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PubMed2004

Effects of commercial anthocyanin-rich extracts on colonic cancer and nontumorigenic colonic cell growth.

Commercially prepared grape (Vitis vinifera), bilberry (Vaccinium myrtillus L.), and chokeberry (Aronia meloncarpa E.) anthocyanin-rich extracts (AREs) were investigated for their potential chemopreventive activity against colon cancer. The growth of colon-cancer-derived HT-29 and nontumorigenic colonic NCM460 cells exposed to semipurified AREs (10-75 microg of monomeric anthocyanin/mL) was monitored for up to 72 h using a sulforhodamine B assay. All extracts inhibited the growth of HT-29 cells, with chokeberry ARE being the most potent inhibitor. HT-29 cell growth was inhibited approximately 50% after 48 h of exposure to 25 microg/mL chokeberry ARE. Most importantly, the growth of NCM460 cells was not inhibited at lower concentrations of all three AREs, illustrating greater growth inhibition of colon cancer, as compared to nontumorigenic colon cells. Extracts were semipurified and characterized by high-pressure liquid chromatography, spectrophotometry, and colorimetry. Grape anthocyanins were the glucosylated derivatives of five different anthocyanidin molecules, with or without p-coumaric acid acylation. Bilberry contained five different anthocyanidins glycosylated with galactose, glucose, and arabinose. Chokeberry anthocyanins were cyanidin derivatives, monoglycosylated mostly with galactose and arabinose. The varying compositions and degrees of growth inhibition suggest that the anthocyanin chemical structure may play an important role in the growth inhibitory activity of commercially available AREs.

Anthocyanins↗
PubMed1998

Survival of normal colonic epithelial cells from both rats and humans is prolonged by coculture with rat embryo colonic fibroblasts.

Primary cultures of normal colonic epithelial cells from both humans (HCEC) and rats (RCEC) have been established using coculture with colon fibroblasts isolated from rat term embryos. While no other factors we have analyzed had any effect on the survival of epithelial cells, which is normally 3-4 days, coculture with viable fibroblasts extended this period to at least 2 weeks. The effects depended on early passages and low seeding densities of the fibroblasts and on direct cell-cell contact. We have obtained cultures of epithelial cells expressing keratin, laminin, and uvomorulin, displaying a polygonal, epithelial morphology and forming microvilli. DNA synthesis as measured by BrdU uptake into DNA varied widely between colonies of the same culture depending on cell morphology: flat colonies of RCECs contained 5.7% +/- 0.56% BrdU-positive cells, while the proportion in dense three-dimensional colonies reached 50.3% +/- 2.6%. In HCECs the growth fraction was lower, but showed the same distribution between classes of colonies. In the presence of rat embryonic colon fibroblasts, growth factors exerted survival activity on colonic epithelial cells. Consecutive addition of insulin and epidermal growth factor/fibroblast growth factor (EGF/FGF) increased colony number (15.0 +/- 1.0 and 23.0 +/- 2.0 colonies/well respectively; p < or = 0.05 increased above control) and size (1022 +/- 155 and 1207 +/- 158 cells/colony respectively; p < or = 0.05 increased above control) compared to serum-free control medium and basic MEM without growth factors. BrdU labeling index was not increased, however: EGF/FGF actually decreased BrdU labeling from 33.2% +/- 3.9% in controls to 21.3% +/- 3.8% in the EGF/FGF group (p < or = 0.05) owing to the high proportion of flat colonies consisting of resting cells. The newly established culture model can now be used to investigate growth control mechanisms in colonic mucosa and the effects of toxic and/or tumor-promoting substances on these mechanisms.

Animals↗
PubMed2005

Expression of D-type cyclins in colon cancer and in cell lines from colon carcinomas.

Cyclins D1, D2 and D3 play important roles in cell proliferation and differentiation. Although their abnormal expression has been linked to cancer development and progression in a number of tissues, the expression of cyclin D2 and D3 proteins in colon cancer has not yet been characterised. In this study, we examined cyclin D1, D2 and D3 protein expression by Western blot analysis in tumour and adjacent normal colon tissues of 57 patients. In addition, we examined D-type cyclins protein expression in HT29 and LoVo39 cell lines from colon carcinomas, as a function of induced proliferation and differentiation. In both cell lines, the expression of the three D-type cyclins increased as a result of induced proliferation, whereas the expression of cyclin D3 increased as a result of induced differentiation. In colon tumours, cyclin D1 was overexpressed in 44%, cyclin D2 was overexpressed in 53% and cyclin D3 was overexpressed in 35% of the cases. We also found that in 16% of the cases, cyclin D3 protein expression was reduced in the tumour, as compared to the adjacent normal tissue. Examination of D-type cyclin protein overexpression in relation to the TNM stage of the tumours revealed that overexpression of cyclins D1 and/or D2, but not cyclin D3, is linked to colon carcinogenesis and that overexpression of cyclin D2 may be related to a higher TNM stage of the tumour.

Aged↗
PubMed1999

Prospective study of primary anastomosis without colonic lavage for patients with an obstructed left colon.

BACKGROUND: Traditionally, left-sided colon obstruction is managed by a multistaged defunctioning colostomy and resection. However, there is growing acceptance of one-stage primary resection and anastomosis with on-table antegrade irrigation. This paper presents a series of patients managed prospectively by primary anastomosis without intraoperative colonic lavage. METHODS: Emergency resection of acutely obstructed left-sided colonic carcinomas was performed. This was followed by primary anastomosis without on-table lavage after bowel decompression using a new technique. RESULTS: Fifty-eight consecutive, unselected patients underwent bowel decompression, resection and primary colocolic anastomosis. Only one patient developed a leak at the anastomotic site, requiring pelvic abscess drainage and transverse loop colostomy. One death occurred 12 h following surgery. Autopsy confirmed that this was due to myocardial infarction. Mean hospital stay was 9.8 days. CONCLUSION: Emergency surgery on the obstructed left colon can be carried out safely after decompression alone, without intraoperative colonic lavage.

Aged↗
PubMed2003

Molecular characterization of the microbial species that colonize human ileal and colonic mucosa by using 16S rDNA sequence analysis.

AIM: The aim of this study was to characterize the bacterial community adhering to the mucosa of the terminal ileum, and proximal and distal colon of the human digestive tract. METHODS AND RESULTS: Pinch samples of the terminal ileum, proximal and distal colon were taken from a healthy 35-year-old, and a 68-year-old subject with mild diverticulosis. The 16S rDNA genes were amplified using a low number of PCR cycles, cloned, and sequenced. In total, 361 sequences were obtained comprising 70 operational taxonomic units (OTU), with a calculated coverage of 82.6%. Twenty-three per cent of OTU were common to the terminal ileum, proximal colon and distal colon, but 14% OTU were only found in the terminal ileum, and 43% were only associated with the proximal or distal colon. The most frequently represented clones were from the Clostridium group XIVa (24.7%), and the Bacteroidetes (Cytophaga-Flavobacteria-Bacteroides) cluster (27.7%). CONCLUSION: Comparison of 16S rDNA clone libraries of the hindgut across mammalian species confirms that the distribution of phylogenetic groups is similar irrespective of the host species. Lesser site-related differences within groups or clusters of organisms, are probable. SIGNIFICANCE AND IMPACT: This study provides further evidence of the distribution of the bacteria on the mucosal surfaces of the human hindgut. Data contribute to the benchmarking of the microbial composition of the human digestive tract.

Adult↗
PubMed2003

Citrobacter rodentium translocated intimin receptor (Tir) is an essential virulence factor needed for actin condensation, intestinal colonization and colonic hyperplasia in mice.

Citrobacter rodentium infection of mice serves as a relevant small animal model to study enterohaemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) infections in man. Enteropathogenic E. coli and EHEC translocate Tir into the host cytoplasmic membrane, where it serves as the receptor for the bacterial adhesin intimin and plays a central role in actin condensation beneath the adherent bacterium. In this report, we examined the function of C. rodentium Tir both in vitro and in vivo. Similar to EPEC, C. rodentium Tir is tyrosine phosphorylated and is essential for actin condensation. Citrobacter Tir and EPEC Tir are functionally interchangeable and both require tyrosine phosphorylation to mediate actin rearrangements. In contrast, Citrobacter Tir supports actin nucleation in EHEC independent of tyrosine phosphorylation, while EHEC Tir cannot replace Citrobacter Tir for this function. This indicates that C. rodentium and EPEC use an actin nucleating mechanism different from EHEC. We also found that Tir is expressed and translocated into mouse enterocytes in vivo by C. rodentium during infections. This represents the first direct demonstration of a type III effector translocated in vivo into a natural host by any pathogen. In addition, we showed that Tir, but not its tyrosine phosphorylation, is essential for C. rodentium to colonize the large bowel and induce attaching/effacing (A/E) lesions and colonic hyperplasia in mice, and that both EPEC Tir and EHEC Tir can substitute for Citrobacter Tir for these activities in vivo. These results thus demonstrate that Tir is an essential virulence factor in this infection model. The data also show that the function of Tir tyrosine phosphorylation and its subsequent actin nucleating activity are not essential for C. rodentium colonization of the mouse gut nor for inducing A/E lesions and colonic hyperplasia, thereby uncoupling colonization and disease from actin condensation for this A/E pathogen.

Actins↗
PubMed1997

Colonic migrating motor complexes (CMMCs) in the isolated mouse colon.

Spontaneous contractions were recorded from the circular muscle layer at three sites along the isolated mouse colon. The interval between contractions was approximately 4.5 min. The mean duration of the contractions ranged from 26 sec in the distal colon to 45 sec in the proximal colon. Contractions migrating more than half the length of the colon were termed colonic migrating motor complexes (CMMCs). Over 90% of tissues demonstrated migration predominantly in an aboral direction. Hyoscine (10(-6) M) decreased the amplitude of the CMMCs by at least 40% but had no significant effect on the interval or duration of the CMMCs. Nifedipine (10(-6) M) significantly decreased the amplitude of the CMMCs by 95% but did not alter the duration or the interval between the CMMCs. Hexamethonium (5 x 10(-4) M) and tetrodotoxin (TTX; 2 x 10(-6) M) abolished all CMMC activity. TTX increased the resting tone of the preparations. Nitro-L-arginine (10(-4) M) increased the resting tone of the preparations and significantly decreased the interval between the CMMCs by approximately 80% but had no significant effect on the duration of the CMMCs. The results suggest CMMCs migrate predominantly in an aboral direction and are neurogenic in origin. Nitric oxide may be involved in maintaining inhibition of the muscle between CMMCs.

Animals↗
PubMed1996

Fine mapping of colon tumor susceptibility (Scc) genes in the mouse, different from the genes known to be somatically mutated in colon cancer.

The predisposition to colon cancer is multigenetically controlled in animals and probably also in humans. We have analyzed the multigenic control of susceptibility to 1,2-dimethylhydrazine-induced colon tumors in mice by using a set of 20 homozygous CcS/Dem recombinant congenic strains, each of which contains a different random subset of approximately 12.5% of genes from the susceptible strain STS/A and 87.5% of genes from the relatively resistant strain BALB/cHeA. Some CcS/Dem strains received the alleles from the susceptible strain STS/A at one or more of the multiple colon tumor susceptibility loci and are susceptible, whereas others are resistant. Linkage analysis shows that these susceptibility genes are different from the mouse homologs of the genes known to be somatically mutated in human colon cancer (KRAS2, TP53, DCC, MCC, APC, MSH2, and probably also MLH1). Different subsets of genes control tumor numbers and size. Two colon cancer susceptibility genes, Scc1 and Scc2, map to mouse chromosome 2. The Scc1 locus has been mapped to a narrow region of 2.4 centimorgans (90% confidence interval).

1,2-Dimethylhydrazine↗
PubMed1999

The colonic H+,K+-ATPase functions as a Na+-dependent K+(NH4+)-ATPase in apical membranes from rat distal colon.

Recent studies have suggested that the colonic H+,K+-ATPase (HKalpha2) can secrete either Na+ or H+ in exchange for K+. If correct, this view would indicate that the transporter could function as either a Na+ or a H+ pump. To investigate this possibility a series of experiments was performed using apical membranes from rat colon which were enriched in colonic H+,K+-ATPase protein. An antibody specific for HKalpha2 was employed to determine whether HKalpha2 functions under physiological conditions as a Na+-dependent or Na+-independent K+-ATPase in this same membrane fraction. K+-ATPase activity was measured as [gamma-32P]ATP hydrolysis. The Na+-dependent K+-ATPase accounted for approximately 80% of overall K+-ATPase activity and was characterized by insensitivity to Sch-28080 but partial sensitivity to ouabain. The Na+-independent K+-ATPase activity was insensitive to both Sch-28080 and ouabain. Both types of K+-ATPase activity substituted NH4+ for K+ in a similar manner. Furthermore, our results demonstrate that when incubated with native distal colon membranes, the blocking antibody inhibited dramatically Na+-dependent K+-ATPase activity. Therefore, these data demonstrate that HKalpha2 can function in native distal colon apical membranes as a Na+-dependent K+-ATPase. Elucidation of the role of the pump as a transporter of Na+ versus H+ or NH4+ versus K+ in vivo will require additional studies.

Adenosine Triphosphatases↗
PubMedDate not supplied

Colonic motility diagnosis based on colonic pressure.

Manometry of the alimentary tract is a valuable and widely used means to evaluate and diagnose the function of the alimentary tract. However, the measurement can be inconvenient due to the invasive method used, and the many factors affecting results. Research on colonic pressure data is even more insufficient. This paper deals with colonic pressure data via an improved method ensuring that pressure data of the whole colon is available. The data is analysed based on the learning vector quantization (LVQ) method. Testing results show that this method distinguishes the normal data and the abnormal data, consistently with the original diagnoses. This method can serve as an assistant diagnosis of colonic motility and contributes to further research on colonic motility based on pressure data.

Adolescent↗
PubMed2002

Frequency of proliferation, apoptosis, and their ratio during rat colon carcinogenesis and their characteristic pattern in the dimethylhydrazine-induced colon adenoma and carcinoma.

The imbalance between the cell proliferation and cell loss plays a crucial role in the carcinogenesis and tumor progression. However, the direction of these changes is still the matter of discussion. Thus, the aim of this study was to evaluate the proliferative activity, apoptotic activity, and proliferation/apoptosis ratio (P/A) assessed every 6 weeks in the colonic epithelium during 21 weeks of dimethylhydrazine (DMH) treatment in male Wistar rats. Moreover, it is necessary to answer the question whether these analyzed parameters correlate with the grade of differentiation or dysplasia of the induced tumors. It was found that DMH administration enhanced the proliferation in week 12 and 18 when compared with week 6. The proliferation in the control group did not change during the study. Up to week 12 of the experiment, there were no statistically significant differences between proliferative activity in the control and DMH-treated groups. In week 18, the proliferation in DMH-treated group was higher than in the control group. At all time points of the study, the apoptotic activity in the DMH-treated groups was significantly higher than in controls and in both groups, they dropped during the study. In the control group, apoptotic activity decreased in week 18 and was lower in comparison to that in week 6 and 12. In the group treated with DMH, apoptosis dropped at week 12 and was lower than in week 6. The P/A ratio did not change during the study in the control group, but increased in the DMH-treated group. After 21 weeks of DMH administration, 28 cases of colon adenocarcinoma and nine cases of colon adenoma were obtained and classified according to the WHO classification (1989) for human colon tumors. The adenocarcinomas were divided into four groups: well, moderately, poorly differentiated, and signet-ring cell carcinoma. The colon adenomas were divided into three groups: adenoma with mild, moderate, and severe grade of dysplasia. The proliferative activity in signet-ring cell carcinoma was significantly smaller than in well, moderately, and poorly differentiated adenocarcinoma and apoptotic activity was smaller than in well-differentiated adenocarcinoma. A weak (statistically nonsignificant) negative correlation was also observed between the proliferative and apoptotic activity in adenocarcinoma or adenoma and their grade of dedifferentiation or dysplasia, respectively.

Adenoma↗
PubMed1992

Colonic aberrant crypt foci are associated with increased expression of c-fos: the possible role of modified c-fos expression in preneoplastic lesions in colon cancer.

Aberrant crypt foci represent the earliest detectable lesions of colon cancer. The expression of c-fos in these aberrant crypts was determined by in situ hybridization and immunohistochemistry. These lesions were induced in the colonic epithelium with azoxymethane using the rat model system. Expression of c-fos was markedly increased in the aberrant colonic crypts. Increases of approximately 60 and approximately 70% in the proportion of epithelial cells labelled were observed in the early and advanced aberrant crypts respectively. This was found to be statistically significant (P less than 0.001). Consistent with cell proliferation patterns in the colonic crypts, the epithelial cells of the lower crypt had greater levels of c-fos mRNA than those of the upper part of the crypts. In addition, immunohistochemical staining with c-fos polyclonal antibodies demonstrated increased levels of c-fos protein in aberrant crypts. This combined approach using in situ hybridization and immunohistochemistry has shown that increased c-fos expression at the RNA level in these lesions is associated with increased amounts of c-fos protein. Since c-fos has been implicated in the process of cell proliferation and differentiation, modifications in its expression may be significant to understanding the mechanisms whereby preneoplastic lesions transform to neoplastic lesions in colon cancer.

Animals↗
PubMed1995

Use of HT-29, a cultured human colon cancer cell line, to study the effect of fermented milks on colon cancer cell growth and differentiation.

Epidemiological and in vivo and in vitro experimental studies have suggested that fermented milks may interfere with the emergence and/or the development of colon cancer. The results, however, remain inconclusive. This prompted us to develop a new approach based on the use of HT-29, a cultured human colon cancer cell line, to study at the cellular level the effect of fermented milks on colon cancer cell growth and differentiation characteristics. Undifferentiated HT-29 cells have been grown in the continuous presence of milks fermented by one of the following bacterial populations: Lactobacillus helveticus, Bifidobacterium, L.acidophilus or a mix of Streptococcus thermophilus and L. bulgaricus. Penicillin G was added to the cell culture medium, resulting in a complete blockade of bacterial growth without significant effect on bacterial viability. One out of the four bacteria species studied, namely L.acidophilus, was without effect on both cell growth and differentiation. The three other bacterial strains induced a significant, although variable, reduction in the growth rate of HT-29 cells, which resulted in a 10-50% decrease in the cell number at steady-state (i.e. at cell confluency). The most efficient strains in lowering the HT-29 growth rate were L. helveticus and Bifidobacterium. Concomitantly, the specific activities of dipeptidyl peptidase IV (DPP IV), a sensitive and specific marker of HT-29 cell differentiation, and that of three other brush border enzymes (sucrase, aminopeptidase N and alkaline phosphatase) were significantly increased, thus suggesting that these cells may have entered a differentiation process. Altogether, these results indicate that the use of cultured colon cancer cells may be a useful tool to further study the effect of fermented milks on colon cancer and that bacterial strains may exert a different and specific effect on cancer cell growth and differentiation when used in fermented milk products.

Animals↗
PubMed2001

Insulin-like growth factor-II renders LIM 2405 human colon cancer cells resistant to butyrate-induced apoptosis: a potential mechanism for colon cancer cell survival in vivo.

Butyrate has potent anti-tumorigenic effects on many colon cancer cell lines, including inhibition of growth and promotion of apoptosis in vitro. Nevertheless, despite the butyrate concentration in the colonic lumen being sufficient to result in the death of almost all cells in vitro, colon cancers still develop and grow in vivo, suggesting that cancer cells must develop mechanisms by which they escape the effects of butyrate observed in vitro. Insulin-like growth factor-II (IGF-II) is an autocrine growth factor in many colon cancer cells. The aim of this study was to determine whether IGF-II influences butyrate-mediated apoptosis in LIM 2405 human colon cancer cells. Butyrate and trichostatin A, both of which are histone deacetylase inhibitors although the latter is more specific, induced apoptosis as determined by floating cell counting, Hoechst 33258 staining, DNA laddering and a cell death detection ELISA. IGF-II inhibited the effects of both agents. Butyrate but not trichostatin A also induced LIM 2405 cell migration. In contrast to the above results, IGF-II enhanced butyrate-induced cell migration. Levels of IGF binding protein-3 (IGFBP-3), which may induce apoptosis by IGF-dependent or -independent mechanisms, were increased by butyrate and trichostatin A; IGF-II augmented this effect. It is therefore unlikely that IGFBP-3 mediates butyrate-induced apoptosis. We suggest that IGF-II inhibits the pro-apoptotic effect of butyrate downstream of histone deacetylase inhibition. In contrast, IGF-II promotes histone deacetylase-dependent IGFBP-3 expression and histone deacetylase-independent migration. IGF-II may promote tumour growth by mediating the development of resistance to the pro-apoptotic effects of butyrate.

Apoptosis↗
PubMed1983

Small-cell undifferentiated carcinoma of the colon. A clinicopathological study of five cases and their association with colonic adenomas.

Colonic small-cell undifferentiated carcinoma (SCUC) is an extremely aggressive neoplasm. We describe five patients with colonic SCUC and review five additional, well-documented cases. The longest known duration of survival is 14 months and all patients with follow-up of this duration have died of disease. Regional lymph nodes are invariably involved at the time of diagnosis and when distant metastases were present, the liver was always affected. Four of our cases of SCUC arose in association with colonic adenomas and in two of these the SCUC component was confined to the superficial submucosa. Yet, both produced regional metastases and one had massive hepatic involvement. Ultrastructurally, colonic SCUC exhibits divergent, predominantly neuroendocrine differentiation. The ultrastructural features and association with colonic adenomas suggest an endodermal rather than neuroectodermal derivation.

Adenoma↗
PubMed1994

The colonic air insufflation test indicates a colonic cause of abdominal pain. An aid in the management of irritable bowel syndrome.

We evaluated a standardized colonic air insufflation test in patients investigated for abdominal pain; 195 patients were evaluable. Of 164 patients with functional abdominal pain, 100 of the 128 (78%) with irritable bowel syndrome diagnosed on the basis of two or more Manning criteria (group A) had positive tests, compared with 19 of the 36 (53%) with functional abdominal pain not satisfying the diagnostic criteria for irritable bowel syndrome (group B). Eight of the 10 patients (80%) with structural colonic disease had positive tests (group C), and 3 of the 21 patients (14%) with structural noncolonic causes of abdominal pain (group D) had positive tests (group A vs. B, A vs. D, and C vs. D, p < 0.01). The air insufflation test had a sensitivity of 78% for the diagnosis of colonic pain and a specificity of 61%. The positive predictive value was 83% and the negative predictive value 54%. Sequential tests by two independent observers on 26 consecutive patients showed no interobserrer variation. The colonic air insufflation test warrants further evaluation as an adjunct to the Manning criteria in the diagnosis of irritable bowel syndrome. It can also serve as an investigative tool to define a subset of patients with functional abdominal pain who do not fulfill the current criteria for irritable bowel syndrome yet whose pain actually originates from the colon.

Abdominal Pain↗
PubMed1990

Quantitative contribution of factors regulating rat colonic crypt epithelium: role of parenteral and enteral feeding, caloric intake, dietary cellulose level and the colon carcinogen DMH.

To elucidate the role and quantitative contribution of several exogenous factors which may regulate colon crypt mitotic activity, proliferative zone height (PZH) and crypt height, groups of rats were subjected to various feeding regimens both with and without treatment with the colon carcinogen, 1,2-dimethylhydrazine (DMH). The rats were divided into two major groups and one group was given eight weekly injections of DMH base at 9.5 mg kg-1 body weight. Throughout this period and for two additional weeks the rats were isocalorically fed either a defined nutritionally complete diet with different levels of dietary cellulose or they were parenterally (i.v.) fed a nutritionally complete liquid formula with different caloric levels. The rats were then injected with colchicine 3 h prior to sacrifice to arrest and to collect dividing cells at metaphase. The results of multiple regression analysis of all data were interpreted to indicate that parenteral feeding caused dramatic suppression of the colon crypt height (CH) and of the number of metaphase figures per crypt (MC). Increased cellulose intake stimulated CH but suppressed MC. The CH was also stimulated by DMH. CH was positively correlated to PZH and MC. The MC was suppressed by cellulose intake and negatively correlated to PZH but was positively correlated to CH. The PZH was positively correlated to CH. These findings were related to the role of luminal food, functional workload, kcal intake and treatment with DMH on the measured colon crypt parameters. A quantitative assessment of factors that regulate the measured colonic crypt parameters was accomplished.

1,2-Dimethylhydrazine↗
PubMed2006

Rural-urban differences in colon cancer risk in blacks and whites: the North Carolina Colon Cancer Study.

CONTEXT: Geographic and racial variations in cancer incidence have been observed. Studies of colorectal carcinoma indicate a higher incidence and mortality rate for blacks than for whites in the United States. PURPOSE: We evaluated the effect of rural versus urban residence on colon cancer risk and stage of disease at diagnosis in blacks and whites. METHODS: Interviews were conducted with 558 colon cancer cases and 952 controls enrolled in the North Carolina Colon Cancer Study, a population-based case-control study of blacks and whites residing in 33 contiguous counties. FINDINGS: Residence in a rural area was associated with increased colon cancer risk (odds ratio, 1.4; 95% confidence interval, 1.1-1.8). This association was no longer significant after controlling for recent use of colorectal cancer screening tests (odds ratio, 1.2; 95% confidence interval, 0.9-1.6). Risk estimates were not modified by race nor were they markedly different for extent of disease at diagnosis. However, colorectal cancer screening rates were lower for blacks than for whites. CONCLUSION: Our findings suggest that rural blacks and whites are at increased risk of colon cancer regardless of stage of disease at diagnosis than their urban counterparts; this relationship may be mediated by screening behavior.

Black or African American↗