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S R Hamilton

Publications and source records attributed to S R Hamilton.

At least 181 records · Page 10Linked to original sources
PubMed1988

Alpha-difluoromethylornithine-induced inhibition of growth of autochthonous experimental colonic tumors produced by azoxymethane in male F344 rats.

Ornithine decarboxylase, the first regulatory enzyme in polyamine biosynthesis, is inhibited by alpha-difluoromethylornithine (DFMO), a specific enzyme-activated irreversible inhibitor. DFMO has been shown previously to inhibit experimental colonic tumorigenesis in rodents given the large bowel carcinogen azoxymethane or dimethylhydrazine. Therefore, we assessed the effects of DFMO on growth of established autochthonous experimental colonic tumors. Ten-wk-old male F344 rats were given 10 weekly s.c. injections of azoxymethane, 10 mg/kg. Starting 5 wk after the last dose, colonoscopy to the splenic flexure was performed weekly with a pediatric fiberoptic bronchoscope. When a tumor was visualized, its growth was assessed by computer image analysis of weekly colonoscopic photographs which included a scale. After two measurements for baseline tumor growth, the tumor-bearing rats were assigned in predetermined alternating sequence to the DFMO group (n = 26) or control group (n = 28). DFMO, 30 mg/ml (3%), was given in drinking water for 4 wk, resulting in mean weekly intake of 16 +/- 1 (SE) to 18 +/- 1 mg of DFMO/g of body weight. Control rats were pair-fed, resulting in reduced body weights comparable to DFMO rats. DFMO dramatically inhibited tumor growth, beginning in the first week of administration: mean tumor volume of DFMO rats reached only 7.0 +/- 2.0 mm3 compared with 17.4 +/- 3.2 mm3 in controls (P less than 0.02); and tumors in three DFMO rats disappeared. Mean change in tumor volume in DFMO rats was less than controls during all 4 wk of administration, although there was a suggestion of escape from DFMO suppression of tumor growth in the last 2 wk. At necropsy, tumor ornithine decarboxylase activity was 115 +/- 22 pmol/h/mg of protein in DFMO rats as compared with 842 +/- 576 in controls. There was a suggestion of greater tumor desmoplasia in DFMO rats, but tumor differentiation, depth of invasion, inflammation, and labeling index with tritiated thymidine showed no statistically significant differences between the DFMO and control groups. Our findings suggest that (a) ornithine decarboxylase plays a key role in growth of autochthonous experimental colonic tumors, and (b) DFMO may have potential for chemotherapy and chemoprophylaxis of colorectal neoplasms in human beings.

Animals↗
PubMed1988

Genetic alterations during colorectal-tumor development.

Because most colorectal carcinomas appear to arise from adenomas, studies of different stages of colorectal neoplasia may shed light on the genetic alterations involved in tumor progression. We looked for four genetic alterations (ras-gene mutations and allelic deletions of chromosomes 5, 17, and 18) in 172 colorectal-tumor specimens representing various stages of neoplastic development. The specimens consisted of 40 predominantly early-stage adenomas from 7 patients with familial adenomatous polyposis, 40 adenomas (19 without associated foci of carcinoma and 21 with such foci) from 33 patients without familial polyposis, and 92 carcinomas resected from 89 patients. We found that ras-gene mutations occurred in 58 percent of adenomas larger than 1 cm and in 47 percent of carcinomas. However, ras mutations were found in only 9 percent of adenomas under 1 cm in size. Sequences on chromosome 5 that are linked to the gene for familial adenomatous polyposis were not lost in adenomas from the patients with polyposis but were lost in 29 to 35 percent of adenomas and carcinomas, respectively, from other patients. A specific region of chromosome 18 was deleted frequently in carcinomas (73 percent) and in advanced adenomas (47 percent) but only occasionally in earlier-stage adenomas (11 to 13 percent). Chromosome 17p sequences were usually lost only in carcinomas (75 percent). The four molecular alterations accumulated in a fashion that paralleled the clinical progression of tumors. These results are consistent with a model of colorectal tumorigenesis in which the steps required for the development of cancer often involve the mutational activation of an oncogene coupled with the loss of several genes that normally suppress tumorigenesis.

Adenoma↗
PubMed1988

Inhibition by dietary ethanol of experimental colonic carcinogenesis induced by high-dose azoxymethane in F344 rats.

Epidemiological studies have shown an association between consumption of alcoholic beverages and increased occurrence of large bowel carcinoma, but studies in experimental models of colonic carcinogenesis have produced conflicting results. We assessed the effects of chronic dietary ethanol consumption during the preinduction and induction phase (period of acclimatization and carcinogen administration) in a high-dose azoxymethane-treated rat model (14 mg/kg/wk for 10 wk). Ten-wk-old male Fischer 344 rats were given 33% of calories as ethanol or no ethanol (controls). Pair-feeding with Lieber-DeCarli-type liquid diets provided comparable total carbohydrates, proteins, fats, and calories. After 3 wk of dietary acclimatization, injections of azoxymethane (AOM) were given s.c. to all rats in Wk 1 to 10. At necropsy in Wk 25, dramatic suppression of gastrointestinal tumorigenesis was evident in the ethanol-fed group: the prevalence of colonic tumors was 5% as compared with 91% in controls; and the prevalence of small bowel tumors was 0% versus 74% (P less than 0.0001). In an analogous study of [14C]AOM metabolism, exhaled 14CO2 was decreased in the ethanol-fed rats, indicating suppression of AOM metabolism. Similarly, in the ethanol-fed rats the levels of the DNA adducts O6-methylguanine and 7-methylguanine 24 h after AOM injection were reduced in the colonic mucosa to 14 +/- 7% and 61 +/- 11% of controls and in the liver to 80 +/- 9% and 86 +/- 6 of controls. By contrast, rats changed from the ethanol diet to no-ethanol diet for 12 h prior to the dose of [14C]AOM metabolized the carcinogen at a faster rate than controls, indicating loss of suppression with cessation of ethanol intake along with induction of metabolizing enzymes; DNA adduct levels were reduced in the colonic mucosa to 90 +/- 13% and 76 +/- 9% of controls and in the liver to 81 +/- 6% and 85 +/- 3% of controls. Our findings indicate that dietary ethanol during the preinduction and induction phase of the AOM model dramatically inhibits tumorigenesis, even with high dosage of carcinogen, and suggest that: (a) inhibition of tumorigenesis may result from suppression of metabolic activation of AOM and the consequent reduced formation of DNA adducts during the induction (initiation) phase of the model; (b) these anti-initiation effects of ethanol are unrelated to the epidemiological association between consumption of alcoholic beverages and large bowel cancer; and (c) mechanisms of action of agents found to modulate carcinogenesis in experimental models should be determined before the results can be generalized to human beings.

Alkylation↗
PubMed1988

Prevalence and characteristics of Barrett esophagus in patients with adenocarcinoma of the esophagus or esophagogastric junction.

The prevalence and characteristics of Barrett esophagus in patients with adenocarcinoma of the esophagus or esophagogastric junction are uncertain. We studied 61 consecutive esophagogastrectomy specimens with adenocarcinoma, which were subjected to extensive histopathologic examination. Barrett esophagus was found in 64% of the cases (39 of 61), but had been recognized in only 38% of the patients with Barrett-associated carcinoma who had undergone preoperative endoscopy with biopsy (13 of 34). The median extent of Barrett esophagus with adenocarcinoma was 5 cm (range, 1 cm to 12 cm), and distinctive-type ("specialized") Barrett mucosa predominated (35 of 39; 90%). The Barrett adenocarcinomas were centered in the distal esophagus 2 cm +/- 0.3 cm above the esophagogastric junction. The patients with Barrett adenocarcinoma showed a striking predominance of white men (34 of 39; 87%) in contrast to gastric adenocarcinoma cases (21 of 69; 30%) and to Barrett patients without carcinoma or dysplasia (75 of 149; 50%), but similar to patients having adenocarcinoma of the esophagus or esophagogastric junction without demonstrable Barrett esophagus (16 of 22; 73%). Our findings suggest that most adenocarcinomas of the esophagus or esophagogastric junction are Barrett carcinomas, rather than gastric cardiac cancers or other types of esophageal adenocarcinoma; most Barrett adenocarcinomas occur in short segments of Barrett esophagus, which may be difficult to detect at endoscopy; and white men with Barrett esophagus may constitute a clinically identifiable at-risk group suitable for surveillance.

Adenocarcinoma↗
PubMed1988

Reported binding of monoclonal antibody RAP-5 to formalin-fixed tissue sections is not indicative of ras p21 expression.

RAP-5 is a monoclonal antibody that has been shown to be immunoreactive with human ras gene product p21 in solid-phase radioimmunoassays and Western blots. RAP-5 binding in excess of that of control monoclonal antibodies to formalin-fixed tissue sections of several types of human tumors has been reported, and this binding has been interpreted as indicating p21 expression. We report that high concentrations of control monoclonal antibodies duplicated exactly the immunohistochemical staining pattern of RAP-5 on formalin-fixed tissue sections and that RAP-5 staining was not competitively inhibited by either the portion of p21 it was raised against or by the thyroglobulin-conjugated peptide used as immunogen. In an enzyme-linked immunosorbent assay, RAP-5 also showed greater nonspecific binding to poly-L-lysine and to polystyrene wells than did control antibodies. We conclude that RAP-5 binding to formalin-fixed tissue sections is nonspecific and not indicative of p21 expression.

Antibodies, Monoclonal↗
PubMed1988

Pigmented ocular fundus lesions in the inherited gastrointestinal polyposis syndromes and in hereditary nonpolyposis colorectal cancer.

The authors studied pigmented ocular fundus lesions in three different forms of hereditary gastrointestinal polyposis and in hereditary nonpolyposis colorectal cancer. Congenital hypertrophy of the retinal pigment epithelium (CHRPE) was present in at least one member of 23 families with Gardner's syndrome. By contrast, CHRPE was not found in three families with familial polyposis coli, four families with hereditary nonpolyposis colorectal cancer, and three families with Peutz-Jeghers syndrome. Pigmented ocular fundus lesions of the CHRPE-type appear to be specific to Gardner's syndrome among inherited diseases with gastrointestinal polyposis.

Adenomatous Polyposis Coli↗
PubMed1988

Esophageal candidiasis. Managing an increasingly prevalent infection.

Esophageal candidiasis is an opportunistic infection that is being recognized increasingly often in certain patients, including those who have a neoplastic disease, are undergoing protracted antibiotic therapy, or hae acquired immunodeficiency syndrome (AIDS). Impaired cell-mediated immunity may predispose the patient to esophageal mucosal colonization, whereas chemotherapy-induced granulocytopenia may predispose to disseminated candidiasis. Esophageal candidiasis should be suspected in susceptible patients with complaints of substernal odynophagia or dysphagia. The diagnosis is confirmed by endoscopically directed mucosal biopsy. Esophagitis from other causes (eg. herpes simplex virus, cytomegalovirus, or bacterial infection) may develop concomitantly with esophageal candidiasis. Treatment is determined by the clinical and immune status of the patient. Amphotericin B (Fungizone) is administered to immunocompromised patients at risk for disseminated or deeply invasive candidiasis and is indicated in nongranulocytopenic patients whose symptoms prevent reliable administration of oral antifungal agents. Ketoconazole (Nizoral) may be administered to clinically stable nongranulocytopenic patients with esophageal candidiasis limited to the mucosa. Patients with AIDS and a history of esophageal candidiasis usually benefit from long-term suppression with an oral antifungal agent.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Diagnostic value of cytopathology in Barrett esophagus and associated carcinoma.

Barrett esophagus, the columnar-lined distal esophagus acquired as a consequence of chronic gastroesophageal reflux, is associated with the development of columnar epithelial dysplasia and esophageal adenocarcinoma. To determine the efficacy of cytopathology in identifying Barrett esophagus and related neoplasia, observations were compared on 150 esophageal cytology samples with concurrent endoscopic biopsy specimens. Sixty-six specimens that contained benign columnar epithelium in either cytologic or biopsy material were identified. Distinctive-type Barrett mucosa with incomplete intestinalization, considered diagnostic of Barrett esophagus, was found in 34 of 66 cases (52%) and was present only in cytologic material in 11 cases. Twenty-two specimens contained cardiac-type mucosa (present only in cytology in ten cases), a finding of uncertain significance due to lack of localization of the sample with respect to the gastroesophageal junction. Fundic-type mucosa was not observed in any specimen. Two cases of distinctive-type Barrett mucosa with columnar epithelial dysplasia were identified in both biopsy and cytology specimens. Among eight Barrett-associated carcinomas (seven adenocarcinomas and one squamous), cytologic material was diagnostic for malignancy in seven and highly suspicious in one. It was concluded that cytopathologic studies are a useful adjunct to biopsy histopathology in the diagnosis of Barrett esophagus and associated carcinoma. The role of cytopathology in the diagnosis of Barrett-related columnar epithelial dysplasia requires further study, and at present a cautious approach with biopsy confirmation is recommended.

Barrett Esophagus↗
PubMed1988

Gene amplification in malignant human gliomas: clinical and histopathologic aspects.

Gene amplification occurs in 45-50% of malignant human gliomas (MHG). In the present study, 64 genetically characterized gliomas were evaluated to determine if tumors with amplification of the epidermal growth factor receptor (EGFR), N-myc, c-myc, or gli genes had distinctive histopathologic features. There was no significant difference in age (p = 0.10) or gender (p = 0.78) between patients whose tumors contained amplified genes and those whose tumors did not exhibit this characteristic. Although the patients with amplified genes in their tumors survived slightly longer than patients whose tumors had no detectable gene amplification, these differences were not statistically significant (p = 0.21). The 28 tumors with amplification included 24/48 (50%) glioblastoma multiforme, 2/6 (33%) anaplastic astrocytomas and 2/5 (40%) gliosarcomas. No amplification was seen in one oligodendroglioma, three anaplastic mixed gliomas or one giant cell glioblastoma multiforme. Necrosis and endothelial proliferation were equally prevalent among tumors with and without amplification. Comparison of tumors with gene amplification and tumors without this characteristic revealed similar distributions of most morphologic cells types. Although prominent perivascular lymphocytic infiltrates were more frequent in tumors without amplification, this association was of borderline significance statistically. In situ hybridization of tumors with amplification using an EGFR mRNA probe showed intense labeling of different neoplastic cell types including fibrillary and protoplasmic astrocytes, gemistocytes, anaplastic cells, and multinucleated giant cells. Non-neoplastic cells such as hyperplastic endothelium within the tumors did not express detectable EGFR mRNA. These studies demonstrate that (a) cells with quite different morphology within the same tumor can contain the same genetic alteration; (b) tumors of identical histological appearance may have arisen and evolved by different molecular mechanisms; and (c) molecular analyses are necessary to evaluate gene amplification in MHG since this characteristic cannot be accurately predicted by the morphologic or clinical criteria used in this study.

Adult↗
PubMed1988

Intracytoplasmic plasma proteins in distended esophageal squamous cells (balloon cells).

Esophageal mucosal biopsy specimens frequently show numerous distended squamous cells with pale cytoplasm, which we term "balloon cells." These cells often occur in clusters, have a patchy distribution, and predominate in the prickle-cell layer in biopsies from patients with gastroesophageal reflux. We studied the immunohistochemical characteristics of balloon cells and their associated clinical findings. We demonstrated by immunoperoxidase technique that balloon cells contain intracytoplasmic albumin and immunoglobulin light chains and show reduced staining for keratin, suggesting cellular injury with resultant uptake of plasma proteins and fluid. Balloon cells were absent or sparse in esophageal mucosal biopsy specimens from 12 normal control persons, but were observed in 7 of 10 patients (70%) with gastroesophageal reflux confirmed by pH-probe test (P = 0.001 versus normal controls), in 16 of 25 patients (64%) with clinically suspected reflux (P less than 0.001), and in 4 of 5 patients with infectious or chemotherapy-associated esophagitis. However, no consistent association was found between balloon cells and the presence of the usual histopathologic criteria for epithelial injury, such as increased height of vascular tufts or width of basal zone. We conclude that balloon cells are most commonly observed in biopsy specimens from patients with various causes of esophageal injury. We propose that balloon cells may be a marker for epithelial injury, possibly even when other histopathologic criteria for injury are absent.

Adolescent↗
PubMed1987

Effects of chronic dietary ethanol on in vivo and in vitro metabolism of methylazoxymethanol and on methylazoxymethanol-induced DNA methylation in rat colon and liver.

We examined the metabolism of 14C-labeled methylazoxymethanol (MAM) in male F344 rats pair-fed for 21.0 days either a liquid control diet, an isocaloric liquid diet containing 6.6% ethanol by volume (continuous ethanol diet), or the ethanol diet for 20.5 days followed by the control diet for 0.5 day (interrupted ethanol diet). Compared to rats fed the control liquid diet, metabolism of [1,2-14C]MAM acetate to exhaled 14CO2 was inhibited by 25 to 42% in rats fed the continuous ethanol diet, but was initially stimulated by 90% in rats given the interrupted ethanol diet. MAM-induced DNA methylation, as reflected in 7-methylguanine and O6-methylguanine content 24 h after carcinogen administration, was inhibited in the colon mucosae of rats fed the interrupted ethanol diet by 52 to 54%, and an even greater inhibition (71 to 86%) of DNA methylation occurred in the colon mucosae of rats fed the continuous ethanol diet. Liver DNA methylation was significantly inhibited (by 32 to 42%) only in those rats fed the continuous ethanol diet. Liver microsomes isolated from rats fed the 3 diets metabolized MAM to formic acid and methanol in vitro, but liver microsomes from rats fed the continuous ethanol diet were 12 to 15 times more active than liver microsomes from rats fed the control diet. Liver microsomes isolated from rats fed the interrupted ethanol diet were only 3 to 5 times more active in MAM metabolism than liver microsomes from rats fed the control diet, indicating very rapid turnover of the ethanol-induced enzyme(s) catalyzing the oxidation of MAM. Although chronic ethanol feeding enhanced the activity of liver microsomes for MAM metabolism, ethanol was found to inhibit the reaction competitively. Hepatocytes isolated from rats fed the continuous ethanol diet were considerably more sensitive to MAM-induced unscheduled DNA synthesis than hepatocytes isolated from rats given the control liquid diet, indicating that the stimulation of MAM metabolism by dietary ethanol results in increased DNA damage, observable in an in vitro system. Thus, the increased metabolic activation of MAM, due to enzyme induction by ethanol which is observed in vitro, is not reflected in increased liver DNA methylation in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Alcoholism↗
PubMed1987

Clonal analysis of human colorectal tumors.

The clonal composition of human colorectal tumors was studied by means of restriction fragment length polymorphisms (RFLPs). First, X-linked RFLPs were used to examine the pattern of X chromosome inactivation in colorectal tumors of females. All 50 tumors examined showed monoclonal patterns of X chromosome inactivation; these tumors included 20 carcinomas as well as 30 adenomas of either familial or spontaneous type. Second, RFLPs of autosomes were used as clonal markers to detect the somatic loss or gain of specific chromosomal sequences in colorectal tumors. Among other changes, it was found that somatic loss of chromosome 17p sequences occurred in over 75 percent of the carcinomas examined, but such loss was rare in adenomas. These data support a monoclonal origin for colorectal neoplasms, and suggest that a gene on the short arm of chromosome 17 may be associated with progression from the benign to the malignant state.

Adenoma↗
PubMed1987

Clonal analysis using recombinant DNA probes from the X-chromosome.

It has been demonstrated that restriction fragment length polymorphisms of X-chromosome genes can be used in conjunction with methylation patterns to determine the clonal composition of human tumors. In this report, we show that several X-chromosome probes can be used for such analyses. In particular, probes derived from the hypoxanthine phosphoribosyltransferase gene and the phosphoglycerate kinase gene could be used for clonal analysis in over 50% of American females. The X-inactivation patterns observed with these probes were found to accurately reflect clonality in more than 95% of 92 tumors tested.

Alleles↗
PubMed1987

Effects of timing and quantity of chronic dietary ethanol consumption on azoxymethane-induced colonic carcinogenesis and azoxymethane metabolism in Fischer 344 rats.

Epidemiological studies have shown an association between consumption of alcoholic beverages and carcinoma of the large bowel, but studies in experimental models of colonic carcinogenesis have yielded conflicting results. We assessed the effects on azoxymethane-induced colonic carcinogenesis of both timing of chronic dietary ethanol consumption relative to carcinogen administration and quantity of ethanol consumption. Ten-week-old male Fischer 344 rats were given 11%, 22%, or 33% of calories as reagent ethanol or no ethanol by pair feeding with Lieber-DeCarli-type liquid diets providing comparable total carbohydrates, proteins, fats, and calories. Ten weekly s.c. injections of the bowel carcinogen azoxymethane (AOM), 7 mg/kg, were given to all rats in weeks 1-10. Three experimental groups were given their respective ethanol diet during acclimatization and AOM administration (preinduction and induction phases) and then were given the no-ethanol diet from week 11 until sacrifice in week 26 (postinduction phase). Three other groups received the no-ethanol diet during acclimatization and AOM administration and then were changed to their respective ethanol diet until sacrifice. The control AOM group received the no-ethanol diet throughout the study. Suppression of colonic tumorigenesis occurred in the groups with high levels of chronic dietary ethanol consumption during acclimatization and AOM administration: in the 33% and 22% diet groups, the prevalence of colonic tumors was 3% and 20% as compared with 50% in control (P less than 0.001 and P less than 0.02, respectively). Tumorigenesis in the left colon was more affected than in the right colon, as tumor prevalence in the left colon was decreased in both the 33% and 22% diet groups (0% in both versus 24% in control, P less than 0.005), whereas prevalence in the right colon was decreased only in the 33% diet group (3% versus 38%, P less than 0.001). By contrast, prevalence of colonic tumors in the 11% diet group was not significantly different from control. Chronic dietary ethanol consumption after AOM administration had no effect on tumor outcome, regardless of quantity of consumption. In an analogous study of [14C]AOM metabolism in rats fed the 33% diet during acclimatization and AOM administration, 14CO2 was exhaled at a slower rate than in rats fed no-ethanol diet (P = 0.05), indicating suppression of AOM metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Enhancement of rat liver microsomal metabolism of azoxymethane to methylazoxymethanol by chronic ethanol administration: similarity to the microsomal metabolism of N-nitrosodimethylamine.

We compared the metabolism of azoxymethane (AOM) and of N-nitrosodimethylamine (NDMA) by liver microsomes obtained from male F344 rats pair-fed for 3 weeks either a control liquid diet or an isocaloric liquid diet containing ethanol at a concentration of 6.6% by volume. High-performance liquid chromatographic analysis of the products of the microsomal metabolism of AOM showed that methylazoxymethanol was the only primary metabolite. While the formation of small (less than 4% of methylazoxymethanol) quantities of methanol and formaldehyde could also be detected in this reaction, these products could be accounted for almost entirely by the spontaneous decomposition of methylazoxymethanol. With NDMA as the substrate in the incubation system, the formation of methylamine, formaldehyde, methanol, and an additional, as yet unidentified metabolite was detected. Liver microsomes obtained from rats fed the ethanol-containing diet up to the time of sacrifice were 12-18 times more active in the metabolism of both AOM and NDMA than liver microsomes obtained from rats fed the control, ethanol-free diet for the same period. When rats fed the ethanol diet for 20.5 days were fed the control diet for 0.5 days and then sacrificed, only a 2- to 3-fold increase in the metabolism of both AOM and NDMA by liver microsomes was observed, indicating that cessation of ethanol intake results in a rapid decrease of the ethanol-induced metabolic enzymes. Hepatocytes isolated from ethanol-fed rats showed a significantly enhanced sensitivity to AOM- as well as to NDMA-induced unscheduled DNA synthesis, indicating that the increased rate of microsomal metabolism induced by ethanol is associated with enhanced carcinogen activation in vitro. The metabolism of AOM and NDMA by liver microsomes was inhibited to similar extents by carbon monoxide, pyrazole, sodium azide, aminoacetonitrile, imidazole, and ethanol. In addition, both ethanol and NDMA were found to inhibit competitively the microsomal metabolism of AOM. These results suggest that AOM and NDMA are metabolized by very similar, indeed perhaps the same rat liver microsomal enzyme(s).

Animals↗
PubMed1987

Increased risk of cancer in the Peutz-Jeghers syndrome.

The Peutz-Jeghers syndrome is an autosomal dominant hereditary disease characterized by hamartomatous polyps of the gastrointestinal tract and by mucocutaneous melanin deposits. The frequency of cancer in this syndrome has not been studied extensively. Therefore, we investigated 31 patients with the Peutz-Jeghers syndrome who were followed from 1973 to 1985. All cases of cancer were verified by histopathological review. Cancer developed in 15 of the 31 patients (48 percent)--gastrointestinal carcinomas in 4, nongastrointestinal carcinomas in 10, and multiple myeloma in 1. In addition, adenomatous polyps of the stomach and colon occurred in three other patients. The cancers were diagnosed when the patients were relatively young, but after the Peutz-Jeghers syndrome had been diagnosed (interval between diagnoses, 25 +/- 20 years; range, 1 to 64). According to relative-risk analysis, the observed development of cancer in the patients with the syndrome was 18 times greater than expected in the general population (P less than 0.0001). Our results suggest that patients with the Peutz-Jeghers syndrome have an increased risk for the development of cancer at gastrointestinal and nongastrointestinal sites.

Adolescent↗
PubMed1987

Effects of chronic dietary beer and ethanol consumption on experimental colonic carcinogenesis by azoxymethane in rats.

Epidemiological studies have shown an association between consumption of alcoholic beverages, particularly beer, and carcinoma of the large bowel, especially the rectum. We studied the effects of chronic dietary beer and ethanol consumption on experimental colonic carcinogenesis, fecal bile acid and neutral sterol levels, fecal bacterial flora, and colonic epithelial DNA synthesis. Ten-week-old male Fischer 344 rats were pair fed throughout the study with Lieber-DeCarli-type liquid diets providing comparable total carbohydrates, proteins, fats, and calories. The diets provided 23 or 12% of calories as alcohol in beer (Hi-Beer and Lo-Beer groups), 18 or 9% of calories as reagent ethanol (Hi-EtOH and Lo-EtOH groups), or no alcohol (control group). After 3 weeks of dietary acclimatization, 10 weekly s.c. injections of the bowel carcinogen azoxymethane, 7 mg/kg, were given (weeks 1-10). At necropsy in week 26, the high alcohol groups (Hi-Beer and Hi-EtOH) showed a significantly reduced incidence of tumors in the right colon (42 and 46% versus 81% in control, P less than 0.01 and P = 0.02) but no effect on left colonic tumorigenesis. By contrast, the low alcohol groups (Lo-Beer and Lo-EtOH) showed a trend toward increased incidence and proportion of tumors in the left colon (incidence of 42 and 35% versus 15% in control, P = 0.06 for Lo-Beer; 28 and 30% of tumors in left colon versus 11%, P = 0.08 and P = 0.07) but no effect on right colonic tumorigenesis. Numbers of right colonic tumors were inversely correlated with alcohol consumption of all rats (r = -0.350, P less than 0.001), but left colonic tumors were not correlated. Fecal bile acid and neutral sterol levels, fecal bacterial counts, and colonic epithelial DNA synthesis did not correlate with the effects of alcohol consumption on colonic tumorigenesis. Our findings suggest that: modulation of experimental colonic tumorigenesis by chronic dietary beer and ethanol consumption was due to alcohol rather than other beverage constituents; tumorigenesis in the right and left colon was affected differentially by the levels of alcohol consumption, reflecting complex interactions among the potential mechanisms for alcohol effects in the model used.

Alcohol Drinking↗