***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: Epidemiological studies have consistently demonstrated a decrease in the risk of esophageal squamous cell carcinoma ( SCC )  associated with higher fruit and vegetable intake , although the association has been examined predominantly in case-control studies . Here , we conducted a population -based prospect i ve cohort study among middle-aged Japanese men . Lifestyle characteristics were investigated using a self-administered question naire , which included a vali date d food frequency question naire with 138 food and beverage items . We followed a total of 38,790 men aged 45 - 74 years . A Cox proportional hazards model was used to estimate the hazard ratios ( HRs ) and 95 % confidence intervals ( 95 % CIs ) for esophageal SCC , with adjustment for potential confounders . During 297,651 person-years of follow-up , a total of 116 men were newly diagnosed with esophageal SCC . An increase in consumption of total fruit and vegetables by 100 grams per day ( g/day ) was associated with an 11 % decrease in the incidence of esophageal SCC ( 95 % CI : 1 - 21 % ) . In particular , a higher intake of cruciferous vegetables was associated with a significant decrease in risk ( HR per 100 g/day : 0.44 ; 95 % CI : 0.23 - 0.82 ) . Stratified analyses revealed that the beneficial effect of fruits and vegetables was not able to completely offset the harmful effect of tobacco and alcohol . Our findings provide further evidence for the protective role of fruits and vegetables in the development of esophageal SCC . To effectively reduce the burden of this disease , however , priority should be placed on smoking and drinking cessation . Finally , cruciferous vegetables deserve further investigation as foods possibly effective in the prevention of esophageal SCC Purpose : Pharmacologic concentrations of ascorbate may be effective in cancer therapeutics . We hypothesized that ascorbate concentrations achievable with i.v . dosing would be cytotoxic in pancreatic cancer for which the 5-year survival is < 3 % . Experimental Design : Pancreatic cancer cell lines were treated with ascorbate ( 0 , 5 , or 10 mmol/L ) for 1 hour , then viability and clonogenic survival were determined . Pancreatic tumor cells were delivered s.c . into the flank region of nude mice and allowed to grow at which time they were r and omized to receive either ascorbate ( 4 g/kg ) or osmotically equivalent saline ( 1 mol/L ) i.p . for 2 weeks . Results : There was a time- and dose-dependent increase in measured H2O2 production with increased concentrations of ascorbate . Ascorbate decreased viability in all pancreatic cancer cell lines but had no effect on an immortalized pancreatic ductal epithelial cell line . Ascorbate decreased clonogenic survival of the pancreatic cancer cell lines , which was reversed by treatment of cells with scavengers of H2O2 . Treatment with ascorbate induced a caspase-independent cell death that was associated with autophagy . In vivo , treatment with ascorbate  inhibited tumor growth and prolonged survival . Conclusions : These results show that pharmacologic doses of ascorbate , easily achievable in humans , may have potential for therapy in pancreatic cancer . Clin Cancer Res ; 16(2 ) ; Esophageal cancer incidence and mortality rates in Linxian , China are among the highest in the world . We examined risk factors for esophageal squamous cell carcinoma ( ESCC ) , gastric cardia cancer ( GCC ) , and gastric noncardia cancer ( GNCC ) in a population -based , prospect i ve study of 29,584 adults who participated in the Linxian General Population Trial . All study participants completed a baseline question naire that included questions on demographic characteristics , personal and family history of disease , and lifestyle factors . After 15 years of follow-up , a total of 3,410 incident upper gastrointestinal cancers were identified , including 1,958 ESCC , 1,089 GCC and 363 GNCC . Cox proportional hazard models were used to estimate risks . Increased age and a positive family history of esophageal cancer ( including ESCC or GCC ) were significantly associated with risk at all 3 cancer sites . Additional risk factors for ESCC included being born in Linxian , increased height , cigarette smoking and pipe smoking ; for GCC , male gender , consumption of moldy breads and pipe smoking ; and for GNCC , male gender and cigarette smoking . Protective factors for ESCC included formal education , water piped into the home , increased consumption of meat , eggs and fresh fruits and increased BMI ; for GCC , formal education , water piped into the home , increased consumption of eggs and fresh fruits and alcohol consumption ; and for GNCC , increased weight and BMI . General socioeconomic status ( SES ) is a common denominator in many of these factors and improving SES is a promising approach for reducing the tremendous burden of upper gastrointestinal cancers in Linxian It is considered that fruit and vegetable ( F&V ) protect against oesophagus and gastric cancer ( GC ) . However , 2 recent meta‐analyses suggest that the strength of association on GC seems to be weaker for vegetables than for fruit and weaker in cohort than in case‐control studies . No evidence exists from cohort studies about adenocarcinoma of oesophagus ( ACO ) . In 521,457 men and women participating in the EPIC cohort in 10 European countries , information of diet and lifestyle was collected at baseline . After an average of 6.5 years of follow‐up , a total of 330 GC and 65 ACO , confirmed and classified by a panel of pathologists , was used for the analysis . We examined the relation between F&V intake and GC and ACO . A calibration study in a sub‐ sample was used to control diet measurement errors . In a sub‐ sample of cases and a r and om sample of controls , antibodies against Helicobacter pylori ( Hp ) were measured and interactions with F&V were examined in a nested case‐control study . We observed no association with total vegetable intake or specific groups of vegetables and GC risk , except for the intestinal type , where a negative association is possible regarding  total vegetable ( calibrated HR 0.66 ; 95 % CI 0.35–1.22 per 100 g increase ) and onion and garlic intake ( calibrated HR 0.70 ; 95 % CI 0.38–1.29 per 10 g increase ) . No evidence of association between fresh fruit intake and GC risk was observed . We found a negative but non significant association between citrus fruit intake and the cardia site ( calibrated HR 0.77 ; 95 % CI 0.47–1.22 per 100 g increase ) while no association was observed with the non‐cardia site . Regarding ACO , we found a non significant negative association for vegetable intake and for citrus intake ( calibrated HRs 0.72 ; 95 % CI 0.32–1.64 and 0.77 ; 95 % CI 0.46–1.28 per 100 and 50 g increase , respectively ) . It seems that Hp infection does not modify the effect of F&V intake . Our study supports a possible protective role  of vegetable intake in the intestinal type of GC and the ACO . Citrus fruit consumption may have a role in the protection against cardia GC and ACO . © 2005 Wiley‐Liss , Changing patterns of esophageal squamous cell carcinoma ( ESCC ) and esophageal adenocarcinoma ( EAC ) incidence worldwide suggest distinct etiologies . Although associations between fruit and vegetable intake and both ESCC and EAC have been found in multiple ecological and case-control studies , few prospect i ve studies have investigated these associations . We prospect ively examined these associations in 490,802 participants of the National Institutes of Health (NIH)-AARP Diet and Health Study using Cox models adjusted for age , alcohol intake , body mass index , cigarette smoking , education , physical activity and total energy intake .  We present hazard ratios and 95 % confidence intervals per serving per 1,000 calories . During 2,193,751 person years of follow-up , 103 participants were diagnosed with ESCC and 213 participants with EAC . We found a significant inverse association between total fruit and vegetable intake and ESCC risk ( HR : 0.78 , 95 % CI : 0.67 - 0.91 ) , but not EAC risk ( 0.98 , 0.90 - 1.08 ) . In models mutually adjusted for fruit and vegetable intake , the protective association with ESCC was stronger for fruits ( 0.73 , 0.57 - 0.93 ) than for vegetables ( 0.84 , 0.66 - 1.07 ) . When we examined botanical subgroups , we observed significant protective associations for ESCC and intake of Rosacea ( apples , peaches , nectarines , plums , pears and strawberries ) and Rutaceae ( citrus fruits ) . A significant inverse association between EAC and Chenopodiaceae ( spinach ) intake was observed . Results from our study suggest that the relation of  fruit and vegetable intake  and esophageal cancer risk may vary by histologic type Basic research and case – control studies have suggested that citrus consumption may protect against cancer . However , the protective effect has been observed from few prospect i ve studies . This study investigated the association of citrus consumption with cancer incidence among 42,470 Japanese adults in the Ohsaki National Health Insurance Cohort , which covered an age range of 40–79 years , and was followed up from 1995 to 2003 for all‐cancer and individual cancer incidence .  Citrus consumption was assessed using a self‐administered question naire . The Cox proportional hazard model was applied to estimate relative risks ( RRs ) and 95 % CIs . During the 323,204 person‐years of follow‐up , 3,398 cases were identified totally . Citrus consumption , especially daily consumption , was correlated with reduced all‐cancer incidence , the RRs were 0.89 ( 95 % CI = 0.80–0.98 ) for total participants , 0.86 ( 0.76–0.98 ) for males and 0.93 ( 0.79–1.09 ) for females , as well as multiple cancers at individual sites , especially pancreatic ( RR = 0.62 , 95 % CI = 0.38–1.00 ) and prostate cancer ( RR = 0.63 , 95 % CI = 0.41–0.97 ) . Joint effect analysis showed a reduced risk of overall cancer existed only for subjects who consumed ≥1 cup green tea/day ( RR = 0.83 , 95 % CI = 0.73–0.93 ) as well as for males ( RR = 0.83 , 95 % CI = 0.71–0.97 ) or females ( RR = 0.82 , 95 % CI = 0.68–0.99 ) . These findings suggest that citrus consumption is associated with reduced all‐cancer incidence , especially for subjects having simultaneously high green tea consumption . Further work on the specific citrus constituents is warranted , and clinical trials are ultimately necessary to confirm the protective effect Epidemiologic studies suggest that a high intake of fruits and vegetables is associated with decreased risk of cancers of the upper aero-digestive tract . We studied data from 345,904 subjects of the prospect i ve European Investigation into Cancer and Nutrition ( EPIC ) recruited in seven European countries , who had completed a dietary question naire in 1992–1998 . During 2,182,560 person years of observation 352 histologically verified incident squamous cell cancer ( SCC ) cases ( 255 males ; 97 females ) of the oral cavity , pharynx , larynx , and esophagus were identified . Linear and restricted cubic spline Cox regressions were fitted on variables of intake of fruits and vegetables and adjusted for potential confounders . We observed a significant inverse association with combined total fruits and vegetables intake ( estimated relative risk ( RR ) = 0.91 ; 95 % confidence interval ( 95 % CI ) 0.83–1.00 per 80 g/d of consumption ) , and nearly significant inverse associations in separate analyses with total fruits and total vegetables intake ( RR : 0.97 ( 95 % CI : 0.92–1.02 ) and RR = 0.89 ( 95 % CI : 0.78–1.02 ) per 40 g/d of consumption ) . Overall , vegetable subgroups were not related to risk with the exception of intake of root vegetables in men . Restricted cubic spline regression did not improve the linear model fits except for total fruits and vegetables and total fruits with a significant decrease in risk at low intake levels ( < 120 g/d ) for fruits . Dietary recommendations should consider the potential benefit of increasing fruits and vegetables consumption for reducing the risk of cancers of the upper aero-digestive tract , particularly at low intake Prospect i ve data on environmental exposures , especially with respect to alcohol , tobacco , and diet , in relation to the risk of esophageal cancer in high-risk population s are sparse . We analyzed data from a population -based cohort of 18,244 middle-aged and older men in Shanghai to identify risk factors for esophageal cancer in this 
    Output:
    
This meta- analysis indicates that intakes of citrus fruit significantly reduce the risk of ESCC and is no obvious relationship with EAC .