***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: Use of statins is hypothesized to reduce  colorectal cancer risk but the evidence remains inconsistent . This may be partly explained by differential associations according to tumor location or molecular subtypes of colorectal cancer . We examined the association between statin use and colorectal cancer risk according to tumor location , KRAS mutation status , microsatellite instability ( MSI ) status , PTGS2 ( COX-2 ) expression , or CpG isl and methylator phenotype ( CIMP ) status in two large prospect i ve cohort studies , the Nurses ' Health Study and Health Professionals Follow-up Study . We applied Cox regression to a competing risks analysis . We identified 1,818 colorectal cancers during 1990 to 2006 . Compared with nonusers , current statin use was not associated with colorectal cancer [ relative risk ( RR ) = 0.99 , 95 % CI = 0.86–1.14 ] or colon cancer ( RR = 1.10 , 95 % CI = 0.94–1.29 ) but was inversely associated with rectal cancer ( RR = 0.59 , 95 % CI = 0.41–0.84 , Pheterogeneity < 0.001 ) . When we examined the association within strata of KRAS mutation status , we found no association with KRAS-mutated cancers ( RR = 1.20 , 95 % CI = 0.87–1.67 ) but did observe a possible inverse association among KRAS wild-type cancers ( RR = 0.80 , 95 % CI = 0.60–1.06 , Pheterogeneity = 0.06 ) . The association did not substantially differ by PTGS2 expression , MSI status , or CIMP status . Current statin use was not associated with risk of overall colorectal cancer . The possibility that statin use may be associated with lower risk of rectal cancer or KRAS wild-type colorectal cancer requires further confirmation . Cancer Prev Res ; 4(11 ) ; 1808–15 . © 2011 AACR The authors compared five methods of study ing survival bias associated with time-to-treatment initiation in a drug effectiveness study using medical administrative data bases ( 1996 - 2002 ) from Quebec , Canada . The first two methods illustrated how survival bias could be introduced . Three additional methods were considered to control for this bias . Methods were compared in the context of evaluating statins for secondary prevention in elderly patients post-acute myocardial infa rct ion who initiated statins within 90 days after discharge and those who did not . Method 1 that classified patients into users and nonusers at discharge result ed in an overestimation of the benefit ( 38 % relative risk reduction at 1 year ) . In method 2 , following users from the time of the first prescription and nonusers from a r and omly selected time between 0 and 90 days attenuated the effect toward the null ( 10 % relative risk reduction ) . Method 3 controlled for survival bias by following patients from the end of the 90-day time window ; however , it suffered a major loss of statistical efficiency and precision . Method 4 matched prescription time distribution between users and nonusers at cohort entry . Method 5 used a time-dependent variable for treatment initiation . Methods 4 and 5 better controlled for survival bias and yielded similar results , suggesting a 20 % risk reduction of recurrent myocardial infa rct ion or death events Epidemiologists are aware that the estimated effect of an exposure can be biased if the investigator fails to adjust for confounding factors when analyzing either a prospect i ve or retrospective etiologic study . St and ard texts warn , however , that intervening factors are an exception : one should not adjust for any factor which is intermediate on the causal pathway between the exposure and the disease . Other factors which are not on the causal pathway but are caused in part by the exposure are often adjusted for in epidemiologic studies . This paper illustrates that bias can result when adjustment is made for any factor which is caused in part by the exposure under study and is also correlated with the outcome under study . Intervening variables are only one example of this phenomenon . The misleading effects of this practice are illustrated with examples Background An association between tumor-specific HMG-CoA reductase ( HMGCR ) expression and good prognosis has previously been demonstrated in breast and ovarian cancer . In this study , the expression , clinicopathological correlates and prognostic value of HMGCR expression in colorectal cancer was examined . Findings Immunohistochemical expression of  HMGCR  was assessed in tissue microarrays with primary tumours from 557 incident cases of colorectal cancer in the Malmö Diet and Cancer Study . Pearson ’s Chi Square test was applied to explore the associations between HMGCR expression and clinicopathological factors and other investigative biomarkers . Kaplan Meier analysis and Cox proportional hazards modeling were used to assess the relationship between HMGCR expression and cancer-specific survival ( CSS ) according to negative vs positive HMGCR expression . A total number of 535 ( 96.0 % ) tumours were suitable for analysis , of which 61 ( 11.4 % ) were HMGCR negative . Positive cytoplasmic HMGCR expression was associated with distant metastasis-free disease at diagnosis ( p = 0.002 ) , lack of vascular invasion ( p = 0.043 ) , microsatellite-instability ( p = 0.033 ) , expression of cyclin D1 ( p = < 0.001 ) and p21 ( p = < 0.001 ) . Positive HMGCR expression was significantly associated with a prolonged CSS in unadjusted Cox regression analysis in the entire cohort ( HR = 1.79 ; 95 % CI 1.20 - 2.66 ) and in Stage III-IV disease ( HR = 1.71 ; 95 % CI 1.09 - 2.68 ) , but not after adjustment for established clinicopathological parameters . Conclusions Findings from this prospect i ve cohort study demonstrate that HMGCR is differentially expressed in colorectal cancer and that positive expression is associated with favourable tumour characteristics and a prolonged survival in unadjusted analysis . The utility of HMGCR as a predictor of response to neoadjuvant or adjuvant statin treatment in colorectal cancer merits further study .Virtual slidesThe virtual slides for this article can be found here : http://www.diagnosticpathology.diagnomx.eu/vs/2115647072103464 BACKGROUND The st and ard adjuvant treatment of colon cancer is fluorouracil plus leucovorin ( FL ) . Oxaliplatin improves the efficacy of this combination in patients with metastatic colorectal cancer . We evaluated the efficacy of treatment with FL plus oxaliplatin in the postoperative adjuvant setting . METHODS We r and omly assigned 2246 patients who had undergone curative resection for stage II or III colon cancer to receive FL alone or with oxaliplatin for six months . The primary end point was disease-free survival . RESULTS A total of 1123 patients were r and omly assigned to each group . After a median follow-up of 37.9 months , 237 patients in the group given FL plus oxaliplatin had had a cancer-related event , as compared with 293 patients in the FL group ( 21.1 percent vs. 26.1 percent ; hazard ratio for recurrence , 0.77 ; P=0.002 ) . The rate of disease-free survival at three years was 78.2 percent ( 95 percent confidence interval , 75.6 to 80.7 ) in the group given FL plus oxaliplatin and 72.9 percent ( 95 percent confidence interval , 70.2 to 75.7 ) in the FL group ( P=0.002 by the stratified log-rank test ) . In the group given FL plus oxaliplatin , the incidence of febrile neutropenia was 1.8 percent , the incidence of gastrointestinal adverse effects was low , and the incidence of grade 3 sensory neuropathy was 12.4 percent during treatment , decreasing to 1.1 percent at one year of follow-up . Six patients in each group died during treatment ( death rate , 0.5 percent ) . CONCLUSIONS Adding oxaliplatin to a regimen of fluorouracil and leucovorin improves the adjuvant treatment of colon cancer PURPOSE Aspirin and other nonsteroidal anti-inflammatory drugs ( NSAIDs ) protect against colorectal cancer ( CRC ) and are associated with reduced disease recurrence and improved outcome after primary treatment . However , toxicities of NSAIDs have limited their use as antineoplastic therapy . Recent data have suggested that the benefit of aspirin after CRC diagnosis is limited to patients with PIK3CA-mutant cancers . We sought to determine the predictive utility of PIK3CA mutation for benefit from both cyclooxygenase-2 inhibition and aspirin . METHODS We performed molecular analysis of tumors from 896 participants in the Vioxx in Colorectal Cancer Therapy : Definition of Optimal Regime ( VICTOR ) trial , a large r and omized trial comparing rofecoxib with placebo after primary CRC resection . We compared relapse-free survival and overall survival between rofecoxib therapy and placebo and between the use and nonuse of low-dose aspirin , according to tumor PIK3CA mutation status . RESULTS We found no evidence of a greater benefit from  rofecoxib treatment compared with placebo in patients whose tumors had PIK3CA mutations ( multivariate adjusted hazard ratio [ HR ] , 1.2 ; 95 % CI , 0.53 to 2.72 ; P = .66 ; (P)INTERACTION = .47 ) compared with patients with PIK3CA wild-type cancers ( HR , 0.87 ; 95 % CI , 0.64 to 1.16 ; P = .34 ) . In contrast , regular aspirin use after CRC diagnosis was associated with a reduced rate of CRC recurrence in patients with PIK3CA-mutant cancers ( HR , 0.11 ; 95 % CI , 0.001 to 0.832 ; P = .027 ; (P)INTERACTION = .024 ) but not in patients lacking tumor PIK3CA mutation ( HR , 0.92 ; 95 % CI , 0.60 to 1.42 ; P = .71 ) . CONCLUSION Although tumor PIK3CA mutation does not predict benefit from rofecoxib treatment , it merits further evaluation as a predictive biomarker for aspirin therapy . Our findings are concordant with recent data and support the prospect i ve investigation of adjuvant aspirin in PIK3CA-mutant CRC BACKGROUND Although pre clinical and epidemiological data suggest that statins may have antineoplastic properties , the impact of statin use on patient survival after a curative resection of stage III colon cancer is unknown . METHODS We conducted a prospect i ve observational study of 842 patients with stage III colon cancer enrolled in a r and omized adjuvant chemotherapy trial from April 1999 to May 2001 to investigate the relationship between statin use and survival . Disease-free survival ( DFS ) , recurrence-free survival ( RFS ) , and overall survival ( OS ) were investigated by Kaplan-Meier curves and log-rank tests in the overall study population and in a subset of patients stratified by KRAS mutation status ( n = 394 ) , and Cox proportional hazards regression was used to assess the simultaneous impact of confounding variables . All statistical tests were two-sided . RESULTS Among 842 patients , 134 ( 15.9 % ) reported statin use after completing adjuvant chemotherapy .  DFS among statin users and nonusers was similar ( hazard ratio [ HR ] of cancer recurrence or death = 1.04 , 95 % confidence interval [ CI ] = 0.73 to 1.49 ) . RFS and OS were also similar between statin users and nonusers ( adjusted HR of cancer recurrence = 1.14 , 95 % CI = 0.77 to 1.69 ; adjusted HR of death = 1.15 , 95 % CI = 0.77 to 1.71 ) . Survival outcomes were similar regardless of increasing duration of statin use before cancer diagnosis ( P(trend ) = .63 , .63 , and .59 for DFS , RFS , and OS , respectively ) . The impact of  statin  use did not differ by tumor KRAS mutation status , with similar DFS , RFS , and OS for statin use among mutant and wild-type subgroups ( P(interaction ) = .84 , .67 , and .98 for DFS , RFS , and OS , respectively ) . CONCLUSION Statin use during and after adjuvant chemotherapy was not associated with improved DFS , RFS , or OS  in patients with stage III colon cancer , regardless of KRAS mutation status BACKGROUND : Achieving a pathologic complete response to neoadjuvant chemoradiation improves prognosis in rectal cancer .  Statin therapy has been shown to enhance the impact of treatment in several malignancies , but little is known regarding the impact on rectal cancer response to neoadjuvant chemoradiation . OBJECTIVE : The purpose of this study was to determine whether statin use during neoadjuvant chemoradiation improves pathologic response in rectal cancer . DESIGN : This was a retrospective cohort study based on data from a prospect ively maintained colorectal cancer data base . The 2 cohorts were defined by statin use during neoadjuvant chemoradiation . SETTING : This study 
    Output:
    
In a Scottish CRC cohort and up date d meta- analysis there was some evidence that statin use was associated with improved survival .
However , these associations were weak in magnitude and , particularly for post-diagnosis use , varied markedly between studies