Volatile N-nitrosamine formation after intake of nitrate at the ADI level in combination with an amine-rich diet

Formation of nitrite from ingested nitrate can result in several adverse health effects and implies a genotoxic risk as a consequence of endogenous formation of carcinogenic N-nitroso compounds. We studied the formation of volatile N-nitrosamines after intake of nitrate at the acceptable daily intake (ADI) level in combination with a fish meal rich in amines as nitrosatable precursors. Twenty-five volunteers consumed this meal during 7 consecutive days; a diet low in nitrate was consumed during 1 week before and 1 week after the test week. Nitrate intake at the ADI level resulted in a significant rise in mean salivary nitrate and nitrite concentrations. Mean urinary nitrate excretion increased from 76 mg/24 hr in the first control week to 194 and 165 mg/24 hr in the test week, followed by a decline to 77 mg/24 hr in the second control week. The urine samples were analyzed for volatile N-nitrosamines, and both N-nitrosodimethylamine (NDMA) and N-nitrosopiperidine (NPIP) were detected in the samples. Mean urinary NDMA excretion significantly increased from 287 ng/24 hr in the control week to 871 and 640 ng/24 hr in the test week and declined to 383 ng/24 hr in the second control week. Excretion of NPIP was not directly related to the nitrate intake and composition of the diet. Nitrate excretion and NDMA excretion were significantly correlated, as well as salivary nitrate and nitrite concentration and NDMA excretion. We conclude that nitrate intake at the ADI level in combination with a fish meal containing nitrosatable precursors increases NDMA excretion in urine and thus demonstrates increased formation of carcinogenic N-nitrosamines.     

A parallel study of in vitro sensitivity to benzo[a]pyrene diol epoxide and bleomycin in lung carcinoma cases and controls

BACKGROUND: Because only a fraction of smokers develop neoplastic lesions, host factors may affect their susceptibility to the carcinogenic effects of tobacco smoke. Benzo[a]pyrene diol epoxide (BPDE) is the metabolic product of benzo[a]pyrene (B[a]P), a constituent of tobacco smoke. Therefore, BPDE sensitivity may shed some light on smoking-related carcinogenesis. METHODS: First, differential BPDE sensitivity was tested in five lymphoblastoid cell lines. Then sensitivity to BPDE and bleomycin (an excellent lung carcinoma risk predictor) was tested in parallel in the lymphocytes of 57 lung carcinoma cases and 82 controls. RESULTS: The optimal BPDE treatment duration was 24 hours. The xeroderma pigmentosum cell line was the most sensitive, followed by head and neck cancer, ataxia telangiectasia, and normal cells. The mean breaks per cell for cases and controls were 0.78 and 0.46, respectively (P < 0.0001). BPDE sensitivity was significantly associated with lung carcinoma, with an odds ratio (OR) of 7.26, compared with an OR of 4.56 for bleomycin sensitivity. There was also a dose-response correlation between the quartiles of BPDE-induced breaks and lung carcinoma risk, with ORs of 2.39, 3.12, and 15.03. It is noteworthy that individuals who were sensitive to both BPDE and bleomycin had a significantly increased OR of 38.36. CONCLUSIONS: BPDE sensitivity may be a biologic marker to identify individuals who are susceptible to the carcinogenic effects of tobacco smoke. BPDE and bleomycin sensitivity might represent different repair or sensitivity pathways; however, when these assays are used in parallel, they might refine our ability to identify high risk individuals.     

Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell carcinoma of the head and neck: a population-based case-referent study in Sweden

BACKGROUND: This case-referent study was conducted to elucidate the role of selected exogenous agents in the etiology of head and neck cancer. The factors studied were tobacco smoking, alcohol intake, the use of moist oral snuff, dietary factors, occupational exposures, and oral hygiene. In this first report, the authors discuss the impact of tobacco smoking, the use of oral snuff, and alcohol consumption. METHODS: The study base was approximately 2 million person-years at risk and consisted of Swedish males age 40-79 years living in 2 geographic regions during the years 1988-1990. A total of 605 cases were identified in the base, and 756 controls were selected by stratified random sampling from population registries covering the base. RESULTS: Among those who were tobacco smokers at the time of the study, the relative risk of head and neck cancer was 6.5% (95% confidence interval, 4.4-9.5%). After cessation of smoking, the risk gradually declined, and no excess risk was found after 20 years. The relative risk associated with alcohol consumption of 50 grams or more per day versus less than 10 grams per day was 5.5% (95% confidence interval, 3.1-9.6%). An almost multiplicative effect was found for tobacco smoking and alcohol consumption. CONCLUSIONS: Tobacco smoking and alcohol intake had a strong interactive effect on the risk of squamous cell carcinoma of the head and neck. Moderate alcohol intake (10-19 grams per day) had little or no effect among nonsmokers. No increased risk was found for the use of Swedish oral snuff.     

Dietary fats and lung cancer risk among women: the Missouri Women's Health Study (United States)

In a population-based case-control study of women in Missouri (United States), most of whom were smokers, we obtained information on adult diet to evaluate the effects of dietary fats in relation to lung cancer risk. All newly diagnosed, primary lung cancer cases among women 35 to 84 years of age reported to the Missouri Cancer Registry from 1 January 1993 to 31 January 1994 were invited to participate, as were population-based controls. The analysis focused on interviews obtained from 624 controls and 587 cases. In-person interviews were obtained from 99.0 percent of controls and 60.6 percent of cases. Age and energy-adjusted relative risks suggested a direct relation between risk of lung cancer and intake of dietary fats (e.g., total fat, saturated fat) and frequency of meat consumption. After adjusting for confounders, dietary fats were no longer associated with risk, but the adverse effect of frequent consumption of meat persisted. Risk was elevated about 90 percent (95 percent confidence interval = 1.2-3.0) among women in the highest quintile of red meat intake compared with those in the lowest quintile. Risk estimates associated with red meat consumption, however, were dependent on interview status; the effect was restricted to cases whose dietary information was provided by proxy. In summary, after adjusting for potential confounders and removing data obtained from proxy respondents, dietary fats and consumption of red meat were not associated with lung cancer risk among women in Missouri.     

Detection of microbial pathogens in shellfish with multiplex PCR

This study investigated the effect of drinking tea or coffee on the lung cancer risk of male cigarette smokers in a case-control in Uruguay. Four hundred and twenty-seven lung cancer cases were frequency matched on age and residence with 428 hospitalized controls suffering from conditions unrelated to tobacco smoking and diet. Whereas coffee drinking had no effect on the lung cancer risk of the cigarette-smoking men in this study, black tea consumption decreased this risk. Heavy drinkers of tea (two or more cups of tea per day) were associated with a reduced risk of 0.34 (95% CI 0.14-0.84). This protective effect was more evident among Kreyberg I tumors (squamous cell and small cell) and among light smokers. Possible sources of bias and mechanisms of action are discussed.     

Clinical evaluation of hepatic bruit audible in patients with alcoholic hepatitis]

Human exposure to methylating agents appears to be widespread, as indicated by the frequent occurrence of methylated DNA adducts in human DNA. The high incidence of methylated DNA adducts even in humans thought not to have suffered extensive exposure to environmental methylating agents implies that chemicals of endogenous origin, probably N-nitroso compounds such as the strongly carcinogenic N-nitrosodimethylamine (NDMA), may be primarily responsible for their formation and raises the question of the carcinogenic risks associated with such exposure. In addition to accumulation of DNA damage, other factors (such as induced cell proliferation) appear to be important in determining the probability of induction of mutation or cancer by NDMA, implying that high to low dose risk extrapolations should not be based on the assumption of dose- or even adduct-linearity. Comparative studies of the accumulation and repair of methylated adducts in humans and animals treated with methylating cytostatic drugs do not reveal significant species differences. Based on this and the dosimetry of adduct accumulation in rats chronically exposed to very low doses of NDMA, it is suggested that the exposure needed to account for the levels of adducts found in human DNA may be of the order of hundreds of micrograms NDMA (or equivalent) per day, a level of exposure which may well represent a significant carcinogenic hazard for man.     

Investigation of the neurogenic bladder

Cancer has been associated to well-defined risk factors. Nutritional factors and tobacco are the most important causes of cancer deaths. Prevention should be based on health education. Beikost guidelines should be the early step to implement a healthy diet. American Cancer Society, US Department of Health and Human Services, and the National Academy of Sciences recommendations are analyzed. Recommendations include maintain a desirable body weight, eat a varied diet, include a variety of both vegetable and fruits, eat more high fiber foods, cutdown on total fat intake, limit consumption of alcoholic beverages, salt-cured, smoked and nitrite-cured foods. Suggestions relate to caution with food additives, increase vitamin E intake, proper selenium intake, limit artificial sweeteners, reduce coffee and cholesterol consumption, avoid cooking at high temperatures. Local diets fulfil most of the recommendations. Tobacco consume carries a higher risk of cancer arising from different locations. Pre- and postnatal exposure to tobacco smoke is harmful to health. Prevention requires the combined action of parents, teachers, health professionals, civic associations and governmental institutions.     

Protein kinases A and C phosphorylate purified Ca2+-ATPase from rat cortex, cerebellum and hippocampus

Previous knowledge on risk factors for oral, pharyngeal, laryngeal, and esophageal cancer has been based mainly on case-control studies. In the present study, the impact of alcohol consumption, tobacco smoking, and dietary factors on upper aerogastric tract cancer risk was studied in a cohort of 10,960 Norwegian men followed from 1968 through 1992, in which period a total of 71 upper aerogastric tract cancers occurred. The relative risk (RR) of cancer was 3.9 (95 percent confidence interval [CI] = 2.1-7.1) for the highest consumption group of alcohol and 4.7 (CI = 1.7-13.2) for the highest smoking level, compared with the respective reference groups. Among the dietary items, high consumption of oranges was associated with reduced cancer risk (RR = 0.5, CI = 0.3-1.0), as was high consumption of bread (RR = 0.2, CI = 0.1-0.5). Frequent consumption of beef and bacon increased relative cancer risk bordering on significance. The present results are largely in accordance with previous studies. The decreased risk associated with a high intake of bread deserves further investigation.     

Tobacco and tobacco smoke

Epidemiologic studies have demonstrated a causal relation between smoking of cigarettes and cancer of the lung in man. Women smokers, cigar, and pipe smokers also face an increased risk for lung cancer. Prospective and retrospective studies have found a correlation between smoking of cigarettes, cigars, and pipes and cancer of the oral cavity, larynx, and esophagus and for cigarette smokers increased risks to develop cancer of the pancreas, kidney, and urinary bladder. Dose responses have been established between number of cigarettes smoked and cancer of the respiratory and upper digestive tract. Tobacco chewers face an increased risk for cancer of the mouth and esophagus. Tobacco smoke has induced tumors of the lung in the dogs and of the larynx of hamsters. The particulate matter of the smoke is carcinogenic to the skin of mice and rabbits, and the bronchi and connective tissue of rats. In tobacco smoke were identified tumor initiators, tumor promoters, cocarcinogens and organ specific carcinogens. Chewing tobacco is a tumor promoting agent and contains traces of tobacco specific and carcinogenic nitrosamines. Ten to 15 yr after giving up smoking the ex-smoker faces the same low risk to develop cancer of the upper digestive tract, the lung, the pancreas, and the urinary tract as the nonsmoker. It should be our goal, therefore, to prevent young people from starting the smoking habit and to convince the smoker to quit smoking. So far, we can report no success in terms of decreasing smoking habits among younger people. On the other hand, we can take satisfaction from the fact that antismoking propaganda has had an effect on college educated males, that among the population as a whole, there is a considerable number of exsmokers; that smoking cessation clinics do prove cost effective and if they were to become part of every health care center, they could help a large number of heavy smokers who cannot seem to stop smoking on their own. We can also report that there has been a significant reduction in the tar yield of American cigarettes, a reduction which we hope will continue; that the tumorigenic activity of tobacco as measured in animal studies, has decreased; and that as a consequence of the above, the risk of lung cancer and other tobacco-related cancers among smokers of these cigarettes is lower than in years past. It is unlikely that man will ever be able to inhale smoke components as harmless as unpolluted air, but as long as we have a society which accepts this habit and as long as people find satisfaction in smoking, we must work towards the day when tobacco-related cancers and other diseases will be reduced to a minimum. With the world wide coperation of the scientific community, the Departments of Agriculture, and the tobacco industry, it is our hope that this goal will be achieved.     

Cellular interactions in the thymus regulate the protein kinase C signaling pathway

Lung cancers occur more commonly in the upper lobes than in the lower lobes, but its pathophysiologic basis is not well understood. Because numerous studies have reported a consistent inverse relationship between lung cancer risk and intake of certain vegetables and fruits, we hypothesized that the balance between diet-derived protective substances delivered via the circulation and cigarette-derived carcinogenic substances delivered via the airways would be less favorable in the upper lobes compared with the lower lobes, hence accounting for the upper lobe predominance of tumors among smokers. Thus, we examined the association between diet and tumor location in 328 patients with lung cancer. The ratio of upper to lower lobe tumors was 2.5:1.0. In univariate analysis, age, height, weight, sex, race, family history of cancer, education level, tumor histology, calories consumed per day, and intake of animal fat did not differ significantly between patients with upper versus lower lobe tumors. Predictors of tumor location in univariate analysis were family history of lung cancer; smoking history; history of asbestos exposure; and intakes of yellow-orange vegetables, alpha-carotene, beta-carotene, and vitamins A, C, and E. In multivariable logistic regression analysis, the independent predictors of upper lobe tumor location were family history of lung cancer (p = 0.03), history of asbestos exposure (p = 0.02), less intake of yellow-orange vegetables (p < 0.04), and less intake of vitamin E (p = 0.05). Our results show a strong inverse association between upper lobe location of lung cancer and intake of yellow-orange vegetables and vitamin E.     

p34cdc2 expression and meiotic competence in growing goat oocytes

Proper control of environmental factors can be crucial to the identification of genes that influence susceptibility to a complex trait, especially for a trait such as lung cancer, for which the environmental factor (smoking) accounts for a significant etiologic fraction of the disease. An earlier segregation analysis of 337 Louisiana families, which incorporated direct measure of tobacco consumption, provided evidence for autosomal codominant inheritance of a major gene that influenced age at onset of lung cancer. Subsequent analyses were performed in which the families were stratified into two subsets based on birth cohort of the proband; results suggested the presence of heterogeneity that were postulated to reflect the influence of cohort trends in tobacco consumption. To evaluate this hypothesis further, we simulated a population of three-generation pedigrees in which an autosomal dominant mode of susceptibility to lung cancer was transmitted, but tobacco use varied across generations corresponding to published trends in smoking. A total of 200,000 individuals in families of various sizes, ages, and cigarette smoking habits were simulated from 1900 to 1980. From this population, 324 families (2,405 individuals) with 380 cases of lung cancer were ascertained through 328 lung cancer probands. Complex segregation analysis was performed using the REGTL program of S.A.G.E. in which pack-years of tobacco exposure were incorporated directly into the likelihood calculations. Although the no major gene, environmental, and Mendelian recessive hypotheses were rejected, both dominant and codominant transmission provided a good fit to the data. Thus in a population of simulated families with autosomal dominant susceptibility to lung cancer, intergenerational differences in tobacco consumption led to the detection of autosomal codominant transmission as an acceptable hypothesis. These results underscore the potential danger of segregation analysis of complex traits in which exposure to known environmental influences may differ across generations.     

Characteristic magnetic resonance imaging entheseal changes of knee synovitis in spondylarthropathy

Although studies generally support a positive association between alcohol consumption and lung-cancer risk, the relationship between specific alcoholic beverages and lung-cancer risk has been inconsistent. We examined recent and past alcoholic beverage intake among 261 incident cases and 615 population controls enrolled in a lung-cancer case-control study of African Americans and Caucasians in Los Angeles County between 1991 and 1994. An in-person interview elicited information about past alcohol intake from ages 30 to 40 y, smoking, other lung-cancer risk factors, as well as recent intake of alcohol, and recent dietary intake. An association was observed between recent hard-liquor consumption and lung-cancer risk. The odds ratio (OR) for 1 or more drinks (1.5 oz or 0.051 mL) per day of hard liquor compared with infrequent liquor drinking (0-3 drinks per month), adjusted for smoking, the matching factors, saturated fat and other alcoholic beverages was 1.87 [95% confidence interval (CI) = 1.02-3.42]. No appreciable association was observed for total alcohol, whereas small inverse associations were observed for beer and wine, although confidence intervals were wide. An elevated lung-cancer risk was also observed for past liquor consumption (between ages 30 and 40 y). The adjusted OR for 1 or more drinks per day of liquor compared with infrequent drinkers was 1.83 (95% CI = 1. 06-3.15). Confounding of the association between alcohol and lung cancer by smoking was apparent. Although we devoted considerable efforts to adjusting for smoking in our analyses, residual confounding is still possible because smoking and alcohol are closely associated. In addition, case-control studies including this study should be viewed with caution because of possible selection bias. An increased risk of lung cancer might occur with moderate drinking of hard liquor but confirmation is required in larger studies.     

Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance

BACKGROUND: Experimental and epidemiologic investigations suggest that alpha-tocopherol (the most prevalent chemical form of vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and beta-carotene (a plant pigment and major precursor of vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received beta-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of beta-carotene and vitamin A. PURPOSE: We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum vitamin status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations. METHODS: A total of 29,133 men aged 50-69 years who smoked five or more cigarettes daily were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), alpha-tocopherol and beta-carotene, or a placebo daily for 5-8 years (median, 6.1 years). Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry, along with measurements of serum levels of alpha-tocopherol and beta-carotene. Incident cases of lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models. All P values were derived from two-sided statistical tests. RESULTS: No overall effect was observed for lung cancer from alpha-tocopherol supplementation (relative risk [RR] = 0.99; 95% confidence interval [CI] = 0.87-1.13; P = .86, logrank test). beta-Carotene supplementation was associated with increased lung cancer risk (RR = 1.16; 95% CI = 1.02-1.33; P = .02, logrank test). The beta-carotene effect appeared stronger, but not substantially different, in participants who smoked at least 20 cigarettes daily (RR = 1.25; 95% CI = 1.07-1.46) compared with those who smoked five to 19 cigarettes daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol intake (> or = 11 g of ethanol/day [just under one drink per day]; RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake (RR = 1.03; 95% CI = 0.85-1.24). CONCLUSIONS: Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke. beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect may be associated with heavier smoking and higher alcohol intake. IMPLICATIONS: While the most direct way to reduce lung cancer risk is not to smoke tobacco, smokers should avoid high-dose beta-carotene supplementation.     

Differential response to lithium and carbamazepine in the prophylaxis of bipolar disorder

The relation between selected indicator foods, alcohol and coffee intake, and the risk of pancreatic cancer was evaluated in a case-control study conducted between 1983 and 1992 in northern Italy on 362 patients with histologically confirmed, incident cancers of the pancreas, and 1,552 controls in hospital for acute, non-neoplastic diseases. Odds ratios (ORs) for subsequent tertiles of intake were computed after allowance for sociodemographic factors and tobacco smoking. Pancreatic cancer risk was directly associated with consumption of meat (OR for the highest frequency tertile = 1.43), liver (OR = 1.43) and ham and sausages (OR = 1.64), and inversely with consumption of fresh fruit (OR = 0.59), fish (OR = 0.65) and olive oil (OR = 0.58). No appreciable association was found with coffee (OR = 1.21) and alcohol consumption (OR = 1.20). A summary score was derived by summing the six related food items; compared to the lowest level, the OR was 2.7 for the highest quintile, and the population attributable risk was 36% (95% confidence interval, 15-57%), indicating the scope of diet for the prevention of this common neoplasm in the Italian population.     

Cancers related to tobacco smoking

Tobacco smoking is the major cause of lung cancer. Cigarette smokers have a risk of lung cancer 10 to 15 times greater than nonsmokers. Tobacco and alcohol are the main risk factors for cancers of oral cavity, larynx, pharynx and oesophagus (cancers of the upper respiratory and upper digestive tract) and the effects of tobacco and alcohol are multiplicative. For these cancers, the risk associated with tobacco was about 2 to 4 among people who drink little or no alcohol. Risks of lung cancer and of cancers of the upper respiratory and upper digestive tract increase with an increasing number of cigarettes smoked per day and duration of smoking. Tobacco is also a risk factor for bladder cancer. Cigarette smoking is a possible contributory factor in the development of kidney, pancreatic and cervical cancers. Among males, lung cancer mortality increased regularly over time and today, lung cancer is the leading cause of death and illness from cancer. Substantial reductions in the number of deaths from tobacco-related cancers could be achieved if a large proportion of smokers stopped smoking.     

Dietary factors and lung cancer among men in west Sweden

BACKGROUND: Previous studies have reported an association between tea drinking and lung cancer. In view of these data, the relationship between tea drinking as well as other dietary factors and lung cancer was investigated in a case-control study in the west of Sweden. METHODS: Patients with suspected lung cancer were collected from pulmonary units at central hospitals in the area investigated, and population controls were matched for age. The material reported here comprises 308 male cases with a confirmed diagnosis of lung cancer and 504 controls. The participants were interviewed by specially trained nurses, using a questionnaire to assess smoking, dietary habits, occupational exposures and conditions in the residential area (local air pollution). This paper reports the results from dietary factors studied with a food frequency technique. RESULTS: The results demonstrated a strong protective effect of vegetables (odds ratio [OR] = 0.69, 95% confidence interval [CI]: 0.46-1.05, and OR = 0.37, 95% CI: 0.23-0.61 for intermediate and high consumption classes respectively). A low OR was consistent for all histological types of lung cancer. High consumption of fruits did not show any similar protective effect. Drinking milk was associated with a dose-response related risk increase after adjustment for smoking and vegetable consumption (P for trend = 0.07). Odds ratio was 1.73, 95% CI: 1.00-3.01 for high consumption of milk. CONCLUSIONS: High intake of vegetables had a strong protective effect among males. Diet is thus a potential confounding factor in studies on lung cancer and environmental factors and should thus be taken into consideration in the planning of such studies.     

Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to several ecological receptor groups: a short review

The objective of this study was to examine the risks for lung cancer associated with lifestyle characteristics of smoking in a developing country where lung cancer is the first cause of mortality by cancer in men, tobacco propaganda is freely allowed, and there are no restrictions operating for smoking. The design was a case-control and hospital-based study. Two hundred men with lung cancer and 397 hospital controls were interviewed. Odds ratio (OR) for current smokers was 8.5, whereas former smokers displayed an OR of 5.3. The risk increased with duration of smoking and with the number of cigarettes smoked per day. The attributable risk for smoking was 85%. Smokers of black tobacco and more than 24 cigarettes/day showed a risk of 12.9 regarding non-smokers, and of 15.5 for 40 or more years duration of smoking. The proportion of cases diagnosed as adenocarcinoma was higher than the proportion of squamous cell carcinoma.     

Serum fatty acids and the risk of fatal cancer. MRFIT Research Group. Multiple Risk Factor Intervention Trial

To examine the relation between serum fatty acids and cancer, the authors conducted a nested case-control study of 108 middle-aged men who died of cancer and 215 men without cancer, who were enrolled in the Multiple Risk Factor Intervention Trial (MRFIT) between 1973 and 1976. Control subjects were matched to case subjects on age, smoking status, treatment assignment, date of randomization, and clinical center. After confirming the stability of the stored serum samples, the authors measured serum fatty acid levels by gas-liquid chromatography and analyzed their association with cancer. In stepwise logistic regression analyses that controlled for the MRFIT selection criteria variables and for alcohol consumption, no fatty acid was significantly associated with overall risk of cancer death (all p > 0.05). Serum levels of phospholipid dihomogammalinolenic acid (20:3), an essential fatty acid, were inversely associated with the risk of dying from lung cancer; a standard deviation increase was associated with a 32% decrease in risk (p = 0.05). Dietary cholesterol intake was associated with the risk of nonlung, non-digestive tract cancers; a standard deviation increase (331 mg/day) was associated with a 75% increase in risk (p = 0.02). The authors found no evidence to suggest that increased dietary intake or serum levels of polyunsaturated fatty acids were associated with an increased risk of fatal cancer among middle-aged men at high risk for coronary heart disease. The clinical significance of the inverse association between dihomogammalinolenic acid and lung cancer death is uncertain and requires confirmation.     

Genetic polymorphisms of drug-metabolizing enzymes and susceptibility to lung cancer--relevance to smoking

Lung cancer has been associated with smoking and many carcinogenic compounds are thought to contribute to the origin of lung cancer. Most of these carcinogens exert their carcinogenicity after conversion to more potent forms through reactions mediated by drug-metabolizing enzymes, such as cytochrome P450s (CYPs). Carcinogens in the human body are then detoxified by enzymes such as glutathione S-transferase (GST) and excreted. The genetic differences, or polymorphisms, of these enzymes may affect genetically-determined susceptibility to lung cancer. Recently, a variety of polymorphisms have been found for drug-metabolizing enzymes in humans, such as CYP2E1, CYP1A1, CYP2D6, and GST. These polymorphisms have been related to susceptibility to lung cancer by some researchers. Their relevance with the dose of tobacco smoke has also been investigated.     

Cytological study of exfoliated buccal mucosa cells of tribes in Orissa State (India) with high risk for oral cancer

Buccal mucosa scrapings from 50 individuals belonging to tribes of Koraput district in Orissa State (India), were smeared and fixed. The cells were stained adopting Feulgen technique. All the tribes are active tobacco and alcohol users. The individuals were asked about their age, sex, food habit, tobacco and alcohol consumption habit, period of consumption and daily consumption quantity. Micronuclei were scored from the smeared cells as increase in micronucleus frequency in buccal mucosa cells of tobacco and alcohol users indicates a high risk group for oral cancer. At least 1000 cells per sample were screened. The frequency of micronucleated cells is found to be higher (7.37%) in case of male individuals than female individuals (5.90%). Individuals of both sexes of age group (50-65) years show higher frequency of micronucleus. Tobacco smokers with Pika habit show higher frequency of micronucleus (7.06%) than tobacco chewers with Dungia habit (6.33%). Such increase in micronucleus frequency in buccal mucosa cells indicates that the tribes are high risk of oral cancer.