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A hybrid enzymatic zinc-air fuel cell

Abdul Aziz Ahmad, Raihan Othman, Faridah Yusof, Mohd Firdaus Abdul Wahab

Sains Malaysiana, 2014;43:459-465.

A hybrid biofuel cell, a zinc-air cell employing laccase as the oxygen reduction catalyst is investigated. A simple cell design is employed; a membraneless single chamber and a freely suspended laccase in the buffer electrolyte. The cell is characterised based on its open-circuit voltage, power density profile and galvanostatic discharge at 0.5 mA. The activity of laccase as an oxidoreductase is substantiated from the cell discharge profiles. The use of air electrode in the cell design enhanced the energy output by 14%. The zinc-air biofuel cell registered an open-circuit voltage of 1.2 V and is capable to deliver a maximum power density of 1.1 mWcm-2 at 0.4 V. Despite its simple design features, the power output is comparable to that of biocatalytic cell utilising a much more complex system design.
Fulltext Functional diversity of biocatalysts: whether to bioprospect or bioengineer?

Benbelgacem, Farah Fadwa, Bellag, Oualid Abdelkader, Soroodi, Fatemeh, Abdul Aziz Ahmad, Hamzah Mohd Salleh, Noorbatcha, Ibrahim Ali

Biological and Natural Resources Engineering Journal, 2019;2(1):64-84.
MyJurnal

Biocatalyst should have sufficient and efficient activity for the intended
biotechnological application. In the quest for novel biocatalyst, there is a need to have a
genetic diversity either by finding it within the astronomically large number of possible
candidates or to obtain it by bioengineering an existing gene supported by various
bioinformatic and molecular engineering tools. Nowadays, it is well-known that a huge
number of microorganisms is unculturable and poses great challenges to access biocatalysts
from these microbes. Metagenomics is one of the methods widely applied to reach out
maximum possible variants to “bioprospect” biocatalysts. On the other hand, other approaches
are available to bioengineer enzymes by modifying the DNA sequence precisely based on the
structure and the function information of the protein in the case of rational design, or by a
brave creation of anarchic mutations of the DNA sequence with directed evolution method. In
this regard, both approaches, whether to bioprospect or to bioengineer biocatalysts have
advantages and disadvantages which will be discussed in this paper.KEY WORDS: Sugar
industry wastewater; aluminium sulphate; primary treatment, ferric chloride; polyaluminium
chloride
Fulltext The Clinical Profile of Unilateral and Bilateral Optic Disc Swelling in a Tertiary Center in Northern Malaysia

Abdul Aziz AM, Ismail AS, Yaakub A

Cureus, 2022 Oct;14(10):e30572.
PMID: 36415408 DOI: 10.7759/cureus.30572

Background Optic disc swelling (ODS) is a pathological condition with a variety of causes, including optic neuritis (ON), anterior ischemic optic neuropathy, and papilledema. Determining the causes of ODS is critical due to the possibilities of vision- or life-threatening diseases, such as space-occupying lesions. This study aimed to investigate the clinical profile of unilateral and bilateral ODS in Penang Hospital, Malaysia. Methodology This retrospective, descriptive study was conducted in Penang Hospital. Medical records of patients who were diagnosed with ODS from June 2018 until June 2020 in Penang Hospital Eye Emergency Clinic were reviewed. We excluded patients who defaulted on subsequent three months of follow up and those with pseudo-ODS. Results ODS was diagnosed in 43 patients who were all included in the study. Majority were females 55.8% (n = 24), with age ranging from 16 to 78 years. ON contributed most (41.9%, n = 18), followed by non-arteritic anterior ischemic optic neuropathy (NA-AION) (34.9%, n = 15), and papilledema (9.3%, n = 4). Other causes (14%, n = 6) included diabetic papillitis (n = 1), hypertensive retinopathy (n = 1), and central retinal vein occlusion (n = 4). Poor mean initial visual acuity was seen in patients with ON (1.07 ± 0.68) and NA-AION (1.33 ± 0.67). ON showed better final visual outcomes compared to NA-AION at the one-year follow-up. Conclusions ON and NA-AION were identified as the two most common causes of ODS in Penang Hospital for both unilateral and bilateral presentations. Most cases presented with poor initial visual acuity. After one year of follow-up, good visual recovery was seen in ON cases compared to other cases. These results were comparable with studies conducted in other Asian counties.
Fulltext Clinicopathological and Prognostic Characteristics of Malaysian Triple Negative Breast Cancer Patients Undergoing TAC Chemotherapy Regimen

Abdul Aziz AA, Md Salleh MS, Ankathil R

Int J Breast Cancer, 2020;2020:8424365.
PMID: 32308997 DOI: 10.1155/2020/8424365

Triple negative breast cancer (TNBC) is associated with aggressive tumour phenotype and early tumour relapse following diagnosis. Generally, clinicopathological features such as tumour size, patient's age at diagnosis, tumour histology subtypes, grade and stage, involvement of lymph nodes, and menopausal status are commonly used for predicting disease progression, prospects of recurrence, and treatment response. Prognostic value of clinicopathological features on Malaysian TNBC patients is limited. Thus, this study is aimed at investigating the association of clinicopathological features on disease-free survival (DFS) and overall survival (OS) of Malaysian TNBC patients undergoing TAC chemotherapy. Seventy-six (76) immunohistochemistry-confirmed TNBC patients were recruited. The clinicopathological features of TNBC patients were collected and recorded. Kaplan-Meier and log-rank followed by a Cox proportional hazard regression model were performed to evaluate the TNBC patients' survival. Out of 76 TNBC patients, 25 were chemoresistant and 51 were chemoresponders to the TAC chemotherapy regimen. The overall 5-year cumulative DFS and OS of TNBC patients were 63.5% and 76.3%, respectively. Multivariate Cox analysis demonstrated that medullary and metaplastic histology subtypes and positive axillary lymph node metastasis were significant prognostic factors associated with relapse with adjusted HR: 5.76, 95% CI: 2.35, 14.08 and adjusted HR: 3.55, 95% CI: 1.44, 8.74, respectively. Moreover, TNBC patients with medullary and metaplastic histology subtypes and positive axillary lymph node metastases had a higher risk to death than patients who had infiltrating ductal carcinoma and negative axillary lymph node metastasis (adjusted HR: 8.30, 95% CI: 2.38, 28.96 and adjusted HR: 6.12, 95% CI: 1.32, 28.42, respectively). Our results demonstrate the potential use of medullary and metaplastic histology subtype and positive axillary lymph node metastasis as a potential biomarker in predicting relapse and survival of the TNBC patients. This warrants further studies on intensification of chemotherapy and also identification and development of targeted therapy to reduce relapses and improve survival of TNBC patients.
Fulltext Association of Arg72Pro of P53 polymorphism with colorectal cancer susceptibility risk in Malaysian population

Aizat AA, Shahpudin SN, Mustapha MA, Zakaria Z, Sidek AS, Abu Hassan MR, et al.

Asian Pac J Cancer Prev, 2011;12(11):2909-13.
PMID: 22393962

BACKGROUND: Colorectal cancer (CRC) results from the interaction between environmental exposures and genetic predisposition factors.

AIMS: A case control study was designed and to investigate the genotype frequencies of P53Arg72Pro polymorphism in Malaysian CRC patients and healthy controls and to determine the associated risk of this polymorphism with CRC predisposition.

METHODS: In this case-control study, peripheral blood samples of 202 sporadic CRC patients and 201 normal controls were collected, DNA extracted and genotyped using the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) technique.

RESULTS: Genotype analysis showed the frequency of homozygous variant (Pro/Pro) genotype (21%) to be significantly higher in cases compared to controls (13%), (p=0.013). On examining the association between variant genotypes and CRC risk, the Pro/Pro homozygous variant genotype showed significantly higher risk association with CRC susceptibility (OR: 2.047, CI: 1.063-4.044, p=0.033). When stratified according to age, we observed that, individuals aged above 50 years and carriers of pro/pro genotype had significantly higher risk with OR: 3.642, CI: 1.166-11.378, p=0.026.

CONCLUSIONS: Our results suggest that the codon 72 SNP which results in amino acid substitution of Arginine to Proline in cell cycle regulatory gene P53, is associated with sporadic CRC risk and carriers of Pro/Pro genotype and more than 50 years old may have high susceptibility.
Gender-specific association of NFKBIA promoter polymorphisms with the risk of sporadic colorectal cancer

Tan SC, Suzairi MS, Aizat AA, Aminudin MM, Nurfatimah MS, Bhavaraju VM, et al.

Med Oncol, 2013 Dec;30(4):693.
PMID: 23996241 DOI: 10.1007/s12032-013-0693-6

The inhibitory protein IκBα, encoded by the NFKBIA gene, plays an important role in regulating the activity of nuclear factor-kappa B, a transcription factor which has been implicated in the initiation and progression of cancers. This study aimed to evaluate the association of NFKBIA -826C>T (rs2233406) and -881A>G (rs3138053) polymorphisms with the risk of sporadic colorectal cancer (CRC) in Malaysian population. A case-control study comprising 474 subjects (237 CRC patients and 237 cancer-free controls) was carried out. The polymorphisms were genotyped from the genomic DNA of the study subjects employing PCR-RFLP, followed by DNA sequencing. The association between the polymorphic genotypes and CRC risk was evaluated by deriving odds ratios (ORs) and 95 % confidence intervals (CIs) using unconditional logistic regression analysis. The two polymorphisms were in complete and perfect linkage disequilibrium (D' = 1.0, r (2) = 1.0). Overall, no statistically significant CRC risk association was found for the polymorphisms (P > 0.05). A similar lack of association was observed when the data were stratified according to ethnicity (P > 0.05). However, stratification by gender revealed a significant inverse association between the heterozygous genotype of the polymorphisms and the risk of CRC among females (OR 0.53, 95 % CI 0.29-0.97, P = 0.04), but not among males (P > 0.05). In conclusion, the heterozygous genotype of the polymorphisms could contribute to a significantly decreased CRC risk among females, but not males, in the Malaysian population.
Fulltext Genetic Association of CYP1B1 4326 C>G Polymorphism with Disease-Free Survival in TNBC Patients Undergoing TAC Chemotherapy Regimen

Abdul Aziz AA, Md Salleh MS, Yahya MM, Zakaria AD, Ankathil R

Asian Pac J Cancer Prev, 2021 Apr 01;22(4):1319-1324.
PMID: 33906328 DOI: 10.31557/APJCP.2021.22.4.1319

BACKGROUND: Triple negative breast cancer (TNBC) which is treated with taxane, adriamycin and cyclophosphamide (TAC) chemotherapy regimen show variation in treatment response. CYP1B1 4326 C>G polymorphism has been implicated in contributing to the differences in treatment response in various types of cancers.
AIM: The objective of the present study was to investigate whether this polymorphism modulate the risk of disease recurrence in TNBC patients undergoing TAC chemotherapy regimen.
METHODS: Blood samples of 76 immunohistochemistry confirmed TNBC patients were recruited. The genotyping of CYP1B1 4326 C>G polymorphism was carried out using PCR-RFLP technique. The genotype patterns were categorized into homozygous wildtype, heterozygous and homozygous variant. Kaplan-Meier analysis followed by Cox proportional hazard regression model were performed to evaluate the TNBC patients' recurrence risk.
RESULTS: Out of 76 TNBC patients, 25 (33.0%) showed disease recurrence after one-year evaluation. Kaplan Meier analysis showed that TNBC patients who are carriers of CYP1B1 4326 GG variant genotypes (37.0%) had a significantly lower probability of disease-free rates as compared to TNBC patients who are carriers of CYP1B1 4326 CC/CG genotypes (71.0%). Univariate and multivariate Cox analysis demonstrated that TNBC patients who carried CYP1B1 4326 GG variant genotype had a significantly higher risk of recurrence with HR: 2.50 and HR: 4.18 respectively, even after adjustment as compared to TNBC patients who were carriers of CYP1B1 4326 CC and CG genotypes.
CONCLUSION: Our results demonstrate the potential use of CYP1B1 4325 GG variant genotype as a candidate biomarker in predicting risk of recurrence in TNBC patients undergoing TAC chemotherapy regimen.
Fulltext KRAS Mutational Profiles among Colorectal Cancer Patients in the East Coast of Peninsular Malaysia

Hasbullah HH, Sulong S, Che Jalil NA, Abdul Aziz AA, Musa N, Musa M

Diagnostics (Basel), 2023 Feb 21;13(5).
PMID: 36899966 DOI: 10.3390/diagnostics13050822

BACKGROUND: KRAS is a key driver gene in colorectal carcinogenesis. Despite this, there are still limited data on the mutational status of KRAS amongst colorectal cancer (CRC) patients in Malaysia. In the present study, we aimed to analyze the KRAS mutational profiles on codons 12 and 13 amongst CRC patients in Hospital Universiti Sains Malaysia, Kelantan, located on the East Coast of Peninsular Malaysia.
METHODS: DNA were extracted from formalin-fixed, paraffin-embedded tissues obtained from 33 CRC patients diagnosed between 2018 and 2019. Amplifications of codons 12 and 13 of KRAS were conducted using conventional polymerase chain reaction (PCR) followed by Sanger sequencing.
RESULTS: Mutations were identified in 36.4% (12/33) of patients, with G12D (50%) being the most frequent single-point mutation observed, followed by G12V (25%), G13D (16.7%), and G12S (8.3%). No correlation was found between mutant KRAS and location of the tumor, staging, and initial carcinoembryonic antigen (CEA) level.
CONCLUSION: Current analyses revealed that a significant proportion of CRC patients in the East Coast of Peninsular Malaysia have KRAS mutations, where this frequency is higher compared to those in the West Coast. The findings of this study would serve as a precursor for further research that explores KRAS mutational status and the profiling of other candidate genes among Malaysian CRC patients.
Fulltext Perspectives on the Application of Cytogenomic Approaches in Chronic Lymphocytic Leukaemia

Wan Mohamad Zamri WN, Mohd Yunus N, Abdul Aziz AA, Zulkipli NN, Sulong S

Diagnostics (Basel), 2023 Mar 03;13(5).
PMID: 36900108 DOI: 10.3390/diagnostics13050964

Chronic lymphocytic leukaemia (CLL) is a haematological malignancy characterised by the accumulation of monoclonal mature B lymphocytes (positive for CD5+ and CD23+) in peripheral blood, bone marrow, and lymph nodes. Although CLL is reported to be rare in Asian countries compared to Western countries, the disease course is more aggressive in Asian countries than in their Western counterparts. It has been postulated that this is due to genetic variants between populations. Various cytogenomic methods, either of the traditional type (conventional cytogenetics or fluorescence in situ hybridisation (FISH)) or using more advanced technology such as DNA microarrays, next generation sequencing (NGS), or genome wide association studies (GWAS), were used to detect chromosomal aberrations in CLL. Up until now, conventional cytogenetic analysis remained the gold standard in diagnosing chromosomal abnormality in haematological malignancy including CLL, even though it is tedious and time-consuming. In concordance with technological advancement, DNA microarrays are gaining popularity among clinicians as they are faster and better able to accurately diagnose the presence of chromosomal abnormalities. However, every technology has challenges to overcome. In this review, CLL and its genetic abnormalities will be discussed, as well as the application of microarray technology as a diagnostic platform.
Fulltext Association of ABCG2 Polymorphisms on Triple Negative Breast Cancer (TNBC) Susceptibility Risk

Hao Ing Y, Md Salleh MS, Yahya MM, Ankathil R, Abdul Aziz AA

Asian Pac J Cancer Prev, 2023 Nov 01;24(11):3891-3897.
PMID: 38019248 DOI: 10.31557/APJCP.2023.24.11.3891

OBJECTIVE: The aim of this study was to elucidate the association of ATP-binding cassette super-family G member 2 (ABCG2) gene polymorphisms with individual susceptibility to Triple Negative Breast Cancer (TNBC) as well as clinicopathological variables in TNBC patients. Two common polymorphisms in Asian population, ABCG2 34 G>A and 421 C>A was selected in this study.
METHODS: Blood samples were collected from 75 TNBC patients and 83 controls. Genomic DNA was extracted from blood samples and the SNP genotyping was performed by using PCR-RFLP technique. The genotypes were characterized and grouped into homozygous wildtype, heterozygote and homozygous variant based on the band size. The result was subjected to statistical analysis.
RESULTS: The A allele and AA genotype of ABCG2 421 C>A had OR of 3.011 (p=0.003, 95% CI: 1.417-6.398) and 9.042 (p=0.011, 95% CI: 1.640-49.837), to develop advanced staging carcinoma respectively. The AA genotype of ABCG2 421 C>A polymorphism was also associated with metaplastic and medullary carcinoma with an OR of 6.429 (p=0.018, 95% CI: 1.373-30.109). A significant association was also found in haplotype 34G/421A of ABCG2 with advanced cancer staging as well as metaplastic and medullary carcinoma with OR of 2.347 (p=0.032, 95% CI: 1.010-5.560) and 2.546 (p=0.008, 95% CI: 1.005-6.447), respectively. Conclusion: The present study suggests that ABCG2 421 C>A polymorphism was associated with metaplastic and medullary histology and advanced cancer staging in TNBC patients.
Enantioselective dihydroxylation of xanthorrhizol from Curcuma xanthorrhiza via biotransformation using Aspergillus Niger

Aminudin NI, Abdul Aziz AA, Zainal Abidin ZA, Susanti D, Taher M

Nat Prod Res, 2024 May;38(9):1583-1590.
PMID: 36577029 DOI: 10.1080/14786419.2022.2161543

Biotransformation is acknowledged as one of the green chemistry methods to synthesis various analogues for further valorization of natural product compounds chemistry and bioactivities. It has huge advantage over chemical synthesis due to its cost-efficiency and higher selectivity. In this work, a xanthorrhizol derivatives, namely (7 R,10S)-10,11-dihydro-10,11-dihydroxyxanthorrhizol was produced in 60% yield from the biotransformation process utilizing A. niger. The structure of the compound was established by extensive spectroscopic methods and comparison with literature data. This biotransformation successfully afforded enantioselective dihydroxylation reaction via green chemistry route. This is the first report on both biotransformation of xanthorrhizol and utilization of A. niger as its biocatalyst.
Fulltext Anxiety, depression, coronary artery disease and diabetes mellitus; an association study in ghaem hospital, iran

Tajfard M, Ghayour Mobarhan M, Rahimi HR, Mouhebati M, Esmaeily H, Ferns GA, et al.

Iran Red Crescent Med J, 2014 Sep;16(9):e14589.
PMID: 25593715 DOI: 10.5812/ircmj.14589

There is an increasing trend in the prevalence of coronary artery disease (CAD) in Iran.
Contribution of the MLH1 -93G>a promoter polymorphism in modulating susceptibility risk in Malaysian colorectal cancer patients

Nizam ZM, Abdul Aziz AA, Kaur G, Abu Hassan MR, Mohd Sidek AS, Yeh LY, et al.

Asian Pac J Cancer Prev, 2013;14(2):619-24.
PMID: 23621208

BACKGROUND: Colorectal cancer (CRC) exists in a more common sporadic form and less common hereditary forms, associated with the Lynch syndrome, familial adenomatous polyposis (FAP) and other rare syndromes. Sporadic CRC is believed to arise as a result of close interaction between environmental factors, including dietary and lifestyle habits, and genetic predisposition factors. In contrast, hereditary forms such as those related to the Lynch syndrome result from inheritance of germline mutations of mismatch repair (MMR) genes. However, in certain cases, the influence of low penetrance alleles in familial colorectal cancer susceptibility is also undeniable.
AIM: To investigate the genotype frequencies of MLH1 promoter polymorphism -93G>A and to determine whether it could play any role in modulating familial and sporadic CRC susceptibility risk.
METHODS: A case-control study comprising of 104 histopathologically confirmed CRC patients as cases (52 sporadic CRC and 52 Lynch syndrome patients) and 104 normal healthy individuals as controls was undertaken. DNA was extracted from peripheral blood and the polymorphism was genotyped employing PCR-RFLP methods. The genotypes were categorized into homozygous wild type, heterozygous and homozygous variants. The risk association between these polymorphisms and CRC susceptibility risk was calculated using binary logistic regression analysis and deriving odds ratios (ORs).
RESULTS: When risk association was investigated for all CRC patients as a single group, the heterozygous (G/A) genotype showed a significantly higher risk for CRC susceptibility with an OR of 2.273, (95%CI: 1.133-4.558 and p-value=0.021). When analyzed specifically for the 2 types of CRC, the heterozygous (G/A) genotype showed significantly higher risk for sporadic CRC susceptibility with and OR of 3.714, (95%CI: 1.416-9.740 and p-value=0.008). Despite high OR value was observed for Lynch syndrome (OR: 1.600, 95%CI: 0.715-3.581), the risk was not statistically significant (P=0.253).
CONCLUSION: Our results suggest an influence of MLH1 promoter polymorphism -93G>A in modulating susceptibility risk in Malaysian CRC patients, especially those with sporadic disease.
Single-nucleotide polymorphisms and mRNA expression of CYP1B1 influence treatment response in triple negative breast cancer patients undergoing chemotherapy

Abdul Aziz AA, Md Salleh MS, Mohamad I, Krishna Bhavaraju VM, Mazuwin Yahya M, Zakaria AD, et al.

J Genet, 2018 Dec;97(5):1185-1194.
PMID: 30555068

Triple negative breast cancer (TNBC) is typically associated with poor and interindividual variability in treatment response. Cytochrome P450 family 1 subfamily B1 (CYP1B1) is a metabolizing enzyme, involved in the biotransformation of xenobiotics and anticancer drugs. We hypothesized that, single-nucleotide polymorphisms (SNPs), CYP1B1 142 C>G, 4326 C>G and 4360 A>G, and CYP1B1 mRNA expression might be potential biomarkers for prediction of treatment response in TNBC patients. CYP1B1 SNPs genotyping (76 TNBC patients) was performed using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods and mRNA expression of CYP1B1 (41 formalin-fixed paraffin embeddedblocks) was quantified using quantitative reverse transcription PCR. Homozygous variant genotype (GG) and variant allele (G) of CYP1B1 4326C>G polymorphism showed significantly higher risk for development of resistance to chemotherapy with adjusted odds ratio (OR): 6.802 and 3.010, respectively. Whereas, CYP1B1 142 CG heterozygous genotype showed significant association with goodtreatment response with adjusted OR: 0.199. CYP1B1 142C-4326G haplotype was associated with higher risk for chemoresistance with OR: 2.579. Expression analysis revealed that the relative expression of CYP1B1 was downregulated (0.592) in cancerous tissue compared with normal adjacent tissues. When analysed for association with chemotherapy response, CYP1B1 expression was found to be significantly upregulated (3.256) in cancerous tissues of patients who did not respond as opposed to those of patients who showed response to chemotherapy. Our findings suggest that SNPs together with mRNA expression of CYP1B1 may be useful biomarkers to predict chemotherapy response in TNBC patients.
Giant Intradiverticular Bladder Tumor

Md Noh MS, Abdul Aziz AF, Mohd Ghani KA, Lee Kheng Siang C, Yunus R, Mohd Yusof M

Am J Case Rep, 2017 Mar 01;18:212-216.
PMID: 28246375

BACKGROUND Intradiverticular bladder tumors are rare. This renders diagnosis of an intradiverticular bladder tumor difficult. Imaging plays a vital role in achieving the diagnosis, and subsequently staging of the disease. CASE REPORT A 74-year-old male presented to our center with a few months history of constitutional symptoms. Upon further history, he reported hematuria two months prior to presentation, which stopped temporarily, only to recur a few days prior to coming to the hospital. The patient admitted to having lower urinary tract symptoms. However, there was no dysuria, no sandy urine, and no fever. Palpation of his abdomen revealed a vague mass at the suprapubic region, which was non tender. In view of his history and the clinical examination findings, an ultrasound of the abdomen and computed tomography (CT) was arranged. These investigations revealed a giant tumor that seemed to be arising from a bladder diverticulum, with a mass effect and hydronephrosis. He later underwent operative intervention. CONCLUSIONS Intradiverticular bladder tumors may present a challenge to the treating physician in an atypical presentation; thus requiring a high index of suspicion and knowledge of tumor pathophysiology. As illustrated in our case, CT with its wide availability and multiplanar imaging capabilities offers a useful means for diagnosis, disease staging, operative planning, and follow-up.
Fulltext Contribution of Genetic Polymorphisms of Inflammation Response Genes on Sporadic Colorectal Cancer Predisposition Risk in Malaysian Patients - A Case Control Study

Ankathil R, Mustapha MA, Abdul Aziz AA, Mohd Shahpudin SN, Zakaria AD, Abu Hassan MR, et al.

Asian Pac J Cancer Prev, 2019 06 01;20(6):1621-1632.
PMID: 31244280 DOI: 10.31557/APJCP.2019.20.6.1621

AIM: To investigate the frequencies and association of polymorphic genotypes of IL-8 -251 T>A, TNF-α -308
G>A, ICAM-1 K469E, ICAM-1 R241G, IL-6 -174 G>C, and PPAR-γ 34 C>G in modulating susceptibility risk in
Malaysian colorectal cancer (CRC) patients. Methods: In this case-control study, peripheral blood samples of 560
study subjects (280 CRC patients and 280 controls) were collected, DNA extracted and genotyped using PCR-RFLP
and Allele Specific PCR. The association between polymorphic genotype and CRC susceptibility risk was determined
using Logistic Regression analysis deriving Odds ratio (OR) and 95% CI. Results: On comparing the frequencies of
genotypes of all single nucleotide polymorphisms ( SNPs ) in patients and controls, the homozygous variant genotypes
IL-8 -251 AA and TNF-α -308 AA and variant A alleles were significantly higher in CRC patients. Investigation on
the association of the variant alleles and genotypes singly, with susceptibility risk showed the homozygous variant A
alleles and genotypes IL-8 -251 AA and TNF-α -308 AA to be at higher risk for CRC predisposition. Analysis based
on age, gender and smoking habits showed that the polymorphisms IL8 -251 T>A and TNF – α 308 G>A contribute
to a significantly higher risk among male and female who are more than 50 years and for smokers in this population.
Conclusion: We observed an association between variant allele and genotypes of IL-8-251 T>A and TNF-α-308
G>A polymorphisms and CRC susceptibility risk in Malaysian patients. These two SNPs in inflammatory response
genes which undoubtedly contribute to individual risks to CRC susceptibility may be considered as potential genetic
predisposition factors for CRC in Malaysian population.
Fulltext Impact of Fas/Fasl Gene Polymorphisms on Susceptibility Risk and Imatinib Mesylate Treatment Response in Chronic Myeloid Leukaemia Patients

Annuar AA, Ankathil R, Mohd Yunus N, Husin A, Ab Rajab NS, Abdul Aziz AA, et al.

Asian Pac J Cancer Prev, 2021 Feb 01;22(2):565-571.
PMID: 33639675 DOI: 10.31557/APJCP.2021.22.2.565

BACKGROUND: The FAS mediated apoptosis pathway involving the FAS and FASL genes plays a crucial role in the regulation of apoptotic cell death and imatinib mesylate (IM) mechanism of action. Promoter polymorphisms FAS-670 A>G and FAS-844 T>C which alter the transcriptional activity of these genes may grant a risk to develop cancer and revamp the drug activities towards the cancer cell. We investigated the association of these two polymorphisms with the susceptibility risk and IM treatment response in Malaysian chronic myeloid leukaemia (CML) patients.
METHODS: This is a retrospective study, which included 93 CML patients and 98 controls. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method was used to genotype the FAS and FASL polymorphisms. Data nanlysis was done using SPSS Version 22. The associations of the genotypes with susceptibility risk and IM response in CML patients were assessed by means of logistic regression analysis and deriving odds ratio with 95% CI.
RESULTS: We observed a significant association between FASL-844T>C polymorphism and CML susceptibility risk and IM response. Variant C allele and FASL-844 CC variant genotype carriers had significantly higher risk for CML susceptibility (OR 1.756, CI 1.163-2.652, p=0.007 and OR 2.261, CI 1.013-5.047, p=0.047 respectively). Conversely, the heterozygous genotype FASL-844 TC conferred lower risk for CML susceptibility (OR 0.379, CI 0.176-0.816, p=0.013). The heterozygous and homozygous variant genotypes and variant C alleles were found to confer a lower risk for the development of IM resistance with OR 0.129 (95% CI: 0.034-0.489 p=0.003), OR 0.257 (95% CI: 0.081-0.818, p=0.021), and OR 0.486 (95% CI: 0.262-0.899, p=0.021) respectively. We also found that FAS-670 A>G polymorphism was not associated with CML susceptibility risk or IM response.
CONCLUSION: The genetic polymorphism FASL-844 T>C may contribute to the CML susceptibility risk and also IM treatment response in CML patients. Accodringly, it may be useful as a biomarker for predicting CML susceptibility risk and IM resistance.
Fulltext A GNAS Gene Mutation's Independent Expression in the Growth of Colorectal Cancer: A Systematic Review and Meta-Analysis

Afolabi HA, Salleh SM, Zakaria Z, Ch'ng ES, Mohd Nafi SN, Abdul Aziz AAB, et al.

Cancers (Basel), 2022 Nov 08;14(22).
PMID: 36428574 DOI: 10.3390/cancers14225480

Globally, colorectal carcinoma CRC is the third most common cancer and the third most common reason for cancer-associated mortality in both genders. The GNAS mutations are significantly linked with poor prognosis and failed treatment outcomes in CRC. A systematic review and meta-analysis of multiple studies executed following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) criteria and registered with PROSPERO (registration number: CRD42021256452). The initial search includes a total of 271 publications; however, only 30 studies that merit the eligibility criteria were eventually chosen. Data analysis via OpenMeta Analyst and comprehensive meta-analysis 3.0 (CMA 3.0) software were used to investigate the prevalence of GNAS gene mutation among CRC patients. The meta-analysis consisted of 10,689 participants with most being males 6068/10,689 (56.8%). Overall, prevalence of GNAS mutations was 4.8% (95% CI: 3.1−7.3) with I2 = 94.39% and (p < 0.001). In 11/30 studies, the frequency of GNAS gene mutations was majorly in codons R201C [40.7% (95% CI: 29.2−53.2%)] and in codon R201H [39.7% (95% CI = 27.1−53.8)]. Overall prevalence of GNAS mutations was highest among the male gender: 53.9% (95% CI: 48.2−59.5%: I2 = 94.00%, (p < 0.001), tumour location (colon): 50.5% (95% CI: 33.2−67.6%: I2 = 97.93%, (p < 0.001), tumour grade (Well): 57.5% (95% CI: 32.4−79.2%: I2 = 98.10%, (p < 0.001) and tumour late stage: 67.9% (95% CI: 49.7−84.3%: I2 = 98.%, (p < 0.001). When stratified according to study location, a higher prevalence was observed in Japan (26.8%) while Italy has the lowest (0.4%). Overall prevalence of GNAS gene mutations was 4.8% with codons R201C and R201H being the most mutated, and the results conformed with numerous published studies on GNAS mutation.
Fulltext The Prediction of Survival Outcome and Prognosis Factor in Association with Comorbidity Status in Patients with Colorectal Cancer: A Research-Based Study

Afolabi H, Salleh SM, Zakaria Z, Ch'ng ES, Mohd Nafi SN, Abdul Aziz AAB, et al.

Healthcare (Basel), 2022 Sep 05;10(9).
PMID: 36141305 DOI: 10.3390/healthcare10091693

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.
Fulltext Valorization of Peanut Skin as Agricultural Waste Using Various Extraction Methods: A Review

Putra NR, Rizkiyah DN, Che Yunus MA, Abdul Aziz AH, Md Yasir ASH, Irianto I, et al.

Molecules, 2023 May 25;28(11).
PMID: 37298801 DOI: 10.3390/molecules28114325

Peanuts (Arachis hypogea) can be made into various products, from oil to butter to roasted snack peanuts and candies, all from the kernels. However, the skin is usually thrown away, used as cheap animal feed, or as one of the ingredients in plant fertilizer due to its little value on the market. For the past ten years, studies have been conducted to determine the full extent of the skin's bioactive substance repertoire and its powerful antioxidant potential. Alternatively, researchers reported that peanut skin could be used and be profitable in a less-intensive extraction technique. Therefore, this review explores the conventional and green extraction of peanut oil, peanut production, peanut physicochemical characteristics, antioxidant activity, and the prospects of valorization of peanut skin. The significance of the valorization of peanut skin is that it contains high antioxidant capacity, catechin, epicatechin resveratrol, and procyanidins, which are also advantageous. It could be exploited in sustainable extraction, notably in the pharmaceutical industries.

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