BackgroundColorectal cancer (CRC) is one of the most common cancers in the western world. Screening is an efficient method of reducing cancer-related mortality. Molecular biomarkers for cancer in general and CRC in particular have been proposed, and hypermethylated DNA from stool or blood samples are already implemented as biomarkers for CRC screening.We aimed to evaluate the performance of proven hypermethylated DNA promoter regions as plasma based biomarkers for CRC detection.MethodsWe conducted a cross-sectional case-control study of 193 CRC patients and 102 colonoscopy-verified healthy controls. Using methylation specific polymerase chain reaction, we evaluated 30 DNA promoter regions previously found to be CRC specific. We used multivariable logistic regression with stepwise backwards selection, and subsequent leave-pair-out cross validation, to calculate the optimism corrected area under the receiver operating characteristics curve (AUC) for all stage as well as early stage CRC.ResultsNone of the individual DNA promoter regions provided an overall sensitivity above 30% at a reasonable specificity. However, seven hypermethylated promoter regions (ALX4, BMP3, NPTX2, RARB, SDC2, SEPT9, and VIM) along with the covariates sex and age yielded an optimism corrected AUC of 0.86 for all stage CRC and 0.85 for early stage CRC. Overall sensitivity for CRC detection was 90.7% at 72.5% specificity using a cut point value of 0.5.ConclusionsIndividual hypermethylated DNA promoter regions have limited value as CRC screening markers. However, a panel of seven hypermethylated promoter regions show great promise as a model for CRC detection.
Hypermethylation of the promoters of specific genes measured in blood or stool samples could be used as a CRC biomarker and provide prognostic information. The majority of studies, however, include only a few patients with poorly defined control groups. Further studies are therefore needed before hypermethylated DNA can be widely applied as a clinical biomarker for CRC detection and prognosis.
Background: This study aimed to evaluate the effect of perioperative supplementation with omega-3 fatty acids (n-3 FA) on perioperative outcomes and survival in patients undergoing colorectal cancer surgery. Methods: Patients scheduled for elective resection of colorectal cancer between 2007 and 2010 were randomized to either an n-3 FA-enriched oral nutrition supplement (ONS) twice daily or a standard ONS (control) for 7 days before and after surgery. Outcome measures, including postoperative complications, 3-year cumulative incidence of local or metastatic colorectal cancer recurrence and 5-year overall survival, were compared between the groups. Results: Of 148 patients enrolled in the study, 125 (65 patients receiving n-3 FA-enriched ONS and 60 receiving standard ONS) were analysed. There were no differences in postoperative complications after surgery (P = 0⋅544). The risk of disease recurrence at 3 years was similar (relative risk 1⋅66, 95 per cent c.i. 0⋅65 to 4⋅26).The 5-year survival rate of patients treated with n-3 FA was 69⋅2 (95 per cent c.i. 56⋅5 to 78⋅9) per cent, compared with 81⋅7 (69⋅3 to 89⋅4) per cent in the control group (P = 0⋅193). After adjustment for age, stage of disease and adjuvant chemotherapy, n-3 FA was associated with higher mortality compared with controls (hazard ratio 1⋅73, 95 per cent c.i. 1⋅06 to 2⋅83; P = 0⋅029). The interaction between n-3 FA and adjuvant chemotherapy was not statistically significant. Conclusion: Perioperative supplementation with n-3 FA did not confer a survival benefit in patients undergoing colorectal cancer surgery. n-3 FA did not benefit the subgroup of patients treated with adjuvant chemotherapy or decrease the risk of disease recurrence.
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