Zaidi Zakaria

Background Colorectal cancer (CRC) is the second most common cancer in men and third in females, a heterogeneous disease involving multistep mechanisms that represents 10% of all cancers globally. This study investigates gene mutation profiling in CRC using Next-Generation sequencing machine. Method Formalin-fixed paraffin-embedded tissues of 30 CRC patients were retrieved and reviewed. DNA was isolated from selected tissues. Desirable quality check using Qubit and Nanoquant machine was done, and desirable libraries prepared were loaded into the sequencer for sequencing. Using Illumina BaseSpace and Illumina Variant interpreter, generated FastQ data were treated for annotation, alignment, and mapping with reference genome. Sequencing-runs with Phred-score ≥ 30 were selected as desirable runs. Finally, the variants were validated on NCBI-dsSNP and Ensembl databases for clinical consequence interpretations. Results Overall, patient distribution consists of 12(40%) females and 18 (60%) males with mean age (53.2 + 5.3). most patients were in TNM stage-3: 53.3% (15/30) and the least was Stage-4: 20%(6/30) respectively. Overall, 73.3%: (22/30) completed the sequencing, and 552 mutations involving 29 genes and 12 chromosomes were detected. The most upregulated variants are KIT:68(12.3%), FGFR4:61(11.1%), EGFR:60(10.9%), ALK:53(9.6%), DCUN1D1:41(7.4%), PDGFR:40(7.2%), KRAS:33(6.0%), CDK4:27(4.9%), FGFR3:26(4.7%), MTOR:14(2.6), while NRAS, CDK6, PIK3CA, and RET each has 13(2.4%) apiece. Chromosomes 4:134/55(24.2%), chr7:84/552(15.2%), chr12:71/552(12.9%), chr5:64/552(11.6%), chr2:61/552(11.1%), chr3:54/552(9.8%), and chr1:43/552(7.8%) are the most involved chromosomes. Nine genes (APC, NRAS, ALK, PIK3CA, KRAS, IDH1, FGFR1, ERBB2, and ESR1) are identified as pathogenic-causing variants in CRC. Conclusion This is the first NGS-based molecular study on FFPE-CRC tissues in hospital-USM that showed the most upregulated variants in CRC and identified nine genes as crucial pathogenic variants.

Obesity is rampantly soaring at an alarming rate globally and simultaneously causing an increased incidence, and predisposition to various comorbidities. obesity is body mass index of >30kg/m2, while <18kg/m2 is underweight. The world at large fails to recognize obesity as an inevitable disease that requires strict measures to control this modifiable risk factor. W.H.O news release reported that over one billion people globally are obese among which 650 million were adults, 340 million were adolescents, and 39 million were children. The lowest obesity prevalence was reported in Timor Leste at 3.80%, Bangladesh at 3.60%, and Vietnam at 2.10% while the highest were noted in Nauru at 61%, cook island at 55.9%, and Palau at 55.3%. obesity is the most prevailing health problem (15% globally) associated with an increased propensity for development of several medical illnesses, obesity-associated adverse outcomes causing fatal complications that are difficult to manage, and premature mortality. The obese often feel they are not socially cared for by society and are accorded limited time by physicians who don’t view their health concerns from their own perspectives. Thus, making them pessimistic from low self-esteem and discrimination, body shaming, and stigmatization. They eventually develop depressive-anxiety disorder because of distrust insight.

Colorectal carcinoma (CRC) is rising exponentially in Asia, representing 11% of cancer worldwide. This study analysed the influence of CRC on patients’ life expectancy (survival and prognosis factors) via clinicopathology data and comorbidity status of CRC patients. Methodology: A retrospective study performed in HUSM using clinical data from the Surgery unit from 2015 to 2020. The demographic and pertinent clinical data were retrieved for preliminary analyses (data cleansing and exploration). Demographics and pathological characteristics were illustrated using descriptive analysis; 5-year survival rates were calculated using Kaplan–Meier methods; potential prognostic variables were analysed using simple and multivariate logistic regression analysis conducted via the Cox proportional hazards model, while the Charlson Comorbidity Scale was used to categorize patients’ disease status. Results: Of a total of 114 CRC patients, two-thirds (89.5%) were from Malay tribes, while Indian and Chinese had 5.3% each. The 50–69.9 years were the most affected group (45.6%). Overall, 40.4% were smokers (majorly male (95.7%)), 14.0% ex-smokers, and 45.6% non-smokers (p-value = 0.001). The Kaplan–Meier overall 5-year median survival time was 62.5%. From the outcomes, patients who were male and >70 years had metastasis present, who presented with per rectal bleeding and were classified as Duke C; and who has tumour in the rectum had the lowest survival rate. Regarding the prognosis factors investigated, “Gender” (adjusted hazard ratio (HR): 2.62; 95% CI: 1.56–7.81, p-value = 0.040), “Presence of metastases” (HR: 3.76; 95% CI: 1.89–7.32, p-value = 0.010), “Metastasis site: Liver” (HR: 5.04; 95% CI: 1.71–19.05, p-value = 0.039), “Lymphovascular permeation” (HR: 2.94; 95% CI: 1.99–5.92, p-value = 0.021), and “CEA-level” (HR: 2.43; 95% CI: 1.49–5.80, p-value = 0.001) remained significant in the final model for multiple Cox proportional hazard regression analyses. There was a significant mean association between tumour grades and the patient’s comorbidity status. Conclusions: Histopathological factors (gender, metastases presence, site of metastases, CEA level, and lymphovascular permeation) showed the best prognosis-predicting factors in CRC.