METHOD: Whole-genome sequencing (WGS) was performed in seven early-age-onset Malay CRC patients. Potential germline genetic variants, including single-nucleotide variations and insertions and deletions (indels), were prioritized using functional and predictive algorithms.
RESULTS: An average of 3.2 million single-nucleotide variations (SNVs) and over 800 indels were identified. Three potential candidate variants in three genes-IFNE, PTCH2 and SEMA3D-which were predicted to affect protein function, were identified in three Malay CRC patients. In addition, 19 candidate genes-ANKDD1B, CENPM, CLDN5, MAGEB16, MAP3K14, MOB3C, MS4A12, MUC19, OR2L8, OR51Q1, OR51AR1, PDE4DIP, PKD1L3, PRIM2, PRM3, SEC22B, TPTE, USP29 and ZNF117-harbouring nonsense variants were prioritised. These genes are suggested to play a role in cancer predisposition and to be associated with cancer risk. Pathway enrichment analysis indicated significant enrichment in the olfactory signalling pathway.
CONCLUSION: This study provides a new spectrum of insights into the potential genes, variants and pathways associated with CRC in Malay patients.
METHODS: Histopathological reports of all patients diagnosed with colorectal carcinoma from January 2012 to December 2016 from public hospitals in Sabah were retrieved from the central computerized database of the Pathology Department of Queen Elizabeth Hospital in Kota Kinabalu, Sabah. Supplementary data was obtained from patients' case files from each hospital. Clinico-pathological data were analysed using the IBM SPSS Statistical Software Version 23 for Windows for descriptive statistics (mean, median, ASR, AR, relative risk) and inferential statistics (Chi square test).
RESULTS: A total of 696 patients met the inclusion criteria. The median age for colorectal cancer in Sabah was 62 years (95% CI 60.3 to 62.3), with an age specific incidence rate of 21.4 per 100 000 population. The age specific incidence rate in the indigenous populations was 26.6 per 100 000, much lower than the Chinese, at 65.0 per 100 000. The risk of colorectal cancer occurring before the age of 50 was three times higher in the indigenous population compared to the Chinese. The tumours were mainly left-sided (56.5%), adenocarcinoma in histology (98.4%) and moderately differentiated (88.7%). Approximately 79.2% of patients received curative treatment.
CONCLUSION: Indigenous populations in Sabah develop colorectal cancer at an earlier age, and present at more advanced stages. This has implications for screening and therapeutic strategic planning.
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MATERIALS AND METHODS: The influence of co-culture of myofibroblasts and CRC cell lines is discussed using various in vitro assays including direct co-culture, transwell assays, Matrigel-based differentiation and cell invasion experiments.
RESULTS: The results from these in vitro assays clearly demonstrated various aspects of the crosstalk between myofibroblasts and CRC cell lines, which include cell growth, differentiation, migration and invasion.
CONCLUSION: The reported in vitro assays provide a basis for investigating the factors that control the myofibroblast-epithelial cell interactions in CRC in vivo.
CONCLUSIONS: HMGB1 plays multiple roles in promoting the pathogenesis of colorectal cancer, despite a few contradicting studies. HMGB1 may differentially regulate disease-related processes, depending on the redox status of the protein in colorectal cancer. Binding of HMGB1 to various protein partners may alter the impact of HMGB1 on disease progression. As HMGB1 is heavily implicated in the pathogenesis of colorectal cancer, it is crucial to further improve our understanding of the functional roles of HMGB1 not only in colorectal cancer, but ultimately in all types of cancers.
METHODS: This is a retrospective study examining CRC data for the period 2007 to 2017 retrieved from a population based cancer registry in Brunei Darussalam. A total of 728 patients were included in the analysis. Kaplan Meier method was used to estimate survival rates. Univariate analysis using log-rank test was used to examine the differences in survival between groups. Multivariate analysis using Cox PH regression was used to estimate hazard of death and obtain significant predictors that influence CRC patients' survival.
RESULTS: The median survival time for colorectal, colon and rectal cancer patients were 57.0, 85.8 and 40.0 months respectively. The overall 1-, 3- and 5- year survival rates for CRC patients were 78.0%, 57.7% and 49.6% respectively. In univariate analysis, age at diagnosis, ethnicity, cancer stage, tumour location and histology were found to have significant difference in CRC patients' survival. In the Cox PH analysis, older age (≥70 years), cancer stage, ethnicity and other histological type were determined as associated factors of CRC patients' survival.
CONCLUSION: This study found the overall 5-year survival rate of CRC in Brunei Darussalam is similar to that in some Asian countries such as Singapore and Malaysia. However, more efforts need to be carried out in order to raise awareness of CRC and improve the survival of CRC patients.
PATIENTS AND METHODS: We compared a prospectively collected group of 48 patients undergoing oxaliplatin/irinotecan-based perioperative systemic chemotherapy (s-CT) with targeted agents, and cytoreductive surgery (CRS) (no-HIPEC group) with 48 controls undergoing the same perioperative s-CT and CRS/HIPEC (HIPEC group). Patients were matched (1:1) according to the Peritoneal Surface Disease Severity Score, completeness of cytoreduction, history of extraperitoneal disease (EPD), and Peritoneal Cancer Index.
RESULTS: The groups were comparable, except for a higher number of patients in the HIPEC group with World Health Organization performance status 0, pN2 stage primary tumor, and treated with preoperative s-CT. Forty-one patients in the no-HIPEC group and 43 patients in the HIPEC group had optimal comprehensive treatment (P = 0.759), defined as complete cytoreduction of PM and margin-negative EPD resection. Median follow-up was 31.6 months in the no-HIPEC group and 39.9 months in the HIPEC group. Median overall survival was 39.3 months in the no-HIPEC group and 34.8 months in the HIPEC group (P = 0.702). In the two groups, severe morbidity occurred in 14 (29.2%) and 13 (27.1%) patients, respectively (P = 1.000), with no operative deaths. On multivariate analysis, left-sided primary and curative treatment independently correlated with better survival while HIPEC did not (hazard ratio 0.73; 95% confidence interval 0.47-1.15; P = 0.178).
CONCLUSIONS: Our results confirmed that, in selected patients, perioperative s-CT and surgical treatment of CRC-PM resulted in unexpectedly high survival rates. Mitomycin C-based HIPEC did not increase morbidity but did not impact prognosis.
METHODS: We applied a multiplex serology assay to simultaneously measure antibody responses to 11 F. nucleatum antigens in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI).
RESULTS: We observed neither a statistically significant colorectal cancer risk association for antibodies to individual F. nucleatum proteins nor for combined positivity to any of the 11 proteins (OR, 0.81; 95% CI, 0.62-1.06).
CONCLUSIONS: Antibody responses to F. nucleatum proteins in prediagnostic serum samples from a subset of colorectal cancer cases and matched controls within the EPIC study were not associated with colorectal cancer risk.
IMPACT: Our findings in prospectively ascertained serum samples contradict the existing literature on the association of F. nucleatum with colorectal cancer risk. Future prospective studies, specifically detecting F. nucleatum in stool or tissue biopsies, are needed to complement our findings.