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.

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.

Long term follow up of patients treated for Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori infection induces progressive inflammatory changes in the gastric mucosa that may lead to gastric cancer. Understanding long term effects resulting from the cure of this infection is needed to design cancer prevention strategies. METHODS: A cohort of 795 adults with preneoplastic gastric lesions was randomised to receive anti-H pylori treatment and/or antioxidants. At the end of six years of intervention, those who did not receive anti-H pylori treatment were offered it. Gastric biopsies were obtained at baseline, and at 3, 6, and 12 years. A histopathology score was utilised to document changes in gastric lesions. Non-linear mixed models were used to estimate the cumulative effect of H pylori clearance on histopathology scores adjusted for follow up time, interventions, and confounders. RESULTS: Ninety seven per cent of subjects were H pylori positive at baseline, and 53% were positive at 12 years. Subjects accumulated 1703 person years free of infection. A multivariate model showed a significant regression in histopathology score as a function of the square of H pylori negative time. Subjects who were H pylori negative had 14.8% more regression and 13.7% less progression than patients who were positive at 12 years (p = 0.001). The rate of healing of gastric lesions occurred more rapidly as years free of infection accumulated, and was more pronounced in less advanced lesions. CONCLUSIONS: Preneoplastic gastric lesions regress at a rate equal to the square of time in patients rendered free of H pylori infection. Our findings suggest that patients with preneoplastic gastric lesions should be treated and cured of their H pylori infection.

Breast cancer: incidence, mortality, and early detection in Louisiana, 1988-1997.

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death among Louisiana women. The incidence data from Louisiana Tumor Registry were used to calculate breast cancer incidence rates, which were compared with the combined rates from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program. Breast cancer mortality rates for Louisiana were compared with the US death rates from the National Center for Health Statistics (NCHS). Our data revealed that Louisiana women were not at a higher risk for developing breast cancer than women in the SEER areas, but that mortality rates in Louisiana were not correspondingly low. Although the percentage of cases diagnosed at an early stage (in situ and localized) increased in Louisiana from 1988 through 1997, the average in Louisiana was still below the level for the SEER areas (65.9% and 71.6%) in 1993-1997. The rates of in situ breast cancer significantly increased (on average 5.3% for whites per year and 7.1% for blacks), and localized breast cancer also significantly increased (2.6% for whites and 2.5% for blacks), while the incidence of distant stage breast cancer significantly decreased (3.4% for whites and 2.0% for blacks). Compared with white women, black women still were less likely to be diagnosed with early stage breast cancer in 1993-1997 (56.4% and 68.9%). Women residing in the parishes with high percentages of persons in poverty were less likely to be diagnosed with early stage of disease.

KRAS mutations are not predictive for progression of preneoplastic gastric lesions.

Individuals with atrophic gastritis (n = 863) were recruited to participate in a chemoprevention trial in Nariño, Columbia. The volunteers were randomly assigned to intervention therapies, which included antibiotic treatment for Helicobacter pylori infection, and then daily dietary supplementation with antioxidant micronutrients in a 2(3) factorial design. Biopsies were obtained according to a specified protocol from designated areas in the stomach for each individual at baseline (before intervention therapy), at year 3, and at year 6. A systematic sample of 160 participants was selected from each of the eight treatment combinations, and the first exon of KRAS was examined for mutations. At year 3, the data indicated that individuals with KRAS mutations in their baseline premalignant stomach biopsies were 3.74 times as likely to progress to a higher premalignant stage than those who lacked baseline mutations (P = 0.04; C. Gong et al., Cancer Epidemiol. Biomark. Prevy. 8:167-171, 1999). However, after 6 years, baseline KRAS mutations failed to predict histological progression. Also, KRAS mutation in 72-month biopsies did not predict histological progression.

Morphometric evaluation of gastric antral atrophy: improvement after cure of Helicobacter pylori infection.

OBJECTIVE: Our purpose was to find out if morphometric techniques can document long term changes in gastric antral atrophy after curing Helicobacter pylori infection with or without dietary supplementation with antioxidant micronutrients. METHODS: Study subjects were 132 adult volunteers from a Colombian region with high gastric cancer rates. Participants were randomly assigned to ascorbic acid, beta-carotene, and anti-H. pylori treatment, following a factorial design. Gastric biopsies were obtained at baseline and after 72 months of intervention. Atrophy was evaluated by a standard visual analog scale and by morphometry. RESULTS: Statistically significant changes in antral atrophy were detected with morphometric techniques after intervention in subjects who received anti-H. pylori treatment. A nonsignificant trend was also observed with visual scores. This effect was greater among those who were free of infection at the end of the trial. After accounting for the effect of anti-H. pylori treatment, no significant effect was noted for dietary supplementation with ascorbic acid and/or beta-carotene. CONCLUSIONS: We conclude that gastric atrophy improves significantly after long term control of H. pylori infection. This effect can be demonstrated both by conventional histological grading and by morphometry.

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.

KRAS mutations predict progression of preneoplastic gastric lesions.

Eight hundred sixty-three subjects with atrophic gastritis were recruited to participate in an ongoing chemoprevention trial in Nariño, Colombia. The participants were randomly assigned to intervention therapies, which included treatment to eradicate Helicobacter pylori infection followed by daily dietary supplementation with antioxidant micronutrients in a 2 x 2 x 2 factorial design. A series of biopsies of gastric mucosa were obtained according to a specified protocol from designated locations in the stomach for each participant at baseline (before intervention therapy) and at year three. A systematic sample of 160 participants was selected from each of the eight treatment combinations. DNA was isolated from each of these biopsies (n = 320), and the first exon of KRAS was amplified using PCR. Mutations in the KRAS gene were detected using denaturing gradient gel electrophoresis and confirmed by sequence analysis. Of all baseline biopsies, 14.4% (23 of 160) contained KRAS mutations. Among those participants with atrophic gastritis without metaplasia, 19.4% (6 of 25) contained KRAS mutations, indicating that mutation of this important gene is likely an early event in the etiology of gastric carcinoma. An important association was found between the presence of KRAS mutations in baseline biopsies and the progression of preneoplastic lesions. Only 14.6% (20 of 137) of participants without baseline KRAS mutations progressed from atrophic gastritis to intestinal metaplasia or from small intestinal metaplasia to colonic metaplasia; however, 39.1% (9 of 23) with baseline KRAS mutations progressed to a more advanced lesion after 3 years [univariate odds ratio (OR), 3.76 (P = 0.05); multivariate OR adjusted for treatment, 3.74 (P = 0.04)]. In addition, the specificity of the KRAS mutation predicted progression. For those participants with G-->T transversions at position 1 of codon 12 (GGT-->TGT), 19.4% (5 of 17) progressed (univariate OR, 2.4); however, 60.0% (3 of 5) of participants with G-->A transitions at position 1 of codon 12 (GGT-->AGT) progressed (univariate OR, 8.7; P = 0.004 using chi2 test).

Cancer incidence in the industrial corridor: an update.

Because of the high density of industries along the Lower Mississippi River, there is a concern about adverse impact on health, including cancer, among residents in these parishes. This study provides an update of cancer incidence in the Industrial Corridor for the period 1989-93. Age-adjusted cancer incidence rates were calculated for the seven-parish study area from Baton Rouge down to, but not including, New Orleans. Rates were also computed for the entire state of Louisiana and for the combined Surveillance, Epidemiology and End Results (SEER) program. Cancer incidence rates for the Industrial Corridor are either similar to, or lower than, the combined SEER rates for most of the common cancers as well as for rare tumors. The only two exceptions are lung cancer in white males and kidney cancer in white females that are significantly elevated when compared to the SEER averages. Significantly lower rates are found among white males for cancers of kidney, brain, and nervous system, and melanoma; among black males, cancers of all sites combined, oral cavity, stomach, rectum, and prostate, Hodgkin's disease, and non-Hodgkin's lymphoma; among white females, cancers of all sites combined, cervix, uterine corpus, ovary, bladder, and melanoma; and among black females, cancers of all sites combined, oral cavity, lung, breast, ovary, and melanoma. The persistent excess of lung cancer has led to the development of a multi-agency project to evaluate the impact of potential environmental exposures, genetic susceptibility, and their interactions on lung cancer risk. The findings also confirm the urgent need to include and strengthen tobacco prevention and cessation programs in our cancer control activities.

Fatty foods and the risk of lung cancer: a case-control study from Uruguay.

To examine whether fatty-food consumption modifies lung-cancer risk, a case-control study involving 377 patients with lung cancer and 377 controls was conducted in Uruguay. The study was restricted to men. Dietary patterns were assessed in detail using a 64-item food-frequency questionnaire, which allowed the calculation of total energy intake. After adjustment for potential confounders (body-mass index, family history of lung cancer, total energy intake and tobacco smoking), an increase in risk for fatty-food consumption was observed. In particular, fried foods (OR, 1.54; 95% CI, 1.01-2.35), dairy products (OR, 2.85; 95% CI, 1.73-4.69) and desserts (OR, 2.52; 95% CI, 1.54-4.12) were associated with increases in lung-cancer risk and significant dose-response patterns. The association with dairy products was more evident for adenocarcinoma of the lung (OR, 4.18; 95% CI, 1.87-9.36), whereas increased risks for fried-meat and dessert consumption were observed in each cell type. The association with fried-meat consumption was more pronounced for current smokers and for heavy smokers, whereas dairy products and desserts were associated with risk both in current and in past smokers. In conclusion, fat-rich foods and sucrose-rich foods were positively associated with an increased risk of lung cancer. Although the relationship between fat consumption and lung cancer has been reported, the direct association of lung cancer with sucrose-rich foods should be further investigated.

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.

Is there a 'cancer corridor' in Louisiana?

Cancer mortality rates in South Louisiana are higher than the national averages, leading to the area's designation as a "cancer corridor". This study was conducted to assess whether incidence data substantiate the reputation derived from mortality statistics. Age-adjusted cancer incidence rates for 1983-1987 were calculated for South Louisiana as a whole, for five regional divisions of it, and for the combined nine areas of the Surveillance, Epidemiology, and End Results (SEER) program. Significantly lower (p < 0.0001) incidence rates were found in South Louisiana among white females, black males, and black females for cancers of all sites combined; among women of both races for cancer of the breast; among men of both races for cancers of the colon and prostate; and among whites of both sexes for melanoma and rectal cancer. South Louisiana incidence rates were significantly higher than the SEER rates only for lung and larynx cancers in white males. The excess of lung cancer was statistically significant in four out of five regions while the laryngeal cancer excess was significant only in the New Orleans area. The excessive mortality rates reported for South Louisiana are not the result of excessive incidence. These results indicate poorer cancer prognosis in this region, a phenomenon that deserves more scrutiny by the health profession.

Louisiana health and nutrition survey.

The objective of this project was to conduct a survey to estimate the current prevalence of high-risk dietary, occupational, and other lifestyle factors in subgroups of the Louisiana population by age, sex, race, and geographic region. A probability sample of adult Louisiana residents was selected using a 3-stage cluster design identical to that used in the Louisiana Behavioral Risk Factor Surveillance System. The reduced version of the Health Habits and History Questionnaire developed by Block et al at the National Cancer Institute was administered by telephone. The survey results are presented and discussed.

Family history of cancer and risk of lung cancer among lifetime nonsmoking women in the United States.

In a multicenter study of lung cancer in lifetime nonsmokers in the United States, 646 female lung cancer patients and 1,252 population controls were interviewed regarding history of cancer in their first-degree relatives. A 30% increased risk (95% confidence interval 0.9-1.8) was found for a history of respiratory tract cancer in parents or siblings after adjustment for exposure to environmental tobacco smoke (ETS) in adult life. Lung cancer, which represented approximately two thirds of the respiratory tract cancers, occurred more frequently in first-degree relatives of lung cancer patients than in comparable relatives of population controls (ETS-adjusted odds ratio = 1.29, 95% confidence interval 0.9-1.9). In particular, a significant threefold increased risk for lung cancer was associated with lung cancer diagnosed in mothers and sisters. The increased risk in relation to family history of lung cancer was observed among parents and siblings who were smokers as well as in those who were nonsmokers. The association with family history of lung cancer was strengthened when the analysis was restricted to adenocarcinoma of the lung (ETS-adjusted odds ratio = 1.50, 95% confidence interval 1.0-2.2). However, there was no association between family history of other cancers and risk of lung cancer in nonsmokers.

Antral atrophy, Helicobacter pylori colonization, and gastric pH.

The association between the topographic distribution of Helicobacter pylori colonization, inflammation and atrophy of the gastric mucosa, and fasting gastric pH was studied in a population with high prevalence of multifocal atrophic gastritis. Increasing atrophy of the antrum was associated with decreasing H pylori colonization of the antrum itself, but increasing colonization of the corpus. Advanced atrophy was associated with high fasting gastric pH. However, after therapeutic eradication of H pylori, inflammation subsided and gastric pH decreased indicating improved acid secretion despite persistent atrophy. The authors propose that antral atrophy fosters the colonization of oxyntic mucosa by H pylori, thus impairing acid secretion and causing hypochlorhydria that may further promote colonization of the oxyntic mucosa. Eradication of H pylori significantly improves hypochlorhydria. It may restore acid secretion in most patients, regardless of the presence of atrophy, which is an effect that may be of great benefit in halting the process of gastric carcinogenesis.

Do the nonsmoking daughters of smokers tend to marry smokers? Implications for epidemiological research on environmental tobacco smoke: the IARC collaborative study.

The IARC collaborative study on exposure to environmental tobacco smoke (ETS) involved collecting interview data and biochemical indicators of exposure from 1369 nonsmoking women in 13 centers in 10 countries. Information on childhood and adulthood exposure to other people's smoke and duration of this exposure from both parents and spouse was gathered at the interview. Of the 900 women whose husbands smoked (current or exsmokers), 71.3% had one or both parents who smoked (predominantly the father), whereas among the 277 women married to never-smokers, only 60.3% had at least one parent who smoked. The odds ratio for the daughter of a smoker to marry a smoker was, therefore, 1.64 (95% confidence interval = 1.24-2.17; P > 0.001), and there was an exposure-response relation between the number of years of childhood exposure to ETS from the parents and the likelihood of being married to a smoker. These results show that nonsmoking women married to smokers are more likely to have been exposed to tobacco pollution during their whole life. Because the duration of exposure is known to be important in the genesis of lung cancer, some of the excess risk of lung cancer in nonsmoking women married to smokers may be due exposure to ETS from parents during childhood.

Passive smoking and lung cancer.

Evidence that environmental tobacco smoke may be a risk factor for lung cancer among individuals who themselves have never smoked tobacco products has been the subject of expert review over the last decade by several United States and international agencies. The most recent comprehensive review, published in 1993 by the United States Environmental Protection Agency, concluded that environmental tobacco smoke is a Group A (known human) carcinogen. This report, coming in the midst of rapid social and political change in attitudes towards public policy implications for protecting human health, has been the subject of considerable discussion. Issues involved in these discussions, as well as more recently published studies on the topic, are reviewed with respect to current thinking about the risk of lung cancer in passive smokers, particularly women, who are lifetime never-smokers.