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

The formation of carcinogen-DNA adducts within the respiratory epithelium is thought to be a critical factor in the induction of lung cancer from tobacco smoke. A reliable surrogate measure of carcinogen damage to the lung would be of great value in molecular epidemiological studies of cancer risk. The validity of measurements of DNA adducts formed from hydrophobic aromatic hydrocarbons in peripheral blood mononuclear cells (MNCs) was investigated by comparing the levels of aromatic DNA adducts detected in lung tissue from 31 lung cancer patients with those detected in MNCs from the same individuals using the 32P-postlabeling assay. The associations of smoking history and intake of dietary antioxidants with adduct levels also were assessed. Tissue-specific, as well as common DNA adducts were detected in lung and blood; total MNC adduct levels were highly correlated with total lung adducts. After smoking cessation, adduct levels appeared to decay in both tissues at similar rates. Multivariate analyses (Poisson regression modeling) indicated that dietary antioxidant intake (carotenoids, vitamin A, and retinol) modified the levels of aromatic DNA adducts in both the lungs and blood. Of all models tested, the optimal one for predicting lung adduct levels included the measure of blood MNC adduct levels only. Therefore, blood MNCs are a valid surrogate tissue for estimating the burden of DNA adducts in respiratory tissue in molecular epidemiological studies.
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PMID:Correlation of DNA adducts in blood mononuclear cells with tobacco carcinogen-induced damage in human lung. 758 29

Micronutrient deficiencies occur most commonly in poor countries and, therefore, are most likely to be associated with cancers common in these countries. Epidemiological studies are hampered by inaccurate measurement of micronutrient intake and by the correlations between intakes of many nutrients. The strongest evidence for a protective effect of micronutrients is for oesophageal cancer. The identity of the micronutrients is not certain, but may include retinol, riboflavin, ascorbic acid and Zn; alcohol, smoking and dietary nitrosamines increase the risk for oesophageal cancer. For stomach cancer there is good evidence that fruit and vegetables are protective. The protective effect of these foods might be largely due to ascorbic acid, but other nutrients and non-nutrients may also be important; the risk for stomach cancer is increased by salt, some types of preserved foods, and by infection of the stomach with the bacterium Helicobacter pylori. The risk for lung cancer appears to be reduced by a high intake of fruit and vegetables, but it is not clear which agents are responsible and the major cause of lung cancer is cigarette smoking. Diet is probably the major determinant of the risk for colo-rectal cancer; there is evidence that fruit and vegetables and fibre reduce risk and that meat and animal fat increase risk, but there is no convincing evidence that these relationships are mediated by micronutrients. The risk for cervical cancer is inversely related to fruit and vegetable consumption and, therefore, to consumption of carotenoids and ascorbic acid, but the major cause of this cancer is human papillomavirus and it is not yet clear whether the dietary associations indicate a true protective effect or whether they are due to confounding by other variables. The evidence that micronutrients are important in the aetiology of either breast cancer or prostate cancer is weak, but the possible roles of 1,25-dihydroxycholecalciferol and alpha-tocopherol in prostate cancer require further study.
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PMID:Micronutrients and cancer aetiology: the epidemiological evidence. 788 59

About 1% of the patients with oral cavity, larynx, and lung cancer get second primary malignant neoplasms every year. For laryngeal cancer the percentage exceeds 10. Second primary tumors in oral cavity, larynx, and lung cancer patients are also tobacco-related neoplasms. Smoking cessation by patients with oral cavity, larynx, and lung cancer may have significant influence on the prognosis. Vitamin A (retinol) and its analogues are promising for human cancer prevention.
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PMID:[Second primary malignant neoplasms in patients treated radically for carcinoma of oral cavity, larynx and lungs]. 809 Apr 86

Pilot studies are an essential component for major chemoprevention trials. Prior to initiating the multicenter Carotene and Retinol Efficacy Trial to assess the effectiveness of beta-carotene and retinol for preventing lung cancer, we conducted pilot studies in Seattle between 1985 and 1988 in two high risk populations: current and former heavy smokers and asbestos-exposed workers. The Asbestos Workers Pilot Study for the Carotene and Retinol Efficacy Trial demonstrated that recruitment of asbestos-exposed participants with relevant risk factors was feasible from identified sources. We documented negligible toxicity and high adherence with the protocol, schedule, and intervention. Results from the pilot led to extension of the placebo run-in period, changes in the eligibility criteria, improvements in recruitment strategies and scheduling, elimination of stratification by risk factors in randomization, modifications of study vitamin dosage and of side effects monitoring, and refinement of trial design parameters for Carotene and Retinol Efficacy Trial. The Smokers Pilot is reported in the accompanying article (G. E. Goodman et al., Cancer Epidemiol., Biomarkers & Prev., 2: 389-396, 1993).
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PMID:The Carotene and Retinol Efficacy Trial (CARET) to prevent lung cancer in high-risk populations: pilot study with asbestos-exposed workers. 834 62

In preparation for a phase IV lung cancer chemoprevention trial, we conducted a pilot trial of beta-carotene and retinol in high-risk smokers. Eligibility criteria were ages of 50-69 years, a smoking history of at least 20 pack-years, and either being a current smoker or having quit within the past 6 years. Participants were recruited by mailing an interest survey to 29,928 age-selected members of King County Medical Blue Shield. We randomized 1,029 women and men to one of four intervention arms: placebo, retinol, 25,000 international units/day; beta-carotene, 30 mg/day; or retinol plus beta-carotene. Participants were followed for side effects and adherence every 2 months either by a telephone call or a clinic visit. Blood was sampled for retinoid, carotenoid, and liver function analyses annually. beta-carotene and retinol were well tolerated during the follow-up period, which had a median of 1.5 years and a maximum of 3.3 years. Yellowing of the skin was seen in both beta-carotene arms. No differences were seen among arms or over time in incidence or severity of the other 15 monitored symptoms and signs or in serum liver function tests. Adherence was good: 83% of participants remained active on study at 1 year and 75% at 2 years. Serum beta-carotene increased from a prerandomization median concentration of 170 to 2100 ng/ml after 4 months of supplementation, and retinyl palmitate median levels more than tripled.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The Carotene and Retinol Efficacy Trial (CARET) to prevent lung cancer in high-risk populations: pilot study with cigarette smokers. 834 63

Chronic inhalation exposure to environmental carcinogens such as polycyclic aromatic hydrocarbons (PAHs), cigarette smoke, 4-aminobiphenyl (4-ABP), ethylene oxide, and styrene is associated with elevations in biomarkers such as DNA adducts, protein adducts, sister chromatid exchanges (SCEs), chromosomal aberrations, gene mutation, and/or oncogene activation. These biomarkers indicate an increased cancer risk for the exposed population, although quantitative estimates cannot be made with certainty. There is convincing epidemiological evidence that the antioxidant and free radical-scavenging vitamins C and E and beta-carotene (beta-C) protect against cancer of the lung and other epithelial tissues, with somewhat weaker evidence for retinol. Experimental studies demonstrate that these micronutrients are capable of blocking or reducing tumor formation caused by diverse carcinogens. A variety of mechanisms appear to be involved, including suppression of carcinogen activation, enhancement of carcinogen detoxification, induction of cellular differentiation, inhibition of mutagenesis, enhancement of immunologic function, and/or reduction of the formation of carcinogen-DNA adducts, SCEs, micronuclei, and other markers of genotoxic damage. Therefore, we have recently investigated the possible modifying effect of serum vitamins C and E, beta-C, and retinol on a number of such biomarkers in a case-control study of lung cancer, and in a cross-sectional study of heavy smokers. Preliminary results indicate an inhibitory effect of certain vitamins on DNA adduct formation. A significant number of human intervention trials are ongoing involving these vitamins. It appears that biomarkers can provide useful intermediate endpoints for assessment of both the mechanisms and the efficacy of chemopreventive agents.
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PMID:Molecular epidemiology of lung cancer and the modulation of markers of chronic carcinogen exposure by chemopreventive agents. 841 83

Because they may be used as a quantifiable estimate of the extent of recent DNA injury, micronuclei, extrachromosomal fragments of DNA, are among the most studied potential intermediate markers of cancer chemoprevention. Serial measurements of micronuclei frequency may be easily performed on scrapings from the oral cavity or on bronchial brushings. Assessment of micronuclei frequency and its response to chemopreventive agents has been incorporated into studies of upper aerodigestive tract and lung cancer chemoprevention. These studies have helped define the characteristics of micronuclei and have suggested a role for this test in future chemoprevention studies. Micronuclei frequency has been shown to be increased in the oral and bronchial mucosa of individuals with known carcinogen exposure and is higher at the site of the greatest carcinogen exposure, such as the site where tobacco quids are held, than in grossly normal-appearing mucosa. Treatment with chemopreventive agents leads to a reduction in micronuclei frequency. In oral leukoplakia studies, this effect followed treatment with beta-carotene, retinol, alpha-tocopherol, and 13-cis-retinoic acid. The multistep process of epithelial carcinogenesis results from DNA damage and specific genetic events. That micronuclei reflect ongoing DNA injury suggests the hypothesis that long term suppression of cellular genotoxicity, as reflected by a reduction in micronuclei frequency, ultimately leads to a reduction in cancer incidence.
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PMID:Micronuclei: a potential intermediate marker for chemoprevention of aerodigestive tract cancer. 841 1

Thyroxine (T4) and vitamin A are important regulators of normal epithelial differentiation and proliferation and might act in the promotion phase of carcinogenesis. Thyroid hormone and vitamin A metabolism are linked by a common plasma carrier protein, transthyretin (TTR). Polychlorinated biphenyls (PCBs) and related organochlorine compounds deplete vitamin A and thyroxine by interaction with TTR and alteration of their metabolism in hepatic and other organs. In the present report an outdoor airborne particulate matter (APM) extract was tested for both interaction with thyroid hormone and vitamin A metabolism, in order to address the question of whether APM has the potency to deplete vitamin A and thyroid hormones. Furthermore, studies were performed to characterize compounds present in APM that interact with TTR. A third aim was to compare the interaction of APM extracts with TTR and thyroxine-binding globulin (TBG), the major carrier protein for thyroxine in humans. Results showed that a single treatment of rats with an outdoor APM extract depleted plasma thyroxine and triiodothyronine levels and increased plasma retinol levels gradually over the time period studied, while liver retinol, lung retinol, and retinyl palmitate levels were depleted by 30-50%. As outdoor APM was able to inhibit T4-TTR binding in vitro, this suggests that the reduction in thyroxine levels in vivo is caused by the same phenomenon. Experiments showed that the neutral fraction of the APM extract accounted for most of the inhibitory activity on T4-TTR binding. Polycyclic aromatic hydrocarbons and nitrated derivatives are not likely to be responsible for the activity of the neutral fraction, because several representatives of these compounds showed no or very little interaction with TTR. Pentachlorophenol, a compound with known inhibitory activity on T4-TTR binding, was detected in the organic acid fraction of both a cigarette smoke sample and an outdoor APM sample. Finally, it was shown that several indoor and outdoor APM extracts only interact with TTR, but not with TBG. As APM has the potency to deplete lung vitamin A in vivo and vitamin A might have a protective effect in the process of lung carcinogenesis, APM might increase the susceptibility for the development of lung cancer.
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PMID:Effects on thyroid hormone metabolism and depletion of lung vitamin A in rats by airborne particulate matter. 847 82

Exposure to benzopyrene, an enzyme-inducing PAH carcinogen, promotes vitamin A depletion in exposed tissues. This effect is evident while on a vitamin A sufficient diet and without a decline in serum retinol. The finding of local tissue vitamin depletion without systemic depletion may have considerable implications in maintaining tissue health. While the described studies involved dietary exposure to benzopyrene, it is reasonable to extrapolate that inhalation exposure via cigarette smoke would have a similar effect in the lungs and perhaps stomach and bladder. Higher MFO enzyme activity in the lungs may have detrimental effects. Kellermann's early work identifying a higher incidence of lung cancer in those with genetically greater aryl hydrocarbon hydroxylase activity was interpreted as due to the greater formation of a reactive intermediate in the process of carcinogen metabolism. As an alternative hypothesis I suggest that those with higher enzyme inducibility may have greater carcinogen-induced vitamin A depletion. If poor tissue vitamin A nutriture potentiates the carcinogenicity of compounds such as benzopyrene, dietary or pharmacologic interventions which improve tissue nutriture could be important. The demonstrated effect of dietary beta-carotene on preventing carcinogen-induced tissue vitamin A depletion suggests one mechanism by which beta-carotene may be cancer protective. Further investigations are warranted, particularly with inhalation exposure to carcinogens and the effect of dietary beta-carotene on lung tissue nutriture.
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PMID:Carcinogen-induced tissue vitamin A depletion. Potential protective advantages of beta-carotene. 851 48

The hypotheses that the antioxidant vitamin E provides protection against lung cancer and that this hypothetical protection is modified by smoking status were investigated using two different study designs--a cohort study and a nested case-control study--among Finnish men aged 15 years and over. In the cohort study the association between vitamin E intake and lung cancer risk was studied among 5,254 individuals with 121 lung cancer cases that occurred during a 19-year follow-up, and in the nested case-control study the association between serum vitamin E level and lung cancer risk was studied using 144 lung cancer cases and 270 matched controls as a basis. There was a significant inverse association between vitamin E status and lung cancer occurrence among nonsmokers but not among smokers in both designs. The relative risk of lung cancer between the lowest and highest tertiles of vitamin E intake was 3.3 among nonsmokers and 0.8 among smokers. The corresponding results for serum vitamin E were 6.6 and 0.8, respectively. Nonsmokers with simultaneously low serum levels of vitamin E and other micronutrients (i.e., beta-carotene, retinol and selenium) had a 12-fold greater risk of lung cancer in comparison with men having more satisfactory levels. The corresponding number among smokers was three. The results suggest that vitamin E status is primarily associated with lung cancer risk among nonsmokers. Firm conclusions can, however, be drawn only on the basis of intervention trials.
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PMID:Vitamin E and smoking and the risk of lung cancer. 851 53


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