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

Recent prospective studies have suggested that insulin-like growth factor (IGF)-I levels are related to risk of some epithelial cancers. We previously reported in a case-control study a significant association between IGF-I level and lung cancer risk, with a 2-fold increased risk in the highest quartile. We now report the results of a lung cancer case-control study nested in the placebo arm of the beta-Carotene and Retinol Efficacy Trial in heavy smokers. We identified 159 cases for whom sera had been collected at least 3 years before diagnosis and for whom 2 suitable controls/case (final number, 297) could be matched from the same study arm on age (within 5-year intervals), sex, ethnicity, year of enrollment into the beta-Carotene and Retinol Efficacy Trial, year of blood draw, and exposure category (smoking or asbestos). The cases were significantly heavier smokers than the controls (mean pack-years, 58.7 and 45.9, respectively; P < 0.001). An inverse relationship between IGF-I level and age was evident only for former smokers, and not for those who were current smokers at the time of blood draw. Both IGF-I and IGF-binding protein (IGFBP)-3 levels were higher in cases than in controls, but none of the differences achieved statistical significance. The odds ratios for IGF-I were around unity, except for subsets of heaviest smokers and those who had quit smoking for the longest period of time, in whom there were elevated risks in the second to fourth quartiles of IGF-I relative to the first quartile (odds ratios, 2.21-2.91), although again, none achieved statistical significance. For younger subjects, IGF-I was inversely associated with lung cancer risk in the models that also controlled for IGFBP-3. Elevated risks for lung cancer were noted in the highest quartile of IGFBP-3 level, and these tended to be higher in current smokers and more recent quitters. These results do not support the conclusions of our prior case-control study. It is possible that current smoking or recent cessation may exert a suppressive effect on IGF-I levels (notably in younger subjects with higher baseline levels) that may obscure a relatively modest association between IGF-I level and lung cancer risk. On the other hand, risks associated with elevated IGFBP-3 level tended to be higher in current smokers and more recent quitters. This trend toward a positive association with IGFBP-3 level is unexpected and requires further investigation. Finally, from these data, we cannot exclude the possibility that risk of lung cancer in nonsmokers may be related to IGF-I levels.
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PMID:Serum insulin-like growth factor (IGF) and IGF-binding protein levels and risk of lung cancer: a case-control study nested in the beta-Carotene and Retinol Efficacy Trial Cohort. 1243 20

The Carotene and Retinol Efficacy Trial (CARET) was a large, multicenter randomized chemoprevention trial designed to test a combined lung cancer prevention agent in heavy smokers and workers exposed to asbestos. In January 1996, the CARET Steering Committee decided to stop the intervention due to an adverse effect. This paper describes the decision process used to apply the stopping rules and the activities engaged in by CARET participants and staff to implement the decision. The most important activity was to draft and mail a letter to the participants informing them of the disappointing CARET results and asking them to stop taking the study vitamins and to return any unused study vitamins. The steering committee, with the support of the National Cancer Institute, planned to follow participants for disease endpoints and smoking behavior for 5 years. These activities led to smooth closure of active intervention and maintained high retention rates during the transition.
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PMID:Stopping the active intervention: CARET. 1255 41

The beneficial and adverse effects of some chemopreventive agents, such as Vitamins A, C, E, beta-carotene, indole-3-carbinol, capsaicin, garlic, and aloe are reviewed. Two large randomized trials with a lung cancer endpoint, the Alpha-Tocopherol, Beta-Carotene (ATBC) Prevention Study and the Beta-Carotene and Retinol Efficacy Trial (CARET), suggested that antioxidants might be harmful in smokers. However, the results of the Linxian study and of the ATBC or the CARET studies were significantly different in this respect, and therefore, the relationship between antioxidant and carcinogenesis remains open to debate. Indole-3-carbinol has cancer promoting activities in the colon, thyroid, pancreas, and liver, whereas capsaicin alters the metabolism of chemical carcinogens and may promote carcinogenesis at high doses. Organosulfur compounds and selenium from garlic have no or a little enhancing effect on cancer promotion stage. Information upon chemopreventive mechanisms that inhibit carcinogenesis is imperfect, although the causes and natures of certain human cancers are known. Therefore, definitive preventive guidelines should be carefully offered for various types of tumors, which properly consider ethnic variations, and the efficacies and the safety of chemopreventive agents.
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PMID:Beneficial and adverse effects of chemopreventive agents. 1262 24

Despite the unexpected results from the beta-Carotene and Retinol Efficacy Trial (CARET) and similar supplementation trials showing that supplementation with beta-carotene increased, rather than decreased, lung cancer incidence, considerable interest remains in investigating how other compounds in fruits and vegetables may affect lung cancer risk. We used data from 14,120 CARET participants who completed food frequency questionnaires to examine associations of diet with lung cancer risk. After 12 years of follow-up (1989-2001), 742 participants developed lung cancer. We used Cox proportional hazards models to estimate multivariate relative risks (RRs) and 95% confidence intervals (CIs). Analyses were controlled for smoking, asbestos exposure, and other covariates. Analyses of specific botanical groups were also controlled for total fruit and vegetable intake. All models were stratified by CARET treatment arm, and all statistical tests were two-sided. Statistically significant associations of fruit and vegetable intake with lower lung cancer risk were restricted to the CARET placebo arm. The RR for highest versus lowest quintile of total fruit consumption in the placebo arm was 0.56 (95% CI, 0.39-0.81) with a two-sided P for trend = 0.003. Two specific botanical groups were associated with reduced risk of lung cancer. Compared with the lowest quintile of rosaceae fruit consumption, placebo participants in the top quintile had a RR of 0.63 (95% CI, 0.42-0.94; P for trend = 0.02); for cruciferae vegetables, the RR was 0.68 (95% CI, 0.45-1.04; P for trend = 0.01). We did not observe any statistically significant associations of fruit and vegetable intake with lung cancer risk among participants randomized to receive the CARET supplements (30 mg of beta-carotene and 25,000 IU of retinyl palmitate). This report provides evidence that plant foods have an important preventive influence in a population at high risk for lung cancer. However, persons who use beta-carotene supplements do not benefit from the protective compounds in plant foods.
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PMID:Fruits and vegetables are associated with lower lung cancer risk only in the placebo arm of the beta-carotene and retinol efficacy trial (CARET). 1506 39

beta-Carotene and Retinol Efficacy Trial is a nationwide chemoprevention trial that recruited 18,314 high-risk individuals to test the effect of supplemental beta-carotene and retinol on lung cancer incidence. In this report, we conducted a prospective nested case-control study of the association between serum carotenoids, retinoids, and tocopherols on both lung and prostate cancer incidence. Prerandomization serum samples were selected from 278 lung cancer cases and 205 prostate cancer cases, and 483 controls matched by high-risk population, study center location, age, sex (lung cancer only), smoking status, and year of randomization. Carotenoids, retinoids, and tocopherols were analyzed by high-performance liquid chromatography. Endpoints were confirmed by pathology review (lung cancer) or review of the pathology report (prostate cancer). In the control-only population, there was a significant association between tobacco use and serum micronutrient concentration. Current smokers compared with former smokers had lower mean levels of all of the micronutrients tested with zeaxanthin, beta-cryptoxanthin, alpha-carotene, alpha-tocopherol, retinol, and retinyl palmitate reaching statistical significance at P = 0.05. In the overall population, the mean serum concentrations of all of the micronutrients except gamma-tocopherol were lower for lung cancer cases than controls. Statistically significant trends across quartiles were observed in lutein (P = 0.02), zeaxanthin (P = 0.02), and alpha-tocopherol (P = 0.03). The carotenoid findings in the overall population were because of the strong inverse association between serum micronutrients and lung cancer in females. Statistically significant odds ratios (ORs) comparing 4(th) to 1st quartiles in the female population were seen in lutein [OR, 0.31; confidence interval (CI), 0.13-0.75], zeaxanthin (OR, 0.31; CI, 0.12-0.77), and beta-cryptoxanthin (OR, 0.34; CI, 0.14-0.81). For prostate cancer, mean serum concentrations were lower in cases for all of the nutrients except alpha-carotene. Only for alpha-tocopherol (P(trend) = 0.04) were the findings statistically significant. There was no statistically significant association between serum carotenoids and prostate cancer. Our findings provide additional support for the association between physiological levels of dietary micronutrients and cancer incidence.
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PMID:The association between lung and prostate cancer risk, and serum micronutrients: results and lessons learned from beta-carotene and retinol efficacy trial. 1281 97

Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews and large well-designed original articles were preferred to form the basis of the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and in persons who have never smoked. Vitamin A, C and E supplements and beta-carotene offer no protection against the development of lung cancer. On the contrary, in two major randomised intervention trials beta-carotene supplement has resulted in increased mortality. Smoking remains by far the leading cause of lung cancer and the adverse effects can only be slightly alleviated by a healthy diet.
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PMID:[Diet and lung cancer]. 1297 Sep 95

Epidemiological studies suggested that vitamin A may be protective against lung cancer, however, recent chemoprevention trials with beta-carotene, a precursor of vitamin A, demonstrated enhancement of lung carcinogenesis among smokers. Whether vitamin A is beneficial or harmful in chemoprevention of lung cancer in smokers has not been resolved. This study was designed to determine the effect of retinol alone in current and former smokers using bronchial dysplasia, nuclear morphometry and retinoic acid receptor-beta (RAR-beta) mRNA expression as surrogate end-point biomarkers (SEBs). Eighty-one current or former smokers with a smoking history of >/=30 pack-years were randomized to receive either placebo or retinol (50,000 IU per day) for six months. Fluorescence bronchoscopy was performed prior to treatment to localize areas suggestive of dysplasia. At least 4 bronchial biopsies were taken per subject including at least two biopsies from apparently normal areas. The same areas were precisely re-biopsied after 6 months. Any new areas suggestive of dysplasia were also biopsied. Changes in the SEBs were assessed before and after treatment. At baseline, the frequency of biopsies negative for RAR-beta expression was: normal (23%), hyperplasia (28%), metaplasia (41%), mild dysplasia (41%), and moderate/severe dysplasia (44%). There was no significant difference in the regression rate between the retinol and placebo groups using histopathology and nuclear morphometry as SEBs. The likelihood of regression was found to be lower in those who continued to smoke during the study (OR=1.86 for those smoking >10 cigarettes per day, p=0.084 to OR=0.95, p=0.26 for those smoking 20+ per day compared to ex-smokers). Retinol was not effective in the up-regulation of RAR-beta in lesions with bronchial dysplasia. We postulate that the lack of effect of retinol on RAR-beta expression among individuals who continued to smoke while taking retinol may be due to suppressive effect of tobacco smoke constituents on RAR-beta expression and/or altered cellular metabolism of retinol to retinoic acid and its isomers.
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PMID:Surrogate end-point biomarker analysis in a retinol chemoprevention trial in current and former smokers with bronchial dysplasia. 1461 33

Pharmacologic or nutritional prevention of lung cancers is needed, especially for 60 million Americans who are former smokers. A portfolio of large-scale trials of beta-carotene, beta-carotene with and without vitamin E, and beta-carotene plus vitamin A demonstrated no benefit whatsoever from beta-carotene. The alpha-Tocopherol/beta-Carotene Trial and the beta-Carotene and Retinol Efficacy Trial found significant increases in lung cancer risk and total mortality. Laboratory research soon identified multiple adverse molecular effects. Nevertheless, chemoprevention remains an active, promising strategy, with new hypotheses and new candidate agents, including many already approved as therapies. The most active area currently is focused on selective inhibition of arachidonic metabolism, both Cox-2 and Lox pathways.
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PMID:Human lung cancer chemoprevention strategies: Parker B. Francis lecture. 1513 59

Increased physical activity has been associated with a reduction in the incidence and mortality from all-site cancer and some site-specific cancers in samples of primarily nonsmoking individuals; however, little is known about whether physical activity is associated with similar risk reductions among smokers and ex-smokers. This study examined physical activity in relation to all-site cancer and lung cancer incidence and mortality in a sample of current and former smokers (n = 7,045; 59% male; 95% Caucasian; mean age, 63 years) drawn from the beta-Carotene and Retinol Efficacy Trial, a lung cancer chemoprevention trial. Hazard rate ratios and 95% confidence intervals associated with a 1 SD increase in physical activity were 0.86 (0.80-0.94) for all-site cancer only among men, 0.84 (0.69-1.03) for lung cancer only for younger participants, 0.75 (0.59-0.94) for cancer mortality among younger participants and 0.68 (0.53-0.89) among women, and 0.69 (0.53-0.90) for lung cancer mortality only among women. These results suggest that incidence may be more attenuated by physical activity for men and mortality more attenuated for women. Effects may be more pronounced for younger people and may differ inconsistently by pack-years of smoking. Physical activity may play a role in reducing cancer risk and mortality among those with significant tobacco exposure. Prospective studies using more sophisticated measures of physical activity assessed at multiple time points during follow-up are needed to corroborate these associations.
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PMID:Physical activity in relation to all-site and lung cancer incidence and mortality in current and former smokers. 1559 85

Despite numerous published studies, debate continues regarding the risk of developing lung cancer among men exposed occupationally to asbestos, particularly those without radiographic or functional evidence of asbestosis. The beta-Carotene and Retinol Efficacy Trial (CARET), a study of vitamin supplementation for chemoprevention of lung cancer, has followed 4,060 heavily exposed US men for 9-17 years. Lung cancer incidence for 1989-2002 was analyzed using a stratified proportional hazards model. The study confirmed excessive rates of lung cancer among men with radiographic asbestosis. Comparison of study arms revealed a strong, unanticipated synergy between radiographic profusion category and the active intervention. In the large subgroup of men with normal lung parenchyma on chest radiograph at baseline, there was evidence of exposure-related lung cancer risk: Men with more than 40 years' exposure in high-risk trades had a risk approximately fivefold higher than men with 5-10 years, after adjustment for covariates. The effect in these men was independent of study intervention arm, but pleural plaques on the baseline radiograph and abnormal baseline flow rate were strong independent predictors of subsequent lung cancer. Residual confounding by subclinical asbestosis, exposure to unmeasured lung carcinogens, or differences in smoking are unlikely to explain these observations better than a carcinogenic effect of asbestos per se.
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PMID:Predictors of lung cancer among asbestos-exposed men in the {beta}-carotene and retinol efficacy trial. 1567 Dec 58


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