Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
BackgroundThe aim of this research was to study the levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) in tumour tissue samples of colorectal carcinoma based upon immunohistochemical detection and compare those results with patients’ outcome.MethodsTumour blocks of patients surgically treated for colorectal cancer were evaluated by 8-oxodG immunohistochemical staining. The expression was analysed in 500 tumour cells. The percentage of positive cells, as well as staining intensity, was recorded, and Allred score was calculated. For each patient, data of age, gender, tumour size and location, margin status, histologic grade, tumour stage, lymph node status, vascular invasion, overall survival, and therapy protocols were collected. Tumour grade was divided into two groups as low and high grade.ResultsIn this study, 146 consecutive patients with primary colorectal carcinoma were included. All data were available for 138 patients, and they were included in this research. There were 83 male and 55 female patients; the median age was 64 years (range 35–87 years). The results showed shorter 5- and 10-year survival in patients with 8-oxodG positive tumour cells (5-year survival, n = 138, Mantel–Cox, chi-square 4.116, degree of freedom (df) = 1, p < 0.05; 10-year survival, n = 134, Mantel–Cox, chi-square 4.374, df = 1, p < 0.05). The results showed a positive correlation between Allred score and high tumour grade (two-tailed Spearman’s ρ 0.184; p < 0.05), as well as with non-polypoid tumour growth (two-tailed Spearman’s ρ 0.198; p < 0.05). There was no significant difference of 8-oxodG expression related to age, sex, blood group, size and tumour site, distance from the edge of the resected tumour margin, lymph nodes involvement, and vascular invasion.ConclusionsIn this study, the positive correlation between 8-oxodG presence in the tumour cells, worse clinical outcome, higher tumour grade, and flat morphology was found.
BackgroundTwenty common genetic variants have been associated with risk of developing colorectal cancer (CRC) in genome wide association studies to date. Since large differences between populations exist, generalisability of findings to any specific population needs to be confirmed.AimThe aim of this study was to perform an association study between risk variants: rs10795668, rs16892766, rs3802842 and rs4939827 and CRC risk in Croatian population.MethodsAn association study was performed on 320 colorectal cancer cases and 594 controls recruited in Croatia. We genotyped four variants previously associated with CRC: rs10795668, rs16892766, rs3802842 and rs4939827.ResultsSMAD7 variant rs4939827 (18q21.1) was significantly associated with CRC risk in Croatian population. C allele was associated with a decreased risk, odds ratio (OR): 0.70 (95% CI: 0.57-0.85, P=3.5E-04). Compared to TT homozygotes, risk was reduced by 34% in heterozygotes (OR=0.66, 95% CI: 0.47-0.92) and by 52% in CC homozygotes (OR=0.48, 95% CI: 0.33-0.72).ConclusionOur results show association of rs4939827 with colorectal cancer risk in Croatian population. The higher strength of the association in comparison to other studies suggests population-specific environmental or genetic factors may be modifying the association. More studies are needed to further describe role of rs4939827 in CRC. Likely reason for failure of replication for other 3 loci is inadequate study power.
A hernia is an area of weakness or complete disruption of the fibromuscular tissues of the body wall. In addition to the body wall, hernias can occur in the diaphragm, pelvic wall, perineum, pelvic floor, and internal abdominal viscera (hernias through omental or mesenteric defects, ligaments and folds). Surgical repair of different types of hernia is the most common general surgical procedure with more than 20 million hernioplasties performed each year. Abdominal wall hernias are not common during pregnancy. Hernias can be symptomless or have minimal symptoms, including slight discomfort or pain. Such hernias are not life-threatening and should be controlled on regular basis. After spontaneous delivery and uterine involution, they should be repaired on an elective basis. It is of utmost importance for a clinician to diagnose emergent situations, which include incarceration, strangulation and perforation caused by hernia because consultation with a surgeon and emergency operation are mandatory. There is still no consensus for irreducible hernia during pregnancy, but complications during pregnancy outweigh elective operation. Therefore, hernioplasty is recommended during pregnancy, especially in early gestation.
Colorectal cancer (CRC) is one of the most prevalent oncological diseases globally, taking 3 rd place in incidence in the general population. High in mortality, it is also a form of cancer whose outcome is highly dependable on its stage at diagnosis. therefore, many countries have adopted a more or less successful screening process to ensure early diagnosis and, in turn, higher survival rates and better results overall. The COVID-19 pandemic has altered the established medical routines worldwide, with massively postponing diagnostic procedures and elective surgeries. This study aims to measure the effect the pandemic has had on colorectal cancer treatment in our institution. Variables such as deferral time from diagnosis to commencement of treatment, lapse of time between different phases of the treatment process, time of presentation (elective versus emergent surgery), the physical status of the patient at the time of surgery (ASA classification) and metastatic index (positive lymph node ratio), were taken into account. We juxtaposed data from patients treated at the Surgical Department of Clinical Hospital Center in Zagreb in 2019 and 2020, the latter being heavily affected by the pandemic. In 2019 and 2020, 347 and 314 patients, respectively, with c18-c20 diagnoses (International Statistical Classification of Diseases and Related Health Problems ICD-10), have been treated at our Hospital. With exclusion criteria applied, the patient count falls to 173 for 2019 and 157 for 2020. these numbers include operated cases with or without an anastomosis formation and with or without neoadjuvant chemotherapy applied. From the analysis we excluded patients with recurrent colorectal tumors, synchronous and metachronous tumors, and patients treated palliatively. Furthermore, colorectal adenomas were also excluded from the study. Our data shows significant difference between observed variables in the two patient groups, attributed to the COV-iD-19 pandemic. since there is still no reliable way to predict the duration of this global health crisis, it is imperative to implement strategies to lessen the damaging effect the pandemic has had on favourable oncosurgical treatment outcomes in colorectal cancer patients.
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