***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: Genome-wide DNA hypomethylation plays has an important role in genomic instability and colorectal carcinogenesis . However , the relationship between cellular DNA methylation level and patient outcome remains uncertain . Using 643 colon cancers in two independent prospect i ve cohorts , we quantified DNA methylation in repetitive long interspersed nucleotide element-1 ( LINE-1 ) elements using pyrosequencing , which is a good indicator of global DNA methylation level . We used Cox proportional hazard models to calculate hazard ratios ( HRs ) of colon cancer-specific and overall mortality , adjusting for patient and tumoral features , including CpG isl and methylator phenotype ( CIMP ) . Statistical tests were two-sided . LINE-1 hypomethylation was linearly associated with a statistically significant increase in colon cancer-specific mortality ( for a 30 % decrease in LINE-1 methylation : multivariable HR = 2.37 , 95 % confidence interval [ CI ] = 1.42 to 3.94 ; P(trend ) < .001 ) and overall mortality ( multivariable HR = 1.85 , 95 % CI = 1.25 to 2.75 ; P(trend ) = .002 ) . The association was consistent across the two independent cohorts and strata of clinical and molecular characteristics , including sex , age , tumor location , stage , and CIMP , microsatellite instability , KRAS , BRAF , p53 , and chromosomal instability status . In conclusion , tumoral LINE-1 hypomethylation is independently associated with shorter survival among colon cancer patients Responses of patients with gliomas to temozolomide  are determined by O6-methylguanine-DNA methyltransferase ( MGMT ) and mismatch repair ( MMR ) pathways . This phase II study ( NCT00423150 ) investigated whether MGMT promoter methylation predicts response in patients with advanced aerodigestive tract and colorectal cancers ( CRC ) . Tumor and serum sample s were screened for MGMT promoter methylation . In methylation-positive patients , 150 mg/m2 temozolomide was administered daily on a seven-day-on , seven-day-off schedule for each 28-day cycle . The primary efficacy endpoint was response rate ( RR ) . MMR status was determined by a microsatellite instability assay . Among 740 patients screened , 86 were positive for MGMT promoter methylation and enrolled . Nineteen percent of the screened population ( 137/740 ) had confirmed tissue and /or serum MGMT promoter methylation , including 25 % ( 57 of 229 ) for CRC , 36 % ( 55 of 154 ) for esophageal cancer , 11 % ( 12 of 113 ) for head and neck cancer , and 5 % ( 13 of 242 ) for non – small cell lung carcinoma . Among patients with valid methylation results in both tissue and serum sample s , concordance was 81 % ( 339 of 419 ) . The majority of enrolled patients ( 69 of 86 ; 80 % ) had microsatellite stable cancer . Overall RR was 6 % ( 5 of 86 partial responses ) ; all responders had microsatellite stable cancer . Temozolomide result ed in low RRs in patients enriched for MGMT methylation . MGMT methylation status varied considerably in the patient population . Although serum methylation assay is an option for promoter methylation detection , tissue assay remains the st and ard for methylation detection . The low RR of this cohort of patients indicates that MGMT methylation as a biomarker is not applicable to heterogeneous tumor types , and tumor-specific factors may override vali date d biomarkers . Mol Cancer Ther ; 12(5 ) ; 809–18 . © 2013 AACR Purpose : Radiotherapy followed by total mesorectal excision surgery has been shown to significantly reduce local recurrence rates in rectal cancer patients .  Radiotherapy , however , is associated with considerable morbidity . The present study evaluated the use of biochemical detection of enzymatic caspase-3 activity as preoperative marker for apoptosis to preselect patients that are unlikely to develop a local recurrence to spare these patients from overtreatment and the negative side effects of radiotherapy . Experimental Design : Nonirradiated freshly frozen tissue sample s from 117 stage III rectal cancer patients were collected from a r and omized clinical trial that evaluated preoperative radiotherapy in total mesorectal excision surgery . Additional frozen archival tissues from 47 preoperative biopsies and corresponding resected colorectal tumors were collected . Level of apoptosis was determined by measuring the enzymatic activity of caspase-3 in a biochemical assay . Results : In tumor tissue , caspase-3 activity lower than the median was predictive of 5-year local recurrence ( hazard ratio , 7.4 ; 95 % confidence interval , 1.7 - 32.8 ; P = 0.008 ) , which was unaffected by adjustment for type of resection , tumor location , and T status ( adjusted hazard ratio , 7.5 ; 95 % confidence interval , 1.7 - 34.1 ; P = 0.009 ) . Caspase-3 activity in preoperative biopsies was significantly correlated with caspase-3 activity in corresponding resected tumors ( r = 0.56 ; P < 0.0001 ) . Conclusion : Detection of tumor apoptosis levels by measuring caspase-3 activity , for which a preoperative biopsy can be used , accurately predicted local recurrence in rectal cancer patients . These findings indicate that caspase-3 activity is an important denominator of local recurrence and should be evaluated prospect ively to be added to the criteria to select rectal cancer patients in which radiotherapy is redundant BACKGROUND & AIMS Despite poor performance , guaiac-based fecal occult blood tests ( G-FOBT ) are most frequently implemented for colorectal cancer screening . Immunochemical fecal occult blood tests ( I-FOBT ) are cl aim ed to perform better , without r and omized comparison in screening population s. Our aim was to r and omly compare G-FOBT with I-FOBT in a screening population . METHODS We conducted a population -based study on a r and om sample of 20,623 individuals 50 - 75 years of age , r and omized to either G-FOBT ( Hemoccult-II ) or I-FOBT ( OC-Sensor ) .  Tests and invitations were sent together . For I-FOBT , the st and ard cutoff of 100 ng/ml was used . Positive FOBTs were verified with colonoscopy . Advanced adenomas were defined as > or=10 mm , high- grade dysplasia , or > or=20 % villous component . RESULTS There were 10,993 tests returned : 4836 ( 46.9 % ) G-FOBTs and 6157 ( 59.6 % ) I-FOBTs . The participation rate difference was 12.7 % ( P < .01 ) . Of G-FOBTs , 117 ( 2.4 % ) were positive versus 339 ( 5.5 % ) of I-FOBTs . The positivity rate difference was 3.1 % ( P < .01 ) . Cancer and advanced adenomas were found , respectively , in 11 and 48 of G-FOBTs and in 24 and 121 of I-FOBTs . Differences in positive predictive value for cancer and advanced adenomas and cancer were , respectively , 2.1 % ( P = .4 ) and -3.6 % ( P = .5 ) . Differences in specificities favor G-FOBT and were , respectively , 2.3 % ( P < .01 ) and -1.3 % ( P < .01 ) . Differences in intention-to-screen detection rates favor I-FOBT and were , respectively , 0.1 % ( P < .05 ) and 0.9 % ( P < .01 ) . CONCLUSIONS The number-to-scope to find 1 cancer was comparable between the tests . However , participation and detection rates for advanced adenomas and cancer were significantly higher for I-FOBT . G-FOBT significantly underestimates the prevalence of advanced adenomas and cancer in the screening population compared with I-FOBT 
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For diagnostic purpose s , the most independently vali date d genes to study further are VIM , SEPT9 , ITGA4 , OSM4 , GATA4 and NDRG4 .
In terms of prognostic markers , myopodin , KISS1 , TMEFF2 , HLTF , hMLH1 , APAF1 , BCL2 and p53 are independently vali date d. Most prognostic markers published lack both a multivariate analysis in comparison to clinical risk factors and the appropriate patient group who will benefit by adjuvant chemotherapy .
Methylation of IGFBP3 , mir148a and PTEN are found to be predictive markers for 5-FU and EGFR therapy respectively .