Abstract. Colorectal cancer (CRC) is one of the most common and deadly forms of cancer. Despite improved treatment modalities, post-operative recurrence and metastasis remain the major problems for extending patient survival after surgery. This highlights the need to search for biomarkers for prognostication and treatment stratification of colorectal cancer patients. In this study, we applied the SYBR-green quantitative PCR-based array approach to screen for differentially expressed miRNAs between patients with short (<50 months, range 10-33 months) and long survival (≥50 months, range 50-152 months). The selected candidate prognostic miRNAs were validated in a cohort of 50 CRC patients by TaqMan quantitative PCR. We found that high expression of miR-185 and low expression of miR-133b were correlated with poor survival (p=0.001 and 0.028, respectively) and metastasis (p=0.007 and 0.036, respectively) in colorectal cancer. Our findings suggest the potential prognostic values of these miRNAs for predicting clinical outcome after surgery. IntroductionColorectal cancer (CRC) is the second most common cancer in women and the third in men worldwide (1). It ranks the second most common cause of cancer death in the Western world (2). Currently, there are several treatment modalities for CRC, including surgery, radiotherapy, chemotherapy and targeted therapy (e.g., cetuximab). However, the long-term survival remains low in metastatic disease (3).Given that CRC usually follows a stepwise progression from benign to malignant lesion and distant metastasis, there is a possibility for early diagnosis in order to reduce morbidity and mortality. The commonly used method to characterize CRC tumor in clinic is T1-T3 staging system. However, the staging system reflects only morphological characteristics of the tumor and does not consider tumor molecular biology, thus, it is inaccurate in predicting the future outcome for each particular case. Therefore, the development of screening tools and new biomarkers to facilitate early diagnosis is particularly warranted. Further investigations in the search for new prognostic biomarkers may help to improve post-operative treatment approaches for CRC patients.Several studies have documented a link between the aberrant expression of a class of small non-coding RNAs, termed microRNAs (miRNAs), and the pathogenesis/prognosis of several cancer types, including colorectal cancer (4,5). These molecules provide a potentially valuable diagnostic/prognostic tool for CRC pathology, because mature miRNA species are relatively more stable than mRNAs and well preserved in formalin-fixed, paraffin-embedded samples which are commonly used in clinical routine (6). Furthermore, only a small number of miRNAs are required to distinguish cancerous tissues from non-cancerous tissues compared with mRNA profiles (7), which makes them more feasible candidate biomarkers.miRNAs are endogenous single-stranded non-coding RNAs of ~22-nucleotides in length, which are generated by an RNase III enzyme Dicer from endogenou...

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Background:Recently, several genome-wide association studies (GWAS) have independently found numerous loci at which common single-nucleotide polymorphisms (SNPs) modestly influence the risk of developing colorectal cancer. The aim of this study was to test 11 loci, reported to be associated with an increased or decreased risk of colorectal cancer: 8q23.3 (rs16892766), 8q24.21 (rs6983267), 9p24 (rs719725), 10p14 (rs10795668), 11q23.1 (rs3802842), 14q22.2 (rs4444235), 15q13.3 (rs4779584), 16q22.1 (rs9929218), 18q21.1 (rs4939827), 19q13.1 (rs10411210) and 20p12.3 (rs961253), in a Swedish-based cohort.Methods:The cohort was composed of 1786 cases and 1749 controls that were genotyped and analysed statistically. Genotype–phenotype analysis, for all 11 SNPs and sex, age of onset, family history of CRC and tumour location, was performed.Results:Of eleven loci, 5 showed statistically significant odds ratios similar to previously published findings: 8q23.3, 8q24.21, 10p14, 15q13.3 and 18q21.1. The remaining loci 11q23.1, 16q22.1, 19q13.1 and 20p12.3 showed weak trends but somehow similar to what was previously published. The loci 9p24 and 14q22.2 could not be confirmed. We show a higher number of risk alleles in affected individuals compared to controls. Four statistically significant genotype–phenotype associations were found; the G allele of rs6983267 was associated to older age, the G allele of rs1075668 was associated with a younger age and sporadic cases, and the T allele of rs10411210 was associated with younger age.Conclusions:Our study, using a Swedish population, supports most genetic variants published in GWAS. More studies are needed to validate the genotype–phenotype correlations.

Background: The prevalence of major low anterior resection syndrome (LARS) after rectal cancer surgery varies from 17⋅8 to 56⋅0 per cent, but data from high-quality studies are sparse. The aim of this study was to determine the prevalence of LARS and its association with quality of life (QoL) in a large, well defined, population-based cohort. Methods: This was a population-based study that included all patients who had curative rectal cancer surgery with total or partial mesorectal excision in Stockholm County in Sweden between 2007 and 2013. Patients without a remaining stoma, free from cancer and alive in April 2017 were eligible for the study. The LARS score questionnaire, EORTC QLQ-C30 and Cleveland Clinic Florida Fecal Incontinence score were used as outcome measures. Adjusted mean scores (and differences) of EORTC QLQ-C30 for LARS groups were calculated using repeated measures ANCOVA regression models while adjusting for predefined confounders. Results: In total, 481 patients (82⋅6 per cent response rate) were included in the analysis. Mean follow-up time was 6⋅7 (range 3⋅4-11⋅0) years after surgery. The prevalence of LARS was 77⋅4 per cent (370 of 478 patients), with 53⋅1 per cent (254 of 478) experiencing major LARS. Patients with major LARS reported worse on all EORTC QLQ-C30 subscales (except for financial difficulties) than patients without LARS. A higher mean LARS score was associated with a greater impact on bowel-related QoL. Conclusion: After anterior resection for rectal cancer, the majority of patients suffer from major LARS with a negative impact on QoL.