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.
The rate of local recurrence of rectal cancer (LRRC) has decreased but the condition remains a therapeutic challenge. This study aimed to examine treatment and prognosis in patients with LRRC in Sweden. Special focus was directed towards potential differences between geographical regions and time periods.
All patients with LRRC as first event, following primary surgery for rectal cancer performed during the period 1995-2002, were included in this national population-based cohort-study. Data were collected from the Swedish Colorectal Cancer Registry and from medical records. The cohort was divided into three time periods, based on the date of diagnosis of the LRRC.
In total, 426 patients fulfilled the inclusion criteria. Treatment with curative intent was performed in 149 patients (35%), including 121 patients who had a surgical resection of the LRRC. R0-resection was achieved in 64 patients (53%). Patients with a non-centrally located tumour were more likely to have positive resection margins (R1/R2) (OR 5.02, 95% CI:2.25-11.21). Five-year survival for patients resected with curative intent was 43% after R0-resection and 14% after R1-resection. There were no significant differences in treatment intention or R0-resection rate between time periods or regions. The risk of any failure was significantly higher in R1-resected patients compared with R0-resected patients (HR 2.04, 95% CI:1.22-3.40).
A complete resection of the LRRC is essential for potentially curative treatment. Time period and region had no influence on either margin status or prognosis.
A reduced risk of perforated diverticular disease among individuals with current statin exposure has been reported. The aim of the present study was to investigate whether statins reduce the risk of acute diverticular disease.
A nation-wide population-based case-control study was performed, including 13,127 cases hospitalised during 2006-2010 with a first-time diagnosis of colonic diverticular disease, and 128,442 control subjects (matched for sex, age, county of residence and calendar year). Emergency surgery, assumed to be a proxy for complicated diverticulitis, was performed on 906 of the cases during the index admission, with 8818 matched controls. Statin exposure was classified as "current" or "former" if a statin prescription was last dispensed = 125 days or >125 days before index date, respectively. The association between statin exposure and acute diverticular disease was investigated by conditional logistic regression, including models adjusting for country of birth, educational level, marital status, comorbidities, nonsteroidal anti-inflammatory drug/steroid exposure and healthcare utilisation.
A total of 1959 cases (14.9%) and 16,456 controls (12.8%) were current statin users (crude OR 1.23 [95% CI 1.17-1.30]; fully adjusted OR 1.00 [0.94-1.06]). One hundred and thirty-two of the cases subjected to surgery (14.6%), and 1441 of the corresponding controls (16.3%) were current statin users (crude OR 0.89 [95% CI 0.73-1.08]; fully adjusted OR 0.70 [0.55-0.89]).
The results do not indicate that statins affect the development of symptomatic diverticular disease in general. However, current statin use was associated with a reduced risk of emergency surgery for diverticular disease.