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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms by which exposure to cigarette smoke dramatically increase the incidence and severity of atherosclerosis and the incidence of lung cancer, chronic obstructive airways disease, and emphysema are incompletely understood. Epidemiologic evidence has suggested a modifying role for antioxidant micronutrients, including tocopherols and carotenoids, in these disease processes. It has been suggested that oxidants in cigarette smoke could be involved. We exposed freshly obtained human plasma to the gas phase of cigarette smoke to assess its effects on tocopherols, carotenoids, and retinol. Exposure to cigarette smoke led to the depletion of most of the lipophilic antioxidants in 20 mL human plasma. The order of disappearance was lycopene > alpha-tocopherol > trans-beta-carotene++ > (lutein + zeaxanthin) = cryptoxanthin > gamma-tocopherol = retinol. However, despite a substantial loss of alpha-tocopherol, there was very little peroxidative damage to lipids, and no detectable change in the content of polyunsaturated fatty acid-rich cholesterol esters. We conclude that a wide spectrum of lipophilic micronutrients undergo degradation when exposed to gas-phase cigarette smoke. The relevance of these in vitro findings to possible cigarette smoke-induced depletions of respiratory tract lipophilic antioxidants remains to be clarified.
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PMID:Destruction of tocopherols, carotenoids, and retinol in human plasma by cigarette smoke. 859 20

Plasma vitamins C, E, retinol and carotene were measured in 1971-1973 in 2,974 men working in Basel Switzerland. In 1990, the vital status of all participants was assessed. A total of 290 men had died from cancer during the 17 years of follow-up, including 87 with lung cancer, 30 with prostate cancer, 28 with stomach cancer and 22 with colon cancer. Overall mortality from cancer was associated with low mean plasma levels of carotene (adjusted for cholesterol) and of vitamin C. Lung and stomach cancers were associated with low mean plasma carotene level. After calculation of the relative risk, using the Cox model, with exclusion of mortality during the first 2 years of follow-up, simultaneously low levels of plasma carotene (below quartile I) and lipid-adjusted retinol were related to a significantly increased mortality risk for all cancers and for lung cancer. Simultaneously, low levels of plasma vitamin C and lipid-adjusted vitamin E also were associated with a significantly increased risk for lung cancer. Additionally, low vitamin E levels in smokers were related to an increased risk for prostate cancer. It is concluded that low plasma levels of the vitamins C, E, retinol and carotene are related to increased risk of subsequent overall and lung-cancer mortality and that low levels of vitamin E in smokers are related to an increased risk of prostate-cancer mortality.
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PMID:Prediction of male cancer mortality by plasma levels of interacting vitamins: 17-year follow-up of the prospective Basel study. 860 2

As part of the multicenter Carotene and Retinol Efficacy Trial (CARET) lung cancer prevention study, we investigated the associations of baseline demographic, health history, and nutritional intake information and the prerandomization serum concentrations of beta-carotene, retinol, retinyl palmitate, and alpha-tocopherol in a random subset of 1182 smokers and asbestos-exposed workers. Dietary intake was estimated via a self-administered food frequency questionnaire using the recently updated United States Department of Agriculture/National Cancer Institute database. In multiple regression analyses, supplemental vitamin use was the strongest predictor of each of the four analytes. There was a statistically significant inverse relationship between smoking and beta-carotene concentrations. Lower serum beta-carotene was associated with current smoking, higher daily cigarettes smoked, and more pack-years. Serum beta-carotene concentrations were higher with increasing years since stopping cigarette use, which suggests a biological mechanism for the lower serum concentration of beta-carotene in smokers. We found weak inverse associations between alcohol intake and the serum concentrations of both beta-carotene and retinol. As in previous reports, dietary intakes as measured by a food frequency questionnaire can only moderately predict serum concentrations of beta-carotene, retinol, retinyl palmitate, and alpha-tocopherol.
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PMID:The association between participant characteristics and serum concentrations of beta-carotene, retinol, retinyl palmitate, and alpha-tocopherol among participants in the Carotene and Retinol Efficacy Trial (CARET) for prevention of lung cancer. 889 93

Molecular epidemiology has made great progress in detecting and documenting carcinogenic exposures and host susceptibility factors, in an effort to explain interindividual variation in disease. Interindividual differences in cancer risk have been hypothesized to result from an array of both genetic and acquired factors including nutritional status. Elevated risk of lung cancer has been associated with polymorphisms of metabolic genes such as CYP1A1 and GSTM1. On the other hand, numerous studies have demonstrated that diets rich in fruits and vegetables are protective against cancer, and have correlated high levels of antioxidants in the blood with decreased risk. As a first step in identifying susceptible individuals, we have assessed the combined effect of genetic factors and nutritional status on DNA adducts in a population of healthy smokers. Plasma retinol, beta-carotene, alpha-tocopherol, and zeaxanthin were inversely correlated with DNA damage, especially in subjects lacking the "protective" GSTM1 gene. Research is ongoing using biomarkers to determine the effect of supplementation with antioxidants/vitamins on DNA damage, especially in population subsets with putative "at risk" genotypes. Information on mechanisms of interactions between exposure, micronutrients, and other susceptibility factors is important in the development of effective practical interventions.
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PMID:Application of molecular epidemiology to lung cancer chemoprevention. 902

Prior epidemiological evidence suggests that genes controlling the metabolism of carcinogens and antioxidant/nutritional status are associated with lung cancer risk, possibly through their ability to modulate DNA damage by carcinogens. We performed a cross-sectional analysis of 159 heavy smokers from a cohort of subjects enrolled in a smoking cessation program. A total of 159 blood samples were analyzed to determine the relative contributions of genetic polymorphisms [CYP1A1 MspI and exon 7 and glutathione S-transferase M1 (GSTM1)] and plasma micronutrients to polycyclic aromatic hydrocarbon-DNA (PAH-DNA) adduct levels. DNA damage in smokers was affected by genetic polymorphisms and nutritional status. Smokers with the CYP1A1 exon 7 valine polymorphism had significantly higher (2-fold, P < or = 0.03) levels of DNA damage than those without. In parallel models, PAH-DNA adducts were inversely associated with plasma levels of retinol (beta = -0.93, P = 0.01), beta-carotene (beta = -0.18, P = 0.09), and alpha-tocopherol (beta = -0.28, P = 0.21) in 159 subjects. The association between smoking-adjusted plasma beta-carotene levels and DNA damage was only significant in those subjects lacking the GSTM1 detoxification gene (beta = -0.30, P = 0.05, n = 75). There was a statistical interaction between beta-carotene and alpha-tocopherol; when beta-carotene was low, alpha-tocopherol had a significant protective effect (beta = -0.78, P = 0.04) on adducts, but not when beta-carotene was high (beta = -0.16, P = 0.57). Plasma alpha-tocopherol was significantly correlated with beta-carotene (r = 0.36, P = 0.0005) and less strongly with retinol (r = 0.20, P = 0.0005). These results suggest that several micronutrients may act in concert to protect against DNA damage and highlight the importance of assessing overall antioxidant status. In conclusion, a subset of smokers may be at increased risk of DNA damage and possibly lung cancer due to the combined effect of low plasma micronutrients and genetic susceptibility factors. The use of biological markers to assess efficacy of interventions and to study mechanisms of micronutrients is timely given the current debate regarding the use of chemopreventive agents in high risk populations.
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PMID:Contribution of genetic and nutritional factors to DNA damage in heavy smokers. 906 49

The association between serum beta-carotene or retinol concentration and level of ventilatory function was investigated in a population of asbestos-exposed men with a high rate of current and former cigarette smoking. The study population consisted of 816 subjects enrolled in the pilot component of the Carotene and Retinol Efficacy Trial (CARET), a placebo-controlled trial of supplemental beta-carotene and retinyl palmitate for the chemoprevention of lung cancer. Data available for analysis included baseline questionnaire, spirometry, chest X-ray, food frequency questionnaire, and serum beta-carotene and retinol concentrations. Serum beta-carotene concentration was associated with FEV1 (p < 0.05) and FVC (p < 0.05), with an approximately 100-ml increase over predicted values associated with raising the serum concentration from the 25th to the 75th percentile of the distribution in the study population (absolute difference = 155 ng/ml), even after adjustment for the confounding effects of asbestos exposure and cigarette smoking. Raising the serum retinol concentration from the 25th to the 75th percentile (absolute difference = 211 ng/ml) was associated with an approximately 70 ml increase in FVC (p < 0.05) over the predicted value. These results provide support for the hypothesis that beta-carotene and retinol have a protective effect on loss of ventilatory function.
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PMID:The protective effect of beta-carotene and retinol on ventilatory function in an asbestos-exposed cohort. 911 88

Vitamin A analogs (retinoids) suppress oral and lung carcinogenesis in animal models and prevent the development of second primary tumors in head, neck, and lung cancer patients. These effects result from changes in the expression of genes that regulate cell growth and differentiation. Retinoic acid receptors (RARs; -alpha, -beta, and -gamma) and retinoid X receptors (RXRs; -alpha, -beta, and, -gamma) are retinoid-activated transcription factors, which mediate effects of retinoids on gene expression. Therefore, alterations in receptor expression or function could interfere with the retinoid signaling pathway and thereby enhance cancer development. We found that the expression of RAR beta was suppressed in more than 50% of oral and lung premalignant lesions in individuals without cancer and in dysplastic lesions adjacent to cancer and in malignant oral and lung carcinomas. The expression of the other receptors was not different among normal, dysplastic, and malignant oral tissues. However, the expression of RAR gamma and RXR beta was somewhat decreased in lung cancers. These results show that RAR beta expression is lost at early stages of carcinogenesis in the aerodigestive tract and support the hypothesis that the loss of RAR beta expression may facilitate the development of some of these cancers.
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PMID:Roles of retinoids and their nuclear receptors in the development and prevention of upper aerodigestive tract cancers. 925 92

A case-control study on women was carried out in Barcelona, Spain, to investigate the relationship of lung cancer with the intake of vegetables, fruits and some foods of animal origin. The study included 103 cases and 206 controls matched by age and residence. Diet intake was assessed by means of a food frequency questionnaire. A reduction in risk, adjusted for smoking habit, was found for the intake of yellow/orange vegetables (mainly carrots) and tomatoes. The odds ratio (OR) and 95% confidence interval (CI) for the highest versus lowest tertile of intake were 0.37 (0.19-0.74) for yellow/orange vegetables and 0.45 (0.22-0.91) for tomatoes; both had a significant inverse trend. A tendency to a reduction in risk of lung cancer with increased intake was observed for all vegetables, leafy green vegetables, dark green vegetables and cruciferous, but these associations did not reach statistical significance. No association with lung cancer was found for the intake of fruits or foods of animal origin rich in retinol. Similar patterns were observed for women who never smoked and when the analysis was restricted to adenocarcinoma.
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PMID:Vegetable and fruit intake and the risk of lung cancer in women in Barcelona, Spain. 930 52

The Carotene and Retinol Efficacy Trial (CARET) was a double-blind, placebo-controlled trial of the daily administration of 25,000 IU vitamin A and 30 mg beta-carotene for the prevention of lung cancer. Of close to 18,500 participants, more than 4,000 were asbestos-exposed men recruited from shipyard and construction trades at five study centers in the United States. While the primary endpoint of the trial was the incidence of lung cancer, a number of questions about the natural history of asbestos-related disease will also be addressed. The mean age at entry into the trial was 57 years and the mean duration of follow-up on active intervention was 4 years. With the exception of 133 never-smoker pilot participants (3%), all subjects recruited were by intention current (38%) or ex-smokers (58%), with a mean cumulative smoking exposure at entry of 43 pack-years. Mean years from first asbestos exposure were 35, and mean duration of asbestos exposure in a high-risk trade was 19 years. The distribution of radiographic abnormalities was as follows: normal, 34%; parenchymal opacities (ILO profusion score > 1/0) alone, 18%; pleural thickening alone, 27%; both parenchymal opacities and pleural thickening, 21%. The CARET cohort, when compared to previously reported asbestos-exposed cohorts, is characterized by substantial asbestos exposure and high proportion of asbestos-related radiographic findings. The active intervention was halted in 1996, after a mean duration of 40 years. Passive follow-up of the cohort will continue until the year 2000.
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PMID:The CARET asbestos-exposed cohort: baseline characteristics and comparison to other asbestos-exposed cohorts. 935 12

Lower lobe origin and histologic diagnosis of adenocarcinoma have been described as useful parameters for attributing lung cancer to prior asbestos exposure. To assess whether these characteristics differed between asbestos-exposed individuals and smokers, we evaluated lobe of origin and histologic type of tumors in 78 asbestos-exposed and 214 nonexposed heavy smokers developing lung cancer during the Carotene and Retinol Efficacy Trial (CARET), a prospective cancer chemoprevention trial. Most tumors in both cohorts, regardless of radiographic fibrosis at baseline, originated in upper lobes, representing 67% in asbestos-exposed and 80% in smokers, respectively (adjusted OR for lower lobe = 1.41; 95% CI = 0.69-2.91). Adenocarcinoma represented 32% of lung tumors in the asbestos cohort, and 30% in the smoking cohort (adjusted OR = 0.78; 95% CI = 0.40-1.55), and was inversely associated with radiographic fibrosis (adjusted OR = 0.19; 95% CI = 0.06-0.62). We conclude that neither anatomic site nor histologic cell type of tumors distinguishes effectively between smoking and asbestos as causal factors in development of lung cancer.
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PMID:Lobe of origin and histologic type of lung cancer associated with asbestos exposure in the Carotene and Retinol Efficacy Trial (CARET). 935 13


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