The genetic susceptibility to colorectal cancer (CRC) has been estimated to be around 35% and yet high-penetrance germline mutations found so far explain less than 5% of all cases. Much of the remaining variations could be due to the co-inheritance of multiple low penetrant variants. The identification of all the susceptibility alleles could have public health relevance in the near future. To test the hypothesis that what are considered polymorphisms in human CRC genes could constitute low-risk alleles, we selected eight common SNPs for a pilot association study in 1785 cases and 1722 controls. One SNP, rs3219489:G>C (MUTYH Q324H) seemed to confer an increased risk of rectal cancer in homozygous status (OR=1.52; CI=1.06-2.17). When the analysis was restricted to our 'super-controls', healthy individuals with no family history for cancer, also rs1799977:A>G (MLH1 I219V) was associated with an increased risk in both colon and rectum patients with an odds ratio of 1.28 (CI=1.02-1.60) and 1.34 (CI=1.05-1.72), respectively (under the dominant model); while 2 SNPs, rs1800932:A>G (MSH6 P92P) and rs459552:T>A (APC D1822V) seemed to confer a protective effect. The latter, in particular showed an odds ratio of 0.76 (CI=0.60-0.97) among colon patients and 0.73 (CI=0.56-0.95) among rectal patients. In conclusion, our study suggests that common variants in human CRC genes could constitute low-risk alleles.
OBJECTIVES: This study aimed to validate the accuracy of data retrieved in a prospective multicenter trial, the purpose of which was an economic evaluation of two techniques of surgery for colon cancer. METHODS: Within the Swedish contribution of the COLOR trial (Colon Cancer Open or Laparoscopic Resection), an economic evaluation of open versus laparoscopic surgical techniques was conducted. Data were collected by case record forms (CRF), patient diaries, and telephone surveys every 2 weeks. The study period was 12 weeks, and the perspective was societal. Data from the first consecutive forty patients to complete the health economic study protocol were validated. Retrieved data were compared with data from medical records and data from local social security offices for agreement. RESULTS: Statistically significant differences were found for duration of anesthesia, length of surgery, number of outpatient consultations by doctors and district nurses, complication rate, and the use of central venous lines. No significant differences were observed concerning length of hospital stay, disposable instruments cost, and time off work, all of which heavily influence total costs. CONCLUSIONS: The present method of data collection regarding resources used in this setting seems to produce accurate data for economic evaluation; however, relative to complication rates, the method did not retrieve accurate data.
Human polymorphisms affecting gut epithelial barrier and interactions with bacteria predispose to the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC). The intestinal transporter PepT1, encoded by the SLC15A1 gene, mediates intracellular uptake of bacterial products that can induce inflammation and NF-kappaB activation upon binding to NOD2, a protein often mutated in CD. Hence, we tested SLC15A1 polymorphisms for association with IBD.
Twelve SLC15A1 single nucleotide polymorphisms (SNPs) were genotyped in 1783 individuals from 2 cohorts of Swedish and Finnish IBD patients and controls. An in vitro system was set up to evaluate the potential impact of SLC15A1 polymorphism on PepT1 transporter function by quantification of NOD2-mediated activation of NF-kappaB.
The common allele (C) of a coding polymorphism (rs2297322, Ser117Asn) was associated with CD susceptibility both in Sweden and in Finland, but with genetic effects in opposite directions (risk and protection, respectively). The best evidence of association was found in both populations when the analysis was performed on individuals not carrying NOD2 common risk alleles (Sweden allelic P = 0.0007, OR 1.97, 95% confidence interval [CI] 1.34-2.92; Finland genotype P = 0.0013, OR 0.63, 95% CI 0.44-0.90). The PepT1 variant encoded by the C allele (PepT1-Ser117) was associated with reduced signaling downstream of NOD2 (P
In this population-based study, the aim was to investigate risk factors for lymph node metastases and to construct a risk stratification index with relevance for pre-operative planning in T1 and T2 rectal cancers.
Data were retrieved from The Swedish Rectal Cancer Register, a mandatory, national, prospectively collected data base. All T1 and T2 rectal cancers treated with abdominal resection surgery without neo-adjuvant or adjuvant radio-chemotherapy from 2007 to 2010 were analysed. T-stage, sm-level, histologic differentiation, mucinous tumour type, blood vessel- and perineural infiltration, tumour location (in cm from the anal verge), age and gender were evaluated as potential predictors of lymph node metastases, using uni- and multivariate logistic regression.
T2-stage (odds ratio [OR]=2.0), poor differentiation (OR=6.5) and vascular infiltration (OR=4.3) were identified as significant risk-factors for lymph node metastases in the multivariate analysis. The risk stratification index shows the risk for lymph node metastases gradually increasing from 6% to 65% and 11% to 78% in T1 and T2 cancers respectively, when adding the risk factors one by one.
There is a considerable span in the risk for lymph node metastases between low risk T1 and high risk T2 rectal cancer. Using the risk stratification-model, with the concept of local excision as a macro-biopsy with standby for subsequent immediate radical resection surgery in high-risk cases, could benefit patients by providing the advantages of local excision yet ensuring adequate oncologic outcome.