scholarly journals Cyclin D1 Polymorphism and Increased Risk of Colorectal Cancer at Young Age

2001 ◽  
Vol 93 (14) ◽  
pp. 1106-1108 ◽  
Author(s):  
S. Kong ◽  
Q. Wei ◽  
C. I. Amos ◽  
P. M. Lynch ◽  
B. Levin ◽  
...  
2007 ◽  
Vol 10 (2) ◽  
pp. 29-36
Author(s):  
T Josifovski ◽  
N Matevska ◽  
M Hiljadnikova-Bajro ◽  
Z Sterjev ◽  
A Kapedanovska ◽  
...  

Cyclin D1 G870A Variant is Associated with Increased Risk of Microsatellite Instability-Positive Colorectal Cancer in Young Male PatientsCyclin D1 (CCND1) is a cell cycle regulatory protein, which is often over expressed in human tumors and is associated with cell proliferation and poor prognosis. A common G870A single nucleotide polymorphism at codon 242 in exon 4 of the CCND1 gene is associated with an altered messenger RNA transcript and increased risk of colorectal cancer (CRC) and adenoma in some studies. Over expression of CCND1 modifies the effect of mutations in mismatch repair (MMR) genes, enhances microsatellite instability (MSI), and influences the age ofonset of hereditary non polyposis colorectal cancer (HNPCC). We have extended our study that indicated that the CCND1 A variant may influence the age of onset of CRC in the Macedonian population only in patients who exhibit MSI tumors by a case control study of 331 randomly selected CRC patients and 101 controls without clinical diagnosis of CRC. We did not observe a significant difference in overall allelic frequencies and genotype distribution of affected and unaffected mutation carriers, but found a statistically significant risk of CRC in carriers of the CCND1 A allele when patients were grouped according to gender, age and MSI status. A higher risk was observed in patients with MSI-positive tumors and particularly in male patients under 60 years of age. The consequences of the above observation were reversed in female patients. These results indicate that the CCND1 A variant may enhance CRC progression through a pathway influenced by estrogens in colonic epithelia.


2005 ◽  
Vol 41 (7) ◽  
pp. 1037-1044 ◽  
Author(s):  
Yi Hong ◽  
Kong Weng Eu ◽  
Francis Seow-Choen ◽  
Stephanie Fook-Chong ◽  
Peh Yean Cheah

2019 ◽  
Vol 56 (6) ◽  
pp. 370-379 ◽  
Author(s):  
Winifred Lo ◽  
Bin Zhu ◽  
Arvind Sabesan ◽  
Ho-Hsiang Wu ◽  
Astin Powers ◽  
...  

IntroductionHereditary diffuse gastric cancer (HDGC) is a cancer syndrome associated with variants in E-cadherin (CDH1), diffuse gastric cancer and lobular breast cancer. There is considerable heterogeneity in its clinical manifestations. This study aimed to determine associations between CDH1 germline variant status and clinical phenotypes of HDGC.MethodsOne hundred and fifty-two HDGC families, including six previously unreported families, were identified. CDH1 gene-specific guidelines released by the Clinical Genome Resource (ClinGen) CDH1 Variant Curation Expert Panel were applied for pathogenicity classification of truncating, missense and splice site CDH1 germline variants. We evaluated ORs between location of truncating variants of CDH1 and incidence of colorectal cancer, breast cancer and cancer at young age (gastric cancer at <40 or breast cancer <50 years of age).ResultsFrequency of truncating germline CDH1 variants varied across functional domains of the E-cadherin receptor gene and was highest in linker (0.05785 counts/base pair; p=0.0111) and PRE regions (0.10000; p=0.0059). Families with truncating CDH1 germline variants located in the PRE-PRO region were six times more likely to have family members affected by colorectal cancer (OR 6.20, 95% CI 1.79 to 21.48; p=0.004) compared with germline variants in other regions. Variants in the intracellular E-cadherin region were protective for cancer at young age (OR 0.2, 95% CI 0.06 to 0.64; p=0.0071) and in the linker regions for breast cancer (OR 0.35, 95% CI 0.12 to 0.99; p=0.0493). Different CDH1 genotypes were associated with different intracellular signalling activation levels including different p-ERK, p-mTOR and β-catenin levels in early submucosal T1a lesions of HDGC families with different CDH1 variants.ConclusionType and location of CDH1 germline variants may help to identify families at increased risk for concomitant cancers that might benefit from individualised surveillance and intervention strategies.


2014 ◽  
Vol 146 (5) ◽  
pp. S-408
Author(s):  
Yezaz A. Ghouri ◽  
Sachin Batra ◽  
Nirav C. Thosani ◽  
Sushovan Guha

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 407
Author(s):  
Reetta Holma ◽  
Reijo Laatikainen ◽  
Helena Orell ◽  
Heikki Joensuu ◽  
Katri Peuhkuri ◽  
...  

Chemotherapy-induced mucosal injury of the small intestine may interfere with the enzymes and transporters responsible for the hydrolysis and absorption of dietary carbohydrates causing diarrhoea, abdominal discomfort and pain. The aim of this study was to investigate the association between the consumption of foods rich in FODMAPs (fermentable oligo-, di- and monosaccharides and polyols) and gastrointestinal symptoms in patients receiving adjuvant therapy for colorectal cancer. The patients (n = 52) filled in a 4-day food diary at baseline and during therapy and kept a symptom diary. The intakes of FODMAP-rich foods were calculated as portions and the intakes were divided into two consumption categories. Patients with high consumption of FODMAP-rich foods had diarrhoea more frequently than those with low consumption (for lactose-rich foods the odds ratio (OR) was 2.63, P = 0.03; and for other FODMAP-rich foods 1.82, P = 0.20). Patients with high consumption of both lactose-rich and other FODMAP-rich foods had an over 4-fold risk of developing diarrhoea as compared to those with low consumption of both (OR, 4.18; P = 0.02). These results were confirmed in multivariate models. Conclusion: Consumption of lactose-rich foods results in an increased risk of diarrhoea during adjuvant therapy for colorectal cancer, especially when the consumption of other FODMAP-rich foods is also high.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A38-A38
Author(s):  
Shilpa Ravindran ◽  
Heba Sidahmed ◽  
Harshitha Manjunath ◽  
Rebecca Mathew ◽  
Tanwir Habib ◽  
...  

BackgroundPatients with inflammatory bowel disease (IBD) have increased risk of developing colorectal cancer (CRC), depending on the duration and severity of the disease. The evolutionary process in IBD is driven by chronic inflammation leading to epithelial-to-mesenchymal transition (EMT) events in colonic fibrotic areas. EMT plays a determinant role in tumor formation and progression, through the acquisition of ‘stemness’ properties and the generation of neoplastic cells. The aim of this study is to monitor EMT/cancer initiating tracts in IBD in association with the deep characterization of inflammation in order to assess the mechanisms of IBD severity and progression towards malignancy.Methods10 pediatric and 20 adult IBD patients, admitted at Sidra Medicine (SM) and Hamad Medical Corporation (HMC) respectively, have been enrolled in this study, from whom gut tissue biopsies (from both left and right side) were collected. Retrospectively collected tissues (N=10) from patients with malignancy and history of IBD were included in the study. DNA and RNA were extracted from fresh small size (2–4 mm in diameter) gut tissues using the BioMasher II (Kimble) and All Prep DNA/RNA kits (Qiagen). MicroRNA (miRNA; N=700) and gene expression (N=800) profiling have been performed (cCounter platform; Nanostring) as well as the methylation profiling microarray (Infinium Methylation Epic Bead Chip kit, Illumina) to interrogate up to 850,000 methylation sites across the genome.ResultsDifferential miRNA profile (N=27 miRNA; p<0.05) was found by the comparison of tissues from pediatric and adult patients. These miRNAs regulate: i. oxidative stress damage (e.g., miR 99b), ii. hypoxia induced autophagy; iii. genes associated with the susceptibility to IBD (ATG16L1, NOD2, IRGM), iv. immune responses, such as TH17 T cell subset (miR 29). N=6 miRNAs (miR135b, 10a196b, 125b, let7c, 375) linked with the regulation of Wnt/b-catenin, EM-transaction, autophagy, oxidative stress and play role also in cell proliferation and mobilization and colorectal cancer development were differentially expressed (p<0.05) in tissues from left and right sides of gut. Gene expression signature, including genes associated with inflammation, stemness and fibrosis, has also been performed for the IBD tissues mentioned above. Methylation sites at single nucleotide resolution have been analyzed.ConclusionsAlthough the results warrant further investigation, differential genomic profiling suggestive of altered pathways involved in oxidative stress, EMT, and of the possible stemness signature was found. The integration of data from multiple platforms will provide insights of the overall molecular determinants in IBD patients along with the evolution of the disease.Ethics ApprovalThis study was approved by Sidra Medicine and Hamad Medical Corporation Ethics Boards; approval number 180402817 and MRC-02-18-096, respectively.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Weber ◽  
D.W Biery ◽  
A Singh ◽  
S Divakaran ◽  
A.N Berman ◽  
...  

Abstract Background Autoimmune systemic inflammatory diseases are associated with an increased risk of cardiovascular disease, particularly myocardial infarction (MI). However, there are limited data on the prevalence and effects of inflammatory disease among U.S. adults who experience an MI at a young age. Purpose We sought to determine the prevalence and prognostic value of inflammatory disease in U.S. adults who experience an MI at a young age. Methods The YOUNG-MI registry is a retrospective cohort study of consecutive patients who experienced a Type 1 MI at or below the age of 50 years from 2000 to 2016 at two large medical centers. A diagnosis of rheumatoid arthritis (RA), psoriasis (PsO), systemic lupus erythematosus (SLE), or inflammatory arthritis was determined through physician review of electronic medical records (EMR). Demographic information, presence of cardiovascular (CV) risk-factors, medical procedures, and medications upon discharge were also ascertained from the EMR. Incidence of death was determined using a combination of EMR and national databases. Cox proportional hazard modeling was performed on a sub-sample following Mahalanobis Distance matching on age, sex, and CV risk factors. Results The cohort consisted of 2097 individuals (median age 45 years, 19% female, 53% ST-elevation MI). Among these, 53 (2.5%) individuals possessed a diagnosis of systemic inflammatory disease at or before their index MI (23% SLE, 9% RA, 64% PsO, 4% inflammatory arthritis). When compared to the remainder of the cohort, patients with a diagnosis of systemic inflammatory disease were more likely to be female (36% vs 19%, p=0.004) and be diagnosed with hypertension (62% vs 46%, p=0.025). There was, however, no significant difference in the prevalence of other CV risk factors – diabetes, smoking, dyslipidemia – or a family history of premature coronary artery disease. Despite these similarities, patients with inflammatory disease were less likely to be prescribed aspirin (88% vs 95%, p=0.049) or a statin (76% vs 89%, p=0.008) upon discharge. Over a median follow-up of 11.2 years, patients with inflammatory disease experienced an increased risk of all-cause mortality when compared with the full-cohort (Figure). Compared to the matched sample (n=138), patients with systemic inflammatory disease exhibited an increased risk of all-cause mortality (HR=2.68, CI [1.18 to 6.07], p=0.018), which remained significant after multivariable adjustment for length of stay and GFR (HR=2.38, CI [1.02 to 5.54], p=0.045). Conclusions Among individuals who experienced an MI at a young age, approximately 2.5% had evidence of a systemic inflammatory disease at or before their MI. When compared with a population of individuals with similar cardiovascular risk profiles, those with inflammatory disease had higher rates of all-cause mortality. Our findings suggest that the presence of a systemic inflammatory disorder is independently associated with worse long-term outcomes. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): 1. 5T32 HL094301 NIH T32 Training Grant, “Noninvasive Cardiovascular Imaging Research Training Program”


Author(s):  
Petrus Boström ◽  
Johan Svensson ◽  
Camilla Brorsson ◽  
Martin Rutegård

Abstract Purpose Even though anastomotic leakage after colorectal surgery is a major clinical problem in need of a timely diagnosis, early indicators of leakage have been insufficiently studied. We therefore conducted a population-based observational study to determine whether the patient’s early postoperative pain is an independent marker of anastomotic leakage. Methods By combining the Swedish Colorectal Cancer Registry and the Swedish Perioperative Registry, we retrieved prospectively collected data on 3084 patients who underwent anastomotic colorectal surgery for cancer in 2014–2017. Postoperative pain, measured with the numerical rating scale (NRS), was considered exposure, while anastomotic leakage and reoperation due to leakage were outcomes. We performed logistic regression to evaluate associations, estimating odds ratios (ORs) and 95% confidence intervals (CIs), while multiple imputation was used to handle missing data. Results In total, 189 patients suffered from anastomotic leakage, of whom 121 patients also needed a reoperation due to leakage. Moderate or severe postoperative pain (NRS 4–10) was associated with an increased risk of anastomotic leakage (OR 1.69, 95% CI 1.21–2.38), as well as reoperation (OR 2.17, 95% CI 1.41–3.32). Severe pain (NRS 8–10) was more strongly related to leakage (OR 2.38, 95% CI 1.44–3.93). These associations were confirmed in multivariable analyses and when reoperation due to leakage was used as an outcome. Conclusion In this population-based retrospective study on prospectively collected data, increased pain in the post-anaesthesia care unit is an independent marker of anastomotic leakage, possibly indicating a need for further diagnostic measures.


Author(s):  
Caroline J. Chapman ◽  
Ayan Banerjea ◽  
David J Humes ◽  
Jaren Allen ◽  
Simon Oliver ◽  
...  

AbstractObjectivesCurrently, NICE recommends the use of faecal immunochemical test (FIT) at faecal haemoglobin concentrations (f-Hb) of 10 μg Hb/g faeces to stratify for colorectal cancer (CRC) risk in symptomatic populations. This f-Hb cut-off is advised across all analysers, despite the fact that a direct comparison of analyser performance, in a clinical setting, has not been performed.MethodsTwo specimen collection devices (OC-Sensor, OC-S; HM-JACKarc, HM-J) were sent to 914 consecutive individuals referred for follow up due to their increased risk of CRC. Agreement of f-Hb around cut-offs of 4, 10 and 150 µg Hb/g faeces and CRC detection rates were assessed. Two OC-S devices were sent to a further 114 individuals, for within test comparisons.ResultsA total of 732 (80.1%) individuals correctly completed and returned two different FIT devices, with 38 (5.2%) CRCs detected. Median f-Hb for individuals diagnosed with and without CRC were 258.5 and 1.8 µg Hb/g faeces for OC-S and 318.1 and 1.0 µg Hb/g faeces for HM-J respectively. Correlation of f-Hb results between OC-S/HM-J over the full range was rho=0.74, p<0.001. Using a f-Hb of 4 µg Hb/g faeces for both tests found an agreement of 88.1%, at 10 µg Hb/g faeces 91.7% and at 150 µg Hb/g faeces 96.3%. A total of 114 individuals completed and returned two OC-S devices; correlation across the full range was rho=0.98, p<0.001.ConclusionsWe found large variations in f-Hb when different FIT devices were used, but a smaller variation when the same FIT device was used. Our data suggest that analyser-specific f-Hb cut-offs are applied with regard to clinical decision making, especially at lower f-Hb.


2021 ◽  
Vol 10 (14) ◽  
pp. 3127
Author(s):  
Szu-Chia Liao ◽  
Hong-Zen Yeh ◽  
Chi-Sen Chang ◽  
Wei-Chih Chen ◽  
Chih-Hsin Muo ◽  
...  

We conducted a retrospective cohort study to evaluate the subsequent colorectal cancer (CRC) risk for women with gynecologic malignancy using insurance claims data of Taiwan. We identified patients who survived cervical cancer (N = 25,370), endometrial cancer (N = 8149) and ovarian cancer (N = 7933) newly diagnosed from 1998 to 2010, and randomly selected comparisons (N = 165,808) without cancer, matched by age and diagnosis date. By the end of 2011, the incidence and hazard ratio (HR) of CRC were estimated. We found that CRC incidence rates were 1.26-, 2.20-, and 1.61-fold higher in women with cervical, endometrial and ovarian cancers, respectively, than in comparisons (1.09/1000 person–years). The CRC incidence increased with age. Higher adjusted HRs of CRC appeared within 3 years for women with endometrial and ovarian cancers, but not until the 4th to 7th years of follow up for cervical cancer survivals. Cancer treatments could reduce CRC risks, but not significantly. However, ovarian cancer patients receiving surgery alone had an incidence of 3.33/1000 person–years for CRC with an adjusted HR of 3.79 (95% CI 1.11–12.9) compared to patients without any treatment. In conclusion, gynecologic cancer patients are at an increased risk of developing CRC, sooner for those with endometrial or ovarian cancer than those with cervical cancer.


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