Annals of gastroenterology : quarterly publication of the Hellenic Society of Gastroenterology, 2012
Inflammatory bowel diseases (IBD) are associated to an increased risk of colorectal cancer, which... more Inflammatory bowel diseases (IBD) are associated to an increased risk of colorectal cancer, which is primarily related to long-standing chronic inflammation. Recognized risk factors are the duration and extent of the disease, severe endoscopic and histological inflammation, primary sclerosing cholangitis, family history of colorectal cancer and in some studies young age at diagnosis. Recent population-based studies have shown that the risk is lower than previously described or even similar to that of the general population, and this could be justified by methodological aspects (hospital-based vs. population-based studies) or by a true decrease in the risk related to a better control of the disease, the use of drugs with chemoprotective effect or the spread of endoscopic surveillance in high-risk patients. Apart from colorectal cancer, patients with IBD are prone to other intestinal neoplasms (lymphoma, small bowel adenocarcinoma, pouch neoplasia and perianal neoplasia). In this arti...
Background Colorectal cancer (CRC) is a disease of complex aetiology, with much of the expected i... more Background Colorectal cancer (CRC) is a disease of complex aetiology, with much of the expected inherited risk being due to several common low risk variants. Genome-Wide Association Studies (GWAS) have identified 20 CRC risk variants. Nevertheless, these have only been able to explain part of the missing heritability. Moreover, these signals have only been inspected in populations of Northern European origin. Results Thus, we followed the same approach in a Spanish cohort of 881 cases and 667 controls. Sixty-four variants at 24 loci were found to be associated with CRC at p-values <10-5. We therefore evaluated the 24 loci in another Spanish replication cohort (1481 cases and 1850 controls). Two of these SNPs, rs12080929 at 1p33 (Preplication=0.042; Ppooled=5.523x10-03; OR (CI95%)=0.866(0.782-0.959)) and rs11987193 at 8p12 (Preplication=0.039; Ppooled=6.985x10-5; OR (CI95%)=0.786(0.705-0.878)) were replicated in the second Phase, although they did not reach genome-wide statistical...
... Department of Gastroenterology, University Hospital Maastricht, The Netherlands; On behalf of... more ... Department of Gastroenterology, University Hospital Maastricht, The Netherlands; On behalf of the EC-IBD Study Group. ,; Marieke Pierik: Affiliations. ... Affiliations. Department of Gastroenterology, University Hospital of Heraklion, Greece; On behalf of the EC-IBD Study Group. ...
Background Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized b... more Background Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala) variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS. Methods The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls)....
Annals of gastroenterology : quarterly publication of the Hellenic Society of Gastroenterology, 2012
Inflammatory bowel diseases (IBD) are associated to an increased risk of colorectal cancer, which... more Inflammatory bowel diseases (IBD) are associated to an increased risk of colorectal cancer, which is primarily related to long-standing chronic inflammation. Recognized risk factors are the duration and extent of the disease, severe endoscopic and histological inflammation, primary sclerosing cholangitis, family history of colorectal cancer and in some studies young age at diagnosis. Recent population-based studies have shown that the risk is lower than previously described or even similar to that of the general population, and this could be justified by methodological aspects (hospital-based vs. population-based studies) or by a true decrease in the risk related to a better control of the disease, the use of drugs with chemoprotective effect or the spread of endoscopic surveillance in high-risk patients. Apart from colorectal cancer, patients with IBD are prone to other intestinal neoplasms (lymphoma, small bowel adenocarcinoma, pouch neoplasia and perianal neoplasia). In this arti...
Background Colorectal cancer (CRC) is a disease of complex aetiology, with much of the expected i... more Background Colorectal cancer (CRC) is a disease of complex aetiology, with much of the expected inherited risk being due to several common low risk variants. Genome-Wide Association Studies (GWAS) have identified 20 CRC risk variants. Nevertheless, these have only been able to explain part of the missing heritability. Moreover, these signals have only been inspected in populations of Northern European origin. Results Thus, we followed the same approach in a Spanish cohort of 881 cases and 667 controls. Sixty-four variants at 24 loci were found to be associated with CRC at p-values <10-5. We therefore evaluated the 24 loci in another Spanish replication cohort (1481 cases and 1850 controls). Two of these SNPs, rs12080929 at 1p33 (Preplication=0.042; Ppooled=5.523x10-03; OR (CI95%)=0.866(0.782-0.959)) and rs11987193 at 8p12 (Preplication=0.039; Ppooled=6.985x10-5; OR (CI95%)=0.786(0.705-0.878)) were replicated in the second Phase, although they did not reach genome-wide statistical...
... Department of Gastroenterology, University Hospital Maastricht, The Netherlands; On behalf of... more ... Department of Gastroenterology, University Hospital Maastricht, The Netherlands; On behalf of the EC-IBD Study Group. ,; Marieke Pierik: Affiliations. ... Affiliations. Department of Gastroenterology, University Hospital of Heraklion, Greece; On behalf of the EC-IBD Study Group. ...
Background Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized b... more Background Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala) variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS. Methods The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls)....
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