity in the year prior to interview in 147 cases with colorectal adenomas and two control groups (a) 153 age-sex matched FOB-negative subjects (b) 176 FOB-positive subjects in whom no adenoma or carcinoma was found. Unconditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals () adjusted for age, sex and social class. No association with weight or body mass index was found. The only association with physical activity found with both control groups was an inverse association with running or cycling for half an hour continuously at least once a week RR 0.46 (0.2-1.3) compared with control group (a), and RR = 0.32 (0.1-0.8) compared with (b), but few subjects engaged in such activity. There was an inverse association with energy intake (trend chi 2 = 5.3, P < 0.025) in the comparison with control group (a) only, a finding which is consistent with those of two previous studies of asymptomatic adenoma.

Attributable risk for diet, alcohol, and family history in the Melbourne Colorectal Cancer Study.

From the data obtained in a large comprehensive population-based case-control study of colorectal cancer (The Melbourne Colorectal Cancer Study), attributable risk was calculated for a family history of colorectal cancer in near relatives for diet (when > or = 5 of the 11 previously determined dietary risk factors were present) and for beer consumption (for rectal cancer only). The attributable risk was 11% in the presence of a family history of colorectal cancer and 46% in the presence of five or more dietary risk factors. The attributable risk for rectal cancer in the presence of beer consumption was 31% in males and 11% in females. These data are relevant in the consideration of primary prevention of colorectal cancer in Australia, but their general application needs to be approached with caution in view of major differences in the genetic background and the dietary practices in various regions of the world and in view of the uncertainty of what is achievable change, especially for dietary practices.

An analytical method for assessing patterns of familial aggregation in case-control studies.

This paper describes an analytical method that is used to assess patterns of disease aggregation within family based on family history information collected in case-control studies. In such a study, cases and controls are thought of as probands whose relatives are identified, and relatives' phenotypes and other covariates such as age, sex, and genealogical relationship with the probands are recorded. By modeling the dependence of relatives' phenotypes on case-control status and other covariates, this method yields adjusted odds ratios that quantify familial aggregation. The estimated standard errors are obtained for statistical inference since the method acknowledges the potential correlations between relatives' phenotypes by using the estimating equations technique. In population-based case-control studies, the estimates and statistical inferences are generalizable to the general population. To illustrate this method, we analyzed a case-control study of colorectal cancer involving 5,190 relatives of 792 cases and 4,478 relatives of 680 population-based controls conducted in Hawaii. Although detailed results will be presented elsewhere, the colorectal cancer was found to aggregate within family with an odds ratio of 2.74 (95% confidence interval (CI): 1.78-4.21). Among parents, the odds ratio for familial aggregation was 2.38 (95% CI: 1.25-4.54). The corresponding value for siblings was 3.09 (95% CI: 1.87-5.11). It was also found that the odds ratio increases from about 2.00 for relatives of the probands who were 50 years or older to 7.66 and 12.84 for relatives of the probands who were between 40 and 50 years and under 40 years, respectively, suggesting that the familial aggregation of colorectal cancer decreases as probands' age increases.

Diet, Physical Activity, and Colorectal Cancer Among Chinese in North America and China

In a population-based case-control study of colorectal cancer among Chinese men and women in western North America and the People's Republic of China, a common protocol was used to assess past life-style characteristics of 905 cases diagnosed during 1981-1986 and 2,488 controls. Risks for cancers of both the colon and rectum increased with increased food energy from fat, protein, carbohydrate, and all energy sources combined, for both sexes and on both continents. Yet, in multivariate analysis, colorectal cancer risk was significantly associated only with saturated fat; no relationships were seen with other dietary sources of energy. Colon cancer risk was elevated among men employed in sedentary occupations. On both continents and in both sexes, risks for cancers of both the colon and rectum increased with increasing time spent sitting. Further, the association between colorectal cancer risk and saturated fat was stronger among the sedentary than among the active. Risk among sedentary Chinese Americans of either sex increased more than fourfold from the lowest to the highest category of saturated fat intake. Among migrants to North America, risk increased with increasing years lived in North America. These observations suggest (a) that colorectal cancer risk increases with duration of exposure to a sedentary life-style and a diet rich in saturated fat; (b) that higher incidence among Chinese-American men relative to women is due to longer duration of these habits among men, who have lived longer in North America; and (c) that higher risk among Chinese Americans of both sexes relative to risk among the general population in China is due to differences in such habits. Attributable risk calculations suggest that, if these associations are causal, saturated fat intakes exceeding 10 g/day, particularly in combination with physical inactivity, could account for 60% of colorectal cancer incidence among Chinese-American men and 40% among Chinese-American women.

Dietary sodium and potassium intake and colorectal cancer risk.

In a large, comprehensive, population-based case-control study of colorectal cancer (The Melbourne Colorectal Cancer Study), a high intake of sodium was shown to be a statistically significant risk factor for rectal cancer in males (RR = 1.72, p = 0.01) and was close to statistical significance in females (RR = 1.58, p = 0.06). This was independent of previously described dietary risk factors and also independent of the previously described beer risk. A high intake of potassium was protective for both males and females, but this effect disappeared after adjustment was made for the previously described dietary risk factors. A high ratio of dietary potassium to sodium was a statistically significant protective factor in females for both colon and rectal cancer, and the significance of this effect was reduced after adjustment was made for the previously described dietary risk factor (RR for colon cancer = 0.70, p = 0.08; RR for rectal cancer = 0.67, p = 0.08). So far, no biological explanations are available for these associations, and while they are of obvious etiologic interest, they should be interpreted with caution.

Epidemiology of fecal mutagenicity.

Fecal mutagenicity presents unique difficulties of measurement (63); nonetheless, population studies of fecal mutagenicity typify the common methodological problems of colorectal cancer epidemiology. For example, correlational studies have linked fecal mutagenicity both to colorectal cancer incidence and to dietary practices postulated to increase the risk of colorectal cancer. The threat of an ecologic fallacy, however, is just as strong for biochemical assays as for other epidemiologic data. Fecal mutagenicity may represent, along with high-fat or low-fiber intake, a mere correlate of some true risk factor still to be elucidated in high-risk populations. Dietary trials, on the other hand, may directly confirm the influence of diet on fecal mutagenicity (or another presumed "intermediate end point") but cannot directly address the relationship of mutagenicity to colorectal cancer risk. Case-control comparisons of fecal mutagenicity might initially seem to promise more compelling evidence regarding colorectal cancer risk, but they are actually unsuitable, since the possibility of disease affecting this "exposure" is so strong. Specifically, fecal mutagenicity might be affected by the clinical tests required to diagnose colorectal cancer; it might also be affected by the malignancy itself, or indirectly by the dietary modifications that can accompany gastrointestinal illness. The resultant biases threaten to confound a case-control comparison as much as recall bias can affect interview data. A proper case-control study of fecal mutagenicity and colorectal cancer must therefore consider the effect of diagnostic workup on each mutagenicity assay, before the test is used to compare case and control specimens. In addition, case subjects should be followed through hospitalization and recovery, in the hope that for some cured patients the measurements after surgery will exclude any effect of disease on exposure. A case-control study incorporating these extra efforts is now underway. It seems reasonable to state that most biochemical assays incorporated into case-control studies of colorectal cancer will require similar modifications. Moreover, even if an effect of disease or of health care on biochemical measurements is excluded, an additional concern regarding the role of fecal mutagenicity or other assays in case-control studies will remain. The use of biochemical tests in a case-control context is analogous to asking questions regarding current smoking or current diet in a case-control interview. The current measurements reflect past values only to the degree that the exposure variable remains stable during the subject's lifetime.(ABSTRACT TRUNCATED AT 400 WORDS)

Age at First Pregnancy and Risk of Colorectal Cancer: A Case-Control Study&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;

Results from a case-control study of colorectal cancer conducted in Toronto and Calgary, Canada, are reported with respect to pregnancy-related variables. A total of 158 female "ever-married" colon cancer cases, 71 rectum cancer cases, 242 neighborhood controls, and 257 hospital controls were interviewed to obtain a complete pregnancy history. The results indicate a strong protective effect of early age at first pregnancy for both colon and rectum cancers, with little or no effect noted for the total number of pregnancies. There is a suggestion that age at first pregnancy may have a greater effect on right colon cancer than on left colon cancer. In addition, there also is a suggestion that non-live-birth outcomes may be a risk factor for both colon and rectum cancer. The similarity of these results to those of other studies on large bowel cancer and on breast cancer support the hypothesis that carcinogenesis in the large bowel may be at least partly mediated by female sex hormones.