***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: CARET is a multicenter , two-armed , double-masked r and omized chemoprevention trial in Seattle , Portl and , San Francisco , Baltimore , Connecticut , and Irvine , to test whether oral administration of beta-carotene ( 30 mg/day ) plus retinyl palmitate ( 25,000 IU/day ) can decrease the incidence of lung cancer in high risk population s , namely , heavy smokers and asbestos-exposed workers . The intervention combines the antioxidant action of beta-carotene and the tumor suppressor mechanism of vitamin A. As of April 30 , 1993 , CARET had r and omized 1,845 participants in the 1985 - 1988 pilot phase plus 13,260 " efficacy " participants since 1989 ; of these , 4,000 are asbestos-exposed males and 11,105 are smokers and former smokers ( 44 % female ) . Accrual is complete everywhere except Irvine , which was the last center added ( 1991 ) , and the safety profile of the regimen to date has been excellent . With 14,420 smokers , 4,010 asbestos-exposed participants , and 114,100 person-years through February 1998 , we expect CARET to be capable of detecting a 23 % reduction in lung cancer incidence in the two population s combined and 27 , 49 , 32 , and 35 % reductions in the smokers , female smokers , male smokers , and asbestos-exposed subgroups , respectively . CARET is highly complementary to the alpha-tocopherol-beta-carotene study in Finl and and the Harvard Physicians Health Study ( beta-carotene alone ) in the National Cancer Institute portfolio of major cancer chemoprevention trials BACKGROUND : In observational studies , individuals with high intakes of fruits and vegetables containing beta-carotene experience lower risks of developing cancer . However , the few r and omized trials of beta-carotene supplementation show no overall benefits ; some even suggest harm . This trial was design ed to test the effects of  beta-carotene supplementation in women . METHODS : The Women 's Health Study is a r and omized , double-blind , placebo-controlled trial originally testing aspirin , vitamin E , and beta-carotene in the prevention of cancer and cardiovascular disease among 39 876 women aged 45 years or older . The beta-carotene component was terminated early after a median treatment duration of 2.1 years ( range = 0.00 - 2 . 72 years ) . Statistical tests were two-sided . RESULTS : Among women r and omly assigned to receive beta-carotene ( 50 mg on alternate days ; n = 19 939 ) or placebo ( n = 19 937 ) , there were no statistically significant differences in incidence of cancer , cardiovascular disease , or total mortality after a median of 4.1 years ( 2.1 years ' treatment plus another 2.0 years ' follow-up ) . There were 378 cancers in the beta-carotene group and 369 cancers in the placebo group ( relative risk [ RR ] = 1.03 ; 95 % confidence interval [ CI ] = 0.89 - 1 . 18 ) . There were no statistically significant differences for any site-specific cancer or during years 1 and 2 combined and years 3 and up combined . For cardiovascular disease , there were no statistically significant differences for myocardial infa rct ion ( 42 in the beta-carotene group versus 50 in the placebo group ) , stroke ( 61 versus 43 ) , deaths from cardiovascular causes ( 14 versus 12 ) , or the combined end point of these three events ( 116 versus 102 ; among women with more than one event , only the first was counted ) . Deaths from any cause were similar in the two groups ( 59 versus 55 ) . Among smokers at baseline ( 13 % of all women ) , there were no statistically significant differences in overall incidence of cancer ( RR = 1.11 ; 95 % CI = 0.78 - 1.58 ) or cardiovascular disease ( RR = 1.01 ; 95 % CI = 0 . 62 - 1.63 ) . CONCLUSION : Among apparently healthy women , there was no benefit or harm from beta-carotene supplementation for a limited period on the incidence of cancer and of cardiovascular disease BACKGROUND Evidence has accumulated from observational studies that people eating more fruits and vegetables , which are rich in beta-carotene ( a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver ) and retinol ( an alcohol chemical form of vitamin A ) , and people having higher serum beta-carotene concentrations had lower rates of lung cancer . The Beta-Carotene and Retinol Efficacy Trial ( CARET ) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate ( vitamin A ) taken daily against placebo in 18314 men and women at high risk of developing lung cancer . The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm ; there were 28 % more lung cancers and 17 % more deaths in the active intervention group ( active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate ) . Promptly after the January 18 , 1996 , announcement that the CARET active intervention had been stopped , we published preliminary findings from CARET regarding cancer , heart disease , and total mortality . PURPOSE We present for the first time results based on the pre-specified analytic method , details about risk factors for lung cancer , and analyses of subgroups and of factors that possibly influence response to the intervention . METHODS CARET was a r and omized , double-blinded , placebo-controlled chemoprevention trial , initiated with a pilot phase and then exp and ed 10-fold at six study centers . Cigarette smoking history and status and alcohol intake were assessed through participant self-report . Serum was collected from the participants at base line and periodically after r and omization and was analyzed for beta-carotene concentration . An Endpoints Review Committee evaluated endpoint reports , including pathologic review of tissue specimens . The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence , with weighting linearly to hypothesized full effect at 24 months after r and omization . Relative risks ( RRs ) were estimated by use of Cox regression models ; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake . O'Brien-Fleming boundaries were used for stopping criteria at interim analyses . Statistical significance was set at the .05 alpha value , and all P values were derived from two-sided statistical tests . RESULTS According to CARET 's pre-specified analysis , there was an RR of 1.36 ( 95 % confidence interval [ CI ] = 1.07 - 1.73 ; P = .01 ) for weighted lung cancer incidence for the active intervention group compared with the placebo group , and RR = 1.59 ( 95 % CI = 1.13 - 2.23 ; P = .01 ) for weighted lung cancer mortality . All subgroups , except former smokers , had a point estimate of RR of 1.10 or greater for lung cancer . There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake ( RR = 1.99 ; 95 % CI = 1.28 - 3.09 ; test for heterogeneity of RR among quartiles of alcohol intake has P = .01 , unadjusted for multiple comparisons ) and with large-cell histology ( RR = 1.89 ; 95 % CI = 1.09 - 3.26 ; test for heterogeneity among histologic categories has P = .35 ) , but not with base-line serum beta-carotene concentrations . CONCLUSIONS CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality . The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finl and CARET is a chemoprevention trial of beta-carotene and vitamin A with lung cancer as the primary outcome . Participants at high risk for lung cancer are drawn from two population s : asbestos-exposed workers and heavy smokers . The intervention is a daily combination of 30 mg beta-carotene and 25,000 IU vitamin A as retinyl palmitate .  Nearly 18,000 participants will be followed for a mean 6 years , yielding over 100,000 person-years of follow-up . We project that this sample size will have 80 % power to detect a 23 % decrease in the incidence of lung cancer cases . The purpose of this paper is to present the values of the key sample size parameters of CARET ; our schemes for monitoring CARET for sample size adequacy , incidence of side effects , and efficacy of the study vitamins ; an overview of the data collected ; and plans for the primary , secondary , and ancillary analyses to be performed at the end of the trial . These approaches to the design , monitoring , and analysis of CARET are applicable for many other prevention trials 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 sub clinical 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 BACKGROUND The Beta-Carotene and Retinol Efficacy Trial ( CARET ) tested the effect of daily beta-carotene ( 30 mg ) and retinyl palmitate ( 25,000 IU ) on the incidence of lung cancer , other cancers , and death in 18,314 participants who were at high risk for lung cancer because of a history of smoking or asbestos exposure . CARET was stopped ahead of schedule in January 1996 because participants who were r and omly assigned to receive the active intervention were found to have a 28 % increase in incidence of lung cancer , a 17 % increase in incidence of death and a higher rate of cardiovascular disease mortality compared with participants in the placebo group . METHODS After the intervention ended , CARET participants returned the study vitamins to their study center and provided a final blood sample . They continue to be followed annually by telephone and mail self-report .  Self-reported cancer endpoints were confirmed by review of pathology reports , and death endpoints were confirmed by review of death certificates . All statistical tests were two-sided . RESULTS With follow-up through December 31 , 2001 , the post-intervention relative risks of lung cancer and all-cause mortality for the active intervention group compared with the placebo group were 1.12 ( 95 % confidence interval [ CI ] = 0.97 to 1.31 ) and 1.08 ( 95 % CI = 0.99 to 1.17 ) , respectively . Smoothed relative risk curves for lung cancer incidence and all-cause mortality indicated that relative risks remained above 1.0 throughout the post-intervention follow-up . By contrast , the relative risk of cardiovascular disease mortality decreased rapidly to 1.0 after the intervention was stopped . During the post-intervention phase , females had larger relative risks of lung cancer mortality ( 1.33 versus 1.14 ; P = .36 ) , cardiovascular disease mortality ( 1.44 versus 0.93 ; P = .03 ) , and all-cause mortality ( 1.37 versus 0.98 ; P = .001 ) than males . CONCLUSIONS The previously reported adverse effects of beta-carotene and retinyl palmitate on lung cancer incidence and all-cause mortality in cigarette smokers and individuals with occupational exposure to asbestos persisted after drug administration was stopped although they are no longer statistically significant . Planned subgroup analyses suggest that the excess risks of lung cancer were restricted primarily to females , and cardiovascular disease mortality primarily to females and to former smokers Our aim was to describe a vitamin A-based cancer prevention program for former asbestos workers and to check for possible harmful effects by comparing rates of disease and death in study subjects with subjects who chose not to join . All subjects 
    Output:
    
REVIEW ER 'S CONCLUSIONS There is currently no evidence to support recommending vitamins such as alpha-tocopherol , beta-carotene or retinol , alone or in combination , to prevent lung cancer .
A harmful effect was found for beta-carotene with retinol at pharmacological doses in people with risk factors for lung cancer ( smoking and /or occupational exposure to asbestos ) .