ABSTRACT
BACKGROUND: Irritable bowel syndrome (IBS) is more common in patients with ulcerative colitis (UC) than expected. The prevalence of IBS in patients with UC with longstanding disease is not known. We investigated the prevalence of IBS-like symptoms in patients with UC in remission and longstanding disease in comparison to control subjects. METHODS: Sixty-eight patients with UC and 33 patients with hereditary familiar colon cancer and who underwent colonoscopy surveillance were included. Faecal calprotectin (FC), Gastrointestinal Symptoms Rating Scale-Irritable Bowel Syndrome (GSRS-IBS) and Hospital Anxiety and Depression scale were fulfilled prior to endoscopy. UC in remission was define by steroid-free clinical remission, a Mayo Score ≤ 1 on endoscopy, a FC ≤ 200 µg/g and no significant active inflammation on colon biopsies. RESULTS: Fifty-five UC patients met the criteria for being in remission. The median disease duration was 17 years. The patients with UC in remission tended to have lower scores on total GSRS-IBS score (6 vs 10.5; p = 0.062) and lower or equal scores on all specific IBS symptoms in comparison to controls. There was a moderate but significant correlation between diarrhoea scores and FC levels (in the span ≤ 200 µg/g) (rs 0.38; p = 0.004) in the UC in remission group. CONCLUSION: Patients with UC with longstanding disease and in remission do not have more IBS symptoms than controls. In UC patients in remission the FC level in the lower span showed a moderate correlation to symptoms of diarrhoea.
Subject(s)
Colitis, Ulcerative/complications , Irritable Bowel Syndrome/epidemiology , Population Surveillance , Adult , Biopsy , Case-Control Studies , Colitis, Ulcerative/pathology , Colitis, Ulcerative/surgery , Colon/pathology , Colonoscopy , Colorectal Neoplasms, Hereditary Nonpolyposis/complications , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , Colorectal Neoplasms, Hereditary Nonpolyposis/surgery , Diarrhea/epidemiology , Diarrhea/etiology , Feces/chemistry , Female , Humans , Irritable Bowel Syndrome/etiology , Leukocyte L1 Antigen Complex/analysis , Male , Middle Aged , Prevalence , Remission, Spontaneous , Severity of Illness Index , Time FactorsABSTRACT
BACKGROUND: Mutations in KRAS, BRAF, PIK3CA and PTEN expression have been in focus to predict the effect of epidermal growth factor receptor-blocking therapy in colorectal cancer (CRC). Here, information on these four aberrations was collected and combined to a Quadruple index and used to evaluate the prognostic role of these factors in CRC. PATIENTS: We analysed the mutation status in KRAS, BRAF and PIK3CA and PTEN expression in two separate CRC cohorts, Northern Sweden Health Disease Study (NSHDS; n=197) and Colorectal Cancer in Umeå Study (CRUMS; n=414). A Quadruple index was created, where Quadruple index positivity specifies cases with any aberration in KRAS, BRAF, PIK3CA or PTEN expression. RESULTS: Quadruple index positive tumours had a worse prognosis, significant in the NSHDS but not in the CRUMS cohort (NSHDS; P=0.003 and CRUMS; P=0.230) in univariate analyses but significance was lost in multivariate analyses. When analysing each gene separately, only BRAF was of prognostic significance in the NSHDS cohort (multivariate HR 2.00, 95% CI: 1.16-3.43) and KRAS was of prognostic significance in the CRUMS cohort (multivariate HR 1.48, 95% CI: 1.02-2.16). Aberrations in PIK3CA and PTEN did not add significant prognostic information. CONCLUSIONS: Our results suggest that establishment of molecular subgroups based on KRAS and BRAF mutation status is important and should be considered in future prognostic studies in CRC.
Subject(s)
Carcinoma/diagnosis , Colorectal Neoplasms/diagnosis , Genes, ras/physiology , PTEN Phosphohydrolase/physiology , Phosphatidylinositol 3-Kinases/physiology , Proto-Oncogene Proteins B-raf/physiology , Adult , Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/physiology , Carcinoma/genetics , Class I Phosphatidylinositol 3-Kinases , Cohort Studies , Colorectal Neoplasms/genetics , DNA Mutational Analysis , Female , Humans , Male , Middle Aged , PTEN Phosphohydrolase/genetics , Phosphatidylinositol 3-Kinases/genetics , Prognosis , Proto-Oncogene Proteins B-raf/geneticsABSTRACT
OBJECTIVE: Polymorphisms in genes involved in folate uptake and metabolism may affect folate status and, thereby, the risk of cancer. In this nested case-referent study, we related two such polymorphisms, reduced folate carrier (RFC1) 80G > A and folate hydrolase 1 (FOLH1) 1561C > T, to the risk of colorectal cancer, taking into account pre-diagnostic plasma folate and total homocysteine concentrations and the MTHFR 677C > T polymorphism, which were analysed in a previous study. MATERIAL AND METHODS: Subjects were 220 cases and 414 matched referents from the population-based Northern Sweden Health and Disease Study. RESULTS: The RFC1 80A-allele was associated with reduced plasma folate and elevated plasma total homocysteine concentrations, but the result was statistically significant only for folate. In contrast, the FOLH1 1561T-allele was associated with higher plasma folate and reduced plasma total homocysteine concentrations, and the result was statistically significant only for homocysteine. Neither polymorphism was related to the risk of colorectal cancer, either in univariate analysis or after adjusting for body mass index, current smoking, recreational and occupational physical activity and alcohol intake. Further adjustment for folate or homocysteine status or the MTHFR 677C > T polymorphism did not affect risk estimates. Subjects with the RFC1 80AA genotype in combination with low plasma folate concentrations or the MTHFR 677TT genotype had a reduced risk of colorectal cancer of borderline statistical significance. CONCLUSIONS: These findings suggest that although the RFC1 80G > A and FOLH1 1561C > T polymorphisms may influence folate status, they are not likely to have a major independent role in the development of colorectal cancer.
