Dietary acrylamide and the risk of pancreatic cancer in the International Pancreatic Cancer Case-Control Consortium (PanC4).

Background: Occupational exposure to acrylamide was associated with excess mortality from pancreatic cancer, though in the absence of dose-risk relationship. Few epidemiological studies have examined the association between acrylamide from diet and pancreatic cancer risk. Patients and methods: We considered this issue in a combined set of 1975 cases of pancreatic cancer and 4239 controls enrolled in six studies of the Pancreatic Cancer Case-Control Consortium (PanC4). We calculated pooled odds ratios (ORs) and their 95% confidence intervals (CI) by estimating study-specific ORs through multivariate unconditional logistic regression models and pooling the obtained estimates using random-effects models. Results: Compared with the lowest level of estimated dietary acrylamide intake, the pooled ORs were 0.97 (95% CI, 0.79-1.19) for the second, 0.91 (95% CI, 0.71-1.16) for the third, and 0.92 (95% CI, 0.66-1.28) for the fourth (highest) quartile of intake. For an increase of 10 µg/day of acrylamide intake, the pooled OR was 0.96 (95% CI, 0.87-1.06), with heterogeneity between estimates (I2 = 67%). Results were similar across various subgroups, and were confirmed when using a one-stage modelling approach. Conclusions: This PanC4 pooled-analysis found no association between dietary acrylamide and pancreatic cancer.

Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium.

BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications. PATIENTS AND METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years). CONCLUSION: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.

Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Peptic ulcer and its treatments have been associated to pancreatic cancer risk, although the evidence is inconsistent. METHODS: We pooled 10 case-control studies within the Pancreatic Cancer Case-control Consortium (PanC4), including 4717 pancreatic cancer cases and 9374 controls, and estimated summary odds ratios (OR) using multivariable logistic regression models. RESULTS: The OR for pancreatic cancer was 1.10 [95% confidence interval (CI) 0.98-1.23] for history of ulcer (OR = 1.08 for gastric and 0.97 for duodenal ulcer). The association was stronger for a diagnosis within 2 years before cancer diagnosis (OR = 2.43 for peptic, 1.75 for gastric, and 1.98 for duodenal ulcer). The OR was 1.53 (95% CI 1.15-2.03) for history of gastrectomy; however, the excess risk was limited to a gastrectomy within 2 years before cancer diagnosis (OR = 6.18, 95% CI 1.82-20.96), while no significant increased risk was observed for longer time since gastrectomy. No associations were observed for pharmacological treatments for ulcer, such as antacids, H2-receptor antagonists, or proton-pump inhibitors. CONCLUSIONS: This uniquely large collaborative study does not support the hypothesis that peptic ulcer and its treatment materially affect pancreatic cancer risk. The increased risk for short-term history of ulcer and gastrectomy suggests that any such association is due to increased cancer surveillance.

Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction. PATIENTS AND METHODS: A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10,947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4). RESULTS: The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of >2 years between diagnoses (OR: 2.71, 95% CI: 1.96-3.74) and much stronger at intervals of ≤2 years (OR: 13.56, 95% CI: 8.72-21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (<65 years) pancreatic cancer cases showed stronger associations with previous (>2 years) pancreatitis (OR: 3.91, 95% CI: 2.53-6.04) than the older (≥65 years) cases (OR: 1.68, 95% CI: 1.02-2.76; P value for interaction: 0.006). CONCLUSIONS: Despite a moderately strong association between pancreatitis (diagnosed before >2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612-2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented.

Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved. METHODS: To evaluate the role of alcohol consumption in relation to pancreatic cancer, we conducted a pooled analysis of 10 case-control studies (5585 cases and 11,827 controls) participating in the International Pancreatic Cancer Case-Control Consortium. We computed pooled odds ratios (ORs) by estimating study-specific ORs adjusted for selected covariates and pooling them using random effects models. RESULTS: Compared with abstainers and occasional drinkers (< 1 drink per day), we observed no association for light-to-moderate alcohol consumption (≤ 4 drinks per day) and pancreatic cancer risk; however, associations were above unity for higher consumption levels (OR = 1.6, 95% confidence interval 1.2-2.2 for subjects drinking ≥ 9 drinks per day). Results did not change substantially when we evaluated associations by tobacco smoking status, or when we excluded participants who reported a history of pancreatitis, or participants whose data were based upon proxy responses. Further, no notable differences in pooled risk estimates emerged across strata of sex, age, race, study type, and study area. CONCLUSION: This collaborative-pooled analysis provides additional evidence for a positive association between heavy alcohol consumption and the risk of pancreatic cancer.

Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4).

BACKGROUND: To evaluate the dose-response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables. METHODS: We analyzed data from 12 case-control studies within the International Pancreatic Cancer Case-Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models. RESULTS: Compared with never smokers, the OR was 1.2 (95% confidence interval [CI] 1.0-1.3) for former smokers and 2.2 (95% CI 1.7-2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR=3.4 for ≥35 cigarettes per day, P for trend<0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR=2.4). No trend in risk was observed for age at starting cigarette smoking, whereas risk decreased with increasing time since cigarette cessation, the OR being 0.98 after 20 years. CONCLUSIONS: This uniquely large pooled analysis confirms that current cigarette smoking is associated with a twofold increased risk of pancreatic cancer and that the risk increases with the number of cigarettes smoked and duration of smoking. Risk of pancreatic cancer reaches the level of never smokers ∼20 years after quitting.

Cigar and pipe smoking, smokeless tobacco use and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Cigarette smoking is the best-characterized risk factor for pancreatic cancer. However, data are limited for other tobacco smoking products and smokeless tobacco. MATERIALS AND METHODS: We conducted a pooled analysis of cigar and pipe smoking and smokeless tobacco use and risk of pancreatic cancer using data from 11 case-control studies (6056 cases and 11,338 controls) within the International Pancreatic Cancer Case-Control Consortium (PanC4). Pooled odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated by unconditional multiple logistic regression models adjusted for study center and selected covariates. RESULTS: Compared with never tobacco users, the OR for cigar-only smokers was 1.6 (95% CI: 1.2-2.3), i.e. comparable to that of cigarette-only smokers (OR 1.5; 95% CI 1.4-1.6). The OR was 1.1 (95% CI 0.69-1.6) for pipe-only smokers. There was some evidence of increasing risk with increasing amount of cigar smoked per day (OR 1.82 for ≥ 10 grams of tobacco), although not with duration. The OR for ever smokeless tobacco users as compared with never tobacco users was 0.98 (95% CI 0.75-1.3). CONCLUSION: This collaborative analysis provides evidence that cigar smoking is associated with an excess risk of pancreatic cancer, while no significant association emerged for pipe smoking and smokeless tobacco use.

Saturated fat intake and prostate cancer aggressiveness: results from the population-based North Carolina-Louisiana Prostate Cancer Project.

BACKGROUND: Epidemiologic and laboratory evidence supports a role for cholesterol in prostate cancer (PC). Dietary saturated fat content impacts serum cholesterol levels. However, epidemiologic associations between saturated fat and PC aggressiveness are inconsistent. We hypothesized that high saturated fat intake would be associated with increased PC aggressiveness, and that statin use would modify this association. METHODS: Of 1854 PC cases in the North Carolina-Louisiana PC Project, 321 (17%) were classified as high aggressive (Gleason sum ⩾8, PSA>20 ng ml-1, or Gleason sum ⩾7 and clinical stage T3-4) or low/intermediate aggressive (all other cases). Using low/intermediate aggressive cases as the referent group, we examined the association between tertiles of total fat-adjusted saturated fat intake and high aggressive PC using logistic regression, overall and stratified by race and statin use. We examined total fat-adjusted polyunsaturated and monounsaturated fatty acids (PUFA and MUFA, respectively), trans fat and cholesterol intake in secondary analysis. RESULTS: High total fat-adjusted saturated fat intake was associated with an elevated odds ratio (OR) for aggressive PC (ORT3vsT1 1.51; 95% CI 1.10-2.06; P-trend=0.009), with an attenuated association in statin users (ORT3vsT1 1.16; 95% CI 0.67-2.01; P-trend=0.661) compared with non-users (ORT3vsT1 1.71; 95% CI 1.16-2.51; P-trend=0.053). High total fat-adjusted cholesterol intake was associated with aggressive PC in European Americans (ORT3vsT1 1.62; 95% CI 1.02-2.58; P-trend=0.056), but not African Americans (ORT3vsT1 0.92; 95% CI 0.60-1.42; P-trend=0.750). High total fat-adjusted PUFA was inversely associated with PC aggressiveness (ORT3vsT1 0.75; 95% CI 0.55-1.03), although this was not significant. No associations were found between total fat-adjusted MUFA or trans fat and PC aggressiveness. CONCLUSIONS: High total fat-adjusted saturated fat intake was associated with increased PC aggressiveness, with a suggestion of a stronger effect in men not using statins. The association between total fat-adjusted cholesterol intake and PC aggressiveness was most pronounced in European Americans.

Diet and chronic atrophic gastritis: a case-control study.

A hospital-based case-control study of gastric cancer precursor lesions was conducted in a high-risk black population in southern Louisiana. Ninety-three subjects with biopsy-proved advanced chronic atrophic gastritis were compared to two control series: a gastroscopy clinic series and a general hospital-admission series. Dietary case-control differences indicated a protective effect associated with fruit and vegetable intake and with dietary vitamin C and a risk elevation associated with milk consumption. The protective effect associated with consumption of fruits, vegetables, and vitamin C is consistent with findings for gastric cancer and with the etiologic hypothesis of intragastric nitrosation. A twofold increased risk was associated with cigarette smoking. Gastric juice pH, NO3-, and NO2- were determined for subjects undergoing gastroscopy, and comparisons were made between this high-risk U.S. group and a Colombian population with a much greater magnitude of risk; the latter had higher NO3- and NO2- levels. An increase in pH was associated with increasing severity of gastric lesions. Levels of pH and NO2- concentration were significantly correlated (P less than .0005); however, in Louisiana the large difference in NO2- concentration associated with pH elevation is not associated with histopathologic severity. Divergent trends with severity of lesions for NO3- concentration were seen in the two populations.

Dietary determinants of gastric cancer in south Louisiana inhabitants.

In south Louisiana, 391 recently diagnosed gastric cancer patients and an equal number of controls were interviewed. Questions asked covered residential and occupational histories, environmental exposures, tobacco use, diet, alcohol consumption, and pertinent demographic characteristics. Elevated relative risks were found for use of tobacco and alcohol products. Diet was found to be the main determinant of gastric cancer risk in south Louisiana. Both dietary patterns and dietary risk factors differed for blacks and whites, although fruits as a group and dietary vitamin C were found to exert strong protective effects for both blacks and whites. Consumption of smoked foods and homemade or home-cured meats increased risk of gastric cancer for blacks but not for whites. The findings are discussed in the light of the prevailing etiologic hypotheses.

Proliferative and antigenic modifications in human epithelial cells in chronic atrophic gastritis.

For the study of both proliferative and antigenic changes in epithelial cells in a disease predisposing to gastric cancer, endoscopic biopsy specimens were analyzed following removal from individuals with chronic atrophic gastritis (CAG); comparisons were made with specimens from normal gastric mucosa. All subjects were from Nariño, Colombia, the population of which has a high age-adjusted incidence of gastric cancer (150/100,000 population) occurring mainly in gastric antrum. After pulse incubation of biopsy specimens with tritiated thymidine ([3H]dThd), microautoradiographic distributions of [3H]dThd-labeled cells in the epithelial lining of gastric pits were correlated with expression of serologically defined gamma-fetal antigen (FA) as a second marker. Measurements were done both in gastric corpus and in antrum for entire gastric pits and over multiple gastric pit compartments. Total numbers of cells per gastric pit column did not differ between the normal and the CAG specimens either in corpus or in antrum; however, both in corpus and in antrum mean numbers of [3H]dThd-labeled cells per gastric pit column and labeling index were almost twice as large for the CAG population (P less than .006). Labeling index differences also were significant over most gastric pit compartments (P less than .02). In antrum gamma-FA-positive lesions had an expanded proliferative compartment with labeling indices significantly greater than those of antigen-negative lesions (P less than .02). This correlation did not extend to biopsy specimens obtained from corpus of stomach where the frequency of carcinoma is low. Findings indicate a hyperproliferative state in CAG compared to the proliferative state in normal gastric mucosa and, in gastric antrum, a further correlation with expression of gamma-FA in hyperproliferating cells. The two markers can be used to aid definition of the gastric mucosa in a disease associated with the development of gastric cancer and in prophylactic dietary intervention programs.

Brain tumor mortality risk among men with electrical and electronics jobs: a case-control study.

Brain tumor risk associated with electrical and electronics jobs and with occupational exposure to microwave and radiofrequency (MW/RF) electromagnetic radiation was evaluated with the use of data from a death certificate-based case-control study of brain tumors and occupational risk factors in northern New Jersey, Philadelphia, PA, and southern Louisiana. Next-of-kin of 435 white men who died of a primary brain tumor and of 386 controls who died from other causes were interviewed to obtain information on lifetime occupational history and other factors that might be related to excess brain tumor risk. The relative risk (RR) for all brain tumors was elevated among men exposed to MW/RF radiation [RR = 1.6; 95% confidence interval (Cl) = 1.0, 2.4] and was significantly elevated among men exposed for 20 or more years. All of the excess risk for MW/RF radiation-exposed subjects was derived from jobs that involved the design, manufacture, repair, or installation of electrical or electronic equipment (RR = 2.3; 95% Cl = 1.3, 4.2), while risk of brain tumors among MW/RF radiation-exposed subjects who never worked in electrical or electronics jobs was not elevated (RR = 1.0; 95% Cl = 0.5, 1.9). Furthermore, risk was elevated for electronics workers who were considered to have no exposure to MW/RF radiation. Among electrical and electronics workers, risk was highest for engineers, teachers, technicians, repairers, and assemblers combined (RR = 3.9; 95% Cl = 1.6, 9.9) and was limited to excess risk from astrocytic tumors (RR = 4.6; 95% Cl = 1.9, 12.2). Risk of astrocytic tumors among these electronics manufacture and repair workers increased with duration of exposure to tenfold among those employed for 20 or more years. Among electricians and power and telephone linemen combined (electrical tradesmen), the RR for astrocytic tumors was slightly elevated, but not statistically significant (RR = 1.8), and showed no consistent evidence of a duration-response relationship. Electrical tradesmen are exposed to extremely low frequency electromagnetic radiation, while men in some jobs associated with electronics manufacture and repair are exposed to electromagnetic radiation in the very high frequency and ultra-high frequency ranges and also may be exposed to soldering fumes, solvents, and a variety of other chemicals.

Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy.

BACKGROUND: Previous research has identified a high risk of gastric carcinoma as well as a high prevalence of cancer precursor lesions in rural populations living in the province of Nariño, Colombia, in the Andes Mountains. METHODS: A randomized, controlled chemoprevention trial was conducted in subjects with confirmed histologic diagnoses of multifocal nonmetaplastic atrophy and/or intestinal metaplasia, two precancerous lesions. Individuals were assigned to receive anti-Helicobacter pylori triple therapy and/or dietary supplementation with ascorbic acid, beta-carotene, or their corresponding placebos. Gastric biopsy specimens taken at baseline were compared with those taken at 72 months. Relative risks of progression, no change, and regression from multifocal nonmetaplastic atrophy and intestinal metaplasia were analyzed with multivariate polytomous logistic regression models to estimate treatment effects. All statistical tests were two-sided. RESULTS: All three basic interventions resulted in statistically significant increases in the rates of regression: Relative risks were 4.8 (95% confidence interval [CI] = 1.6-14.2) for anti-H. pylori treatment, 5. 1 (95% CI = 1.7-15.0) for beta-carotene treatment, and 5.0 (95% CI = 1.7-14.4) for ascorbic acid treatment in subjects with atrophy. Corresponding relative risks of regression in subjects with intestinal metaplasia were 3.1 (95% CI = 1.0-9.3), 3.4 (95% CI = 1.1-9.8), and 3.3 (95% CI = 1.1-9.5). Combinations of treatments did not statistically significantly increase the regression rates. Curing the H. pylori infection (which occurred in 74% of the treated subjects) produced a marked and statistically significant increase in the rate of regression of the precursor lesions (relative risks = 8.7 [95% CI = 2.7-28.2] for subjects with atrophy and 5.4 [95% CI = 1.7-17.6] for subjects with intestinal metaplasia). CONCLUSIONS: In the very high-risk population studied, effective anti-H. pylori treatment and dietary supplementation with antioxidant micronutrients may interfere with the precancerous process, mostly by increasing the rate of regression of cancer precursor lesions, and may be an effective strategy to prevent gastric carcinoma.

Case-control study of diet and mesothelioma in Louisiana.

Data were analyzed from a case-control interview study of malignant mesothelioma in Louisiana, which gathered information on usual diet and on lifetime occupational exposure to asbestos. Thirty-seven patients with malignant mesothelioma of the pleura (n = 32) or peritoneum (n = 5) were matched to controls according to age, sex, race, and factors related to case ascertainment (hospital and date of diagnosis, or parish and date of death). Twenty-one of the 37 cases were judged by masked occupational review to have been exposed to asbestos (57%), compared to seven of 37 controls (19%). Seven additional cases and 10 additional controls had occupational histories suggestive of asbestos exposure. With regard to usual diet before illness, cases reported less frequent consumption of homegrown produce (p = 0.005), cruciferous vegetables (p = 0.005), and all vegetables combined (p = 0.09) than did the controls. An estimate of usual carotene intake was also significantly lower in cases (p = 0.03). Dose-dependent reductions in risk were seen with increasing consumption of vegetables, especially cruciferous vegetables (p for trend = 0.013). These associations were not explained by differences in asbestos exposure as measured by the occupational review. The results indicate that consumption of vegetables or some vegetable-related constituent may have a protective effect on developing mesothelioma.

The relation of passive smoking to lung cancer.

To evaluate the role of passive smoking in the development of lung cancer among nonsmokers, data were pooled from three large incident case-control interview studies. Ninety-nine lung cancer cases and 736 controls never used any form of tobacco. Overall the adjusted odds ratio for lung cancer among nonsmokers ever living with a smoker was 0.8 (95% confidence interval, 0.5-1.3) rising to 1.2 among those exposed for 40 or more years. Persons living with a spouse who smoked cigarettes were at increased risk (adjusted odds ratio, 1.5; 95% confidence interval, 0.8-2.8). When adjusted for age and gender, there was a significant trend in risk with increasing amounts smoked per week by the spouse (P = 0.05) and with cumulative pack-years of exposure (P = 0.03). This effect was limited to females, especially older women whose husbands were heavy smokers. The elevated risk associated with spouse smoking was restricted to squamous and small cell carcinomas (odds ratio, 2.9; 95% confidence interval, 0.9-9.3), which provides additional evidence linking passive smoking to lung cancer.

Gastric precancerous process in a high risk population: cross-sectional studies.

The gastric precancerous process is evaluated in 1788 participants in a gastroscopy survey in the population of Nariño, Colombia, which has one of the highest gastric cancer incidence rates on record. A detailed histological classification is used, and a hierarchical distribution of lesions is described with the main stages being gland neck hyperplasia, atrophy (gland loss), intestinal metaplasia and dysplasia. Acute inflammation was not found to be a specific stage in the sequence but rather a common finding in all stages of the precancerous spectrum. Indices of disease progression for the different steps are calculated and found to increase with gastric pH and nitrate and nitrite content of the gastric juice. The effects of high pH and nitrite content are intimately correlated. Relative risks of specific lesions, namely, hyperplasia, atrophy, metaplasia, and dysplasia, increase linearly with higher pH, nitrate, and nitrite values in the gastric juice. The severity of atrophy correlates with the prevalence of metaplasia, suggesting a sequential relationship between the described stages, a finding supported by all parameters examined. The model of progression described may serve as a basis for comparisons with populations at different levels of gastric cancer risk but it fails to provide information concerning the time required for each change, which should be provided by follow-up (cohort) studies.

Gastric precancerous process in a high risk population: cohort follow-up.

In an attempt to characterize the natural history of the gastric precancerous process, 1422 residents of a high risk area of Nariño, Columbia, have been followed from 3-16 years (average 5.1) with repeated gastric biopsies, for a total of 7290 person-years. The original cohort consisted of 1788 individuals yielding a successful completion rate of 79.5%. Comparison of initial and subsequent biopsies revealed a very complex dynamic flow of both progressive and regressive events, suggesting sporadic environmental forces of modulation. One-time measurement of gastric juice, pH, and nitrite failed to predict future events in the gastric mucosa. The net loss of individuals whose gastric mucosa initially showed normal histology or superficial gastritis was 3.3%/year, representing a net gain of 1.7% for chronic atrophic gastritis, 0.9% for intestinal metaplasia, and 0.7% for dysplasia. The incidence rate of gastric cancer in this population was 0.16/100 person-years. The net rates of progression were higher and those of regression lower in older compared to younger individuals. The general pattern detected is that of a slow forward movement in the previously described hierarchical organization of precursor lesions. The presence of progressive as well as regressive changes and the slow pace of change offer special opportunities to inhibit progression through intervention strategies targeting previously identified etiological factors. The difficulties and opportunities offered by the long term follow-up studies as well as the congruency of the findings with current etiological hypotheses are discussed.

Inducible nitric oxide synthase, nitrotyrosine, and apoptosis in Helicobacter pylori gastritis: effect of antibiotics and antioxidants.

Helicobacter pylori infection is a known risk factor for gastric cancer. We hypothesized that H. pylori infection would lead to the sustained production of the reactive nitrogen species nitric oxide and peroxynitrite as part of the host immune response. We further hypothesized that H. pylori infection would lead to increased apoptosis of gastric epithelial cells, possibly in response to free radical-mediated DNA damage. Using immunohistochemistry, we stained and scored gastric antral biopsies from 84 Colombian patients with nonatrophic gastritis before and after treatment for H. pylori infection. We examined expression of inducible nitric oxide synthase (iNOS); nitrotyrosine, a marker for peroxynitrite; and DNA fragmentation, a marker for apoptosis. Patients were treated with triple therapy (amoxicillin, 500 mg three times a day for 2 weeks; metronidazole, 400 mg three times a day for 2 weeks; and bismuth subsalicylate, 262 mg four times a day for 2 weeks, followed by 262 mg every day for 4-12 months). Eradication of H. pylori infection resulted in a significant reduction in iNOS and nitrotyrosine staining and a marginally significant reduction in apoptosis. Dietary supplementation with beta-carotene (30 mg every day for 4-12 months) resulted in a significant decrease in iNOS staining. Supplementation with ascorbic acid (1 g twice a day for 4-12 months) led to a significant reduction in nitrotyrosine staining. In patients supplemented with either ascorbic acid or beta-carotene, there was a trend toward a reduction in apoptosis, but this was not statistically significant. We conclude that H. pylori infection is accompanied by the formation of endogenous reactive nitrogen intermediates, which may contribute to DNA damage and apoptosis. In addition to antimicrobial therapy, dietary supplementation with beta-carotene and ascorbic acid may prevent the formation of these potential carcinogens.

The effect of alcohol on the risk of lung cancer in Uruguay.

A hospital-based case-control study of the association between alcohol drinking and lung cancer was carried out in Uruguay between January 1988 and December 1990. The sample included 327 men with lung cancer and 350 male controls. Personal interviews were conducted in the Institute of Oncology by trained personnel using a structured questionnaire. The results showed a significant positive association between beer intake and the risk of lung cancer. The odds ratio for beer drinkers in the highest quartile was 3.4 (95% confidence limits, 1.3-6.6) after adjustment for tobacco. The association between beer and lung cancer was consistent for all the cell types, analyzed separately. A moderate effect for total alcohol consumption was also observed, with a relative risk of 2.2 for those subjects in the highest quartile.