***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: Objective —C-reactive protein ( CRP ) concentrations are predictive of cardiovascular disease , and levels are heritable , in part . We identified novel polymorphisms in the CRP gene and assessed their influence on CRP level . Methods and Results —CRP was measured in 250 male army recruits before and after strenuous exercise and perioperatively in 193 coronary artery bypass graft ( CABG ) patients . Two novel polymorphisms were identified in the CRP gene , −717G > A in the promoter and + 1444C > T in the 3′UTR . Among army recruits , CRP was higher in + 1444TT homozygotes than + 1444 C-allele carriers at baseline ( 1.04±0.38 versus 0.55±0.06 , P = 0.014 ) and at all time points after exercise ( 2.35±0.68 versus 1.07±0.12 , 2.11±0.53 versus 0.88±0.09 , and 1.77±0.44 versus 0.71±0.09 , P = 0.034 , P = 0.007 , and P = 0.013 , at 2 , 48 , and 96 hours after exercise , respectively ) . In the CABG patients , mean CRP ( mg/L ) rose from 1.97±0.36 at baseline to 167.2±5.0 72 hours postoperatively . Genotype did not influence CRP at baseline ; however , peak post-CABG CRP levels were higher in + 1444TT homozygotes compared with + 1444C-allele carriers ( 198±17 versus 164±5 , P = 0.03 ) . Conclusions —The CRP gene + 1444C > T variant influences basal and stimulated CRP level . These findings have implication s both for the prediction and pathogenesis of coronary heart disease Associations between modifiable exposures and disease seen in observational epidemiology are sometimes confounded and thus misleading , despite our best efforts to improve the design and analysis of studies . Mendelian r and omization-the r and om assortment of genes from parents to offspring that occurs during gamete formation and conception-provides one method for assessing the causal nature of some environmental exposures . The association between a disease and a polymorphism that mimics the biological link between a proposed exposure and disease is not generally susceptible to the reverse causation or confounding that may distort interpretations of conventional observational studies . Several examples where the phenotypic effects of polymorphisms are well documented provide encouraging evidence of the explanatory power of Mendelian r and omization and are described . The limitations of the approach include confounding by polymorphisms in linkage disequilibrium with the polymorphism under study , that polymorphisms may have several phenotypic effects associated with disease , the lack of suitable polymorphisms for study ing modifiable exposures of interest , and canalization-the buffering of the effects of genetic variation during development . Nevertheless , Mendelian r and omization provides new opportunities to test causality and demonstrates how investment in the human genome project may contribute to underst and ing and preventing the adverse effects on human health of modifiable exposures Abstract The goals of our work were to study prospect ively the possibility of differentiating between infections and neoplastic fever in adult cancer patients on admission , by means of  C-reactive protein ( CRP ) and  erythrocyte sedimentation rate ( ESR ) or of follow-up  CRP values . Patients and methods were as follows : the final infection group consisted of 56 patients and the noninfection group of 10 patients with neoplastic fever ; CRP was measured on days 0 , 3 and 5 and ESR at entry . The main results showed that the median CRP did not differ between the groups ( 91 mg/l vs 102 mg/l ) on entry , while the ESR level was higher in the neoplastic fever group ( 50 mm/H vs 89 mm/H , P=0.023 ) . On admission , both markers had low area under receiver operating characteristic curves for the demonstration of infection ( CRP 0.42 ; ESR 0.27 ) . The CRP level dropped significantly in the infection group within 5 days ( P=0.009 ) . We conclude that neither of the markers was useful in differentiating between infections and neoplastic fever on admission , but that the follow-up CRP values were advantageous in this respect Background —C-reactive  protein ( CRP ) values predict atherothrombotic cardiovascular disease and type 2 diabetes mellitus . Associations between CRP and obesity , predominantly assessed anthropometrically , may partly explain these observations . Previous studies have been unable to control for genetic influences on CRP and obesity . The aim of this study was to examine the relationship between CRP and accurately measured body fat , lipids , apolipoproteins , blood pressure , and environmental and behavioral factors , independent of genetic influences . Methods and Results —One hundred ninety-four healthy female twins ( age 57.2±7 years ) were studied after excluding pairs with CRP values > 10 mg/L.  Total body fat and central abdominal fat ( CAF ) were measured by dual-energy x-ray absorptiometry .  CRP concentration was strongly related to surrogate and direct measures of body fat ( r = 0.31 to 0.54 , P < 0.001 ) , diastolic blood pressure ( r = 0.20 , P = 0.003 ) , and lipid and apolipoprotein levels ( r = 0.21 to 0.51 , P < 0.008 ) . Light-to-moderate alcohol consumers and nonusers of hormone replacement therapy ( HRT ) had lower CRP levels than abstainers and HRT users , respectively . In stepwise multiple regression analysis , CAF , triglycerides , apolipoprotein B , and HRT  use explained 46 % of the variance in circulating CRP . In analyses controlling for genetic influences in monozygotic twins , within-pair differences in CRP were associated with within-pair differences in total body fat ( r = 0.39 , P < 0.001 ) , CAF ( r = 0.34 , P = 0.002 ) , diastolic blood pressure ( r = 0.24 , P = 0.03 ) , apolipoprotein AI ( r = −0.33 , P = 0.01 ) , HDL cholesterol ( r = −0.42 , P = 0.001 ) , and triglycerides ( r = 0.35 , P = 0.007 ) . Conclusions —CRP was strongly related to total and central abdominal obesity , blood pressure , and lipid levels , independent of genetic influences . These relationships are likely to contribute significantly to prospect i ve associations between CRP and type 2 diabetes and coronary events Summary Retrospective analysis previously identified significant elevation of five tumour markers , carcinoembryonic antigen ( CEA ) , ferritin , orosomucoid , C-reactive protein and erythrocyte sedimentation rate ( ESR ) , in patients with systemic breast cancer and showed that changes in each of these markers individually correlated significantly with therapeutic response . In this study we have prospect ively tested these findings . None of the five markers was significantly elevated in primary breast cancer compared to normal control or benign breast disease groups . They therefore appear to have no role either in screening or in the differential diagnosis of breast cancer . There was a significant elevation of all five markers in patients with systemic breast cancer ( P < 0.0001 ; analysis of variance ) but sequential changes in CEA and ESR only correlated significantly with the UICC-assessed response . Prospect i ve confirmation of the correlation between changes in serum CEA and ESR provides the basis for using these markers in the assessment of response to therapy in patients with systemic breast cancer Preoperative biliary drainage may improve the cytokine and acute-phase response derangements observed in patients with obstructive jaundice . We conducted a prospect i ve longitudinal , before-after trial in our 600-bed teaching hospital . Twenty-four patients with obstructive jaundice were investigated , 11 with benign obstruction and 13 with malignant disease .  Endoscopic internal biliary drainage was performed in all patients ( 7 by papillotomy  and 17 by endoprostheses )  . Endotoxin , tumor necrosis factor alpha ( TNF-α ) , interIeukin-6 ( IL-6 ) , nitric oxide production , and C-reactive protein ( CRP ) were determined at admission and on days 2 and 7 after internal biliary drainage was accomplished . Bile cultures were obtained before and at the time of drainage . Endotoxin , IL-6 , TNF-α , and CRP were significantly higher in patients with cancer . After internal drainage , endotoxin ( 11.4 vs. 2 EU/L ; p<0.05 ) , TNF-α ( 87.5 vs. 48 pg/ml ; p=0.03 ) , and IL-6 ( 324 vs. 232 pg/ml;/ p<0.05 ) plasma levels decreased significantly in the early postdrainage period in patients with cancer  . Endotoxin , cytokines , as well as the CRP plasma values , however , increased again on day 7 after drainage . This trend was less marked in patients with benign obstruction . Patients with positive bile cultures after drainage displayed higher levels of CRP ( 115 vs. 62 mg/L ; p=0.03 ) , IL-6 ( 598 vs. 330 pg/ml ; p=0.04 ) , and endotoxin ( 10.6 vs. 4.8 EU/L ; p=0.02 ) than those with negative bile cultures . Biliary tract obstruction is associated with an increase in endotoxin levels , a positive acute-phase response , and plasma cytokine elevation . After biliary drainage a transitory improvement of these alterations was observed , although values remained high 1 week postdrainage . These findings were associated with positive bile cultures . RésuméLe drainage biliaire préopératoire peut améliorer les perturbations des cytokines et celles observées dans la réponse de la phase aiguë chez les patients atteints d’ictère obstructif . Cette étude , prospect i ve , longitudinale , a consisté à étudier 24 patients atteints d’ictère obstructif , 11 d’origine bénigne , 13 d’origine maligne , avant et après traitement dans un Hôpital Universitaire de 600 lits . Les interventions comportaient toujours un drainage endoscopique interne ( 7 papillotomies et 17 endoprothèses ) . On a mesuré l’endotoxine , le facteur TNF-α , l’IL-6 , la production en oxyde nitrique et la C-réactive protéine ( CRP ) au moment de l’admission et aux jours 2 et 7 après drainage biliaire interne . Des cultures ont été obtenues avant et au moment du drainage . Les taux d’endotoxine , de l’IL-6 , du TNF-α et de la CRP étaient significativement plus élevés chez les patients atteints de cancer . Après drainage interne , les taux plasmatiques de l’endotoxine ( 11.4 vs. 2 EU/L ; p<0.05 ) , de TNF-α ( 87.5 vs. 48 pg/ml ; p=0.03 ) et d’IL-6 ( 324 vs. 232 pg/ml ; p<0.05 ) ont diminué de façon significative après drainage chez les patients atteints de cancer .  Les taux d’endotoxine et des cytokines tout comme les taux plasmatiques de la CRP ont cependant augmenté au jour sept . Cette tendance a été moins marquée chez les patients porteurs d’obstruction bénigne . Les patients ayant des cultures de bile positives après drainage avaient un taux postdrainage plus élevé de CRP ( 115 vs. 62 mg/L ; p=0.03 ) , d’IL-6 ( 598 vs. 330 pg/ml ; p=0.04 ) et d’endotoxine ( 10.6 vs. 4.8 EU/L ; p=0.02 ) que ceux ayant des cultures de bile négatives . L’obstruction biliaire est associée à une augmentation des taux d’endotoxines , à une réponse de phase aiguë positive et à une élévation des cytokines plasmatiques . Après drainage biliaire , on observe une amélioration transitoire de ces altérations , même si les valeurs restaient élevées une semaine après le drainage , surtout en cas de cultures de bile positives . ResumenEn pacientes ictéricos , el drenaje biliar preoperatorio parece mejorar las atocinas y las alteraciones de respuesta de la fase aguda . En un Hospital Universitario de 600 camas , se diseñó un estudio clínico prospect ivo longitudinal . Se estudiaron 24 pacientes con ictericia obstructiva : La obstrucción era benigna en 11 y maligna en 13 . El drenaje biliar interno se realizó por vía endoscópica ( 7 papilotomías y 17 endoprótesis ) . El día del ingreso y a los 2 y 7 días del drenaje biliar interno se determinaron : endotoxina , TNF-α , IL-6 , producción de óxido nítrico y proteína C reactiva ( CRP ) . Las endotoxina , IL- 
    Output:
    
The prospect i ve studies provided no strong evidence for a causal role of  CRP  in cancer .