Displaying publications 1 - 20 of 35 in total

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  1. Che Alhadi S, Wan Zain WZ, Zahari Z, Md Hashim MN, Syed Abd Aziz SH, Zakaria Z, et al.
    Ann Coloproctol, 2020 Dec;36(6):409-414.
    PMID: 32972105 DOI: 10.3393/ac.2020.08.27
    PURPOSE: Guaiac fecal occult blood test (gFOBT) has been the standard for colorectal screening but it has low sensitivity and specificity. This study evaluated the use of fecal tumor M2-pyruvate kinase (M2-PK) for detection of colorectal cancer and to compare with the current surveillance tool; gFOBT in symptomatic adult subjects underwent colonoscopy.

    METHODS: Stool samples were collected prospectively from symptomatic adults who had elective colonoscopy from September 2014 to January 2016 and were analyzed with the ScheBo M2-PK Quick test and laboratory detection of fecal hemoglobin.

    RESULTS: The results were correlated to the colonoscopy findings and/or histopathology report. Eighty-five subjects (age of 56.8 ± 15.3 years [mean ± standard deviation]) were recruited with a total of 17 colorectal cancer (20.0%) and 10 colorectal adenoma patients (11.8%). The sensitivity of M2-PK test in colorectal cancer detection was higher than gFOBT (100% vs. 64.7%). M2-PK test had a lower specificity when compared to gFOBT (72.5% vs. 88.2%) in colorectal cancer detection. The positive and negative predictive values were 47.2% and 100% for M2-PK test and 57.9% and 90.9% for gFOBT.

    CONCLUSION: Fecal M2-PK Quick test has a high sensitivity for detection of colorectal cancer when compared to gFOBT, making it the potential choice for colorectal tumor screening biomarker in the future.

  2. Pushpanathan NR, Hashim MNM, Zahari Z, Aziz SHSA, Zain WZW, Ramely R, et al.
    Ann Coloproctol, 2022 Dec;38(6):409-414.
    PMID: 34407370 DOI: 10.3393/ac.2020.00437.0062
    PURPOSE: Laparoscopic appendicectomy (LA) has several advantages over conventional open appendicectomy (OA). However, about 5% to 10% of LA patients still need to be converted to open surgery. Identifying risk factors that contribute to conversion to OA allows for early identification of patients who may benefit from primary OA. This study aimed to determine the conversion rate of LA to OA and to identify its associated risk factors among patients with acute or perforated appendicitis.

    METHODS: A retrospective review of medical records was performed among patients with acute or perforated appendicitis who underwent LA between December 2015 and January 2017. With the use of multivariable logistic regression analyses, the predictors of conversion from laparoscopic to OA were investigated.

    RESULTS: Out of 120 patients, 33 cases were converted to OA which gives a conversion rate of 27.5%. Among 33 patients who were converted to OA, 27 patients (81.8%) had perforated appendix, while in the LA group, perforated appendix cases consisted of 34.5% (P<0.001). Histopathology of the appendix was the predictor of conversion from LA to OA (adjusted odds ratio, 8.82; 95% confidence interval, 3.13-24.91; P<0.001).

    CONCLUSION: The result from our study shows that the overall conversion rate for the study period was high. Patients with perforated appendicitis had a higher risk of conversion to OA. Therefore, preoperative diagnosis of perforated appendicitis may be paramount in predicting conversion to OA.

  3. Lim SL, Wan Zain WZ, Zahari Z, Zakaria AD, Hashim MNM, Wong MP, et al.
    Ann Coloproctol, 2023 Oct;39(5):427-434.
    PMID: 35655395 DOI: 10.3393/ac.2022.00227.0032
    PURPOSE: Oncological outcomes following rectal cancer surgery have improved significantly over recent decades with lower recurrences and longer overall survival. However, many of the patients experienced low anterior resection syndrome (LARS). This study identified the prevalence and risk factors associated with the development of LARS.

    METHODS: This cross-sectional study involved patients who were diagnosed with rectal cancer and had undergone sphincter-preserving low anterior resection from January 2011 to December 2020. Upon clinic follow-up, patients were asked to complete an interviewed based questionnaire (LARS score) designed to assess bowel dysfunction after rectal cancer surgery.

    RESULTS: Out of 76 patients, 25 patients (32.9%) had major LARS, 10 patients (13.2%) had minor LARS, and 41 patients (53.9%) had no LARS. The height of tumor from anal verge showed an association with the development of major LARS (P=0.039). Those patients with less than 8 cm tumor from anal verge had an increased risk of LARS by 3 times compared to those with 8 cm and above (adjusted odds ratio, 3.11; 95% confidence interval, 1.06-9.13).

    CONCLUSION: Results from our study show that low tumor height was a significant risk factor that has a negative impact on bowel function after surgery. The high prevalence of LARS emphasizes the need for study regarding risk factors and the importance of understanding the pathophysiology of LARS, in order for us to improve patient bowel function and quality of life after rectal cancer surgery.

  4. Teoh ZH, Soh JY, Mohamad N, Zawawi N, Zakaria AD, Zakaria Z, et al.
    Ann Coloproctol, 2022 Nov 25.
    PMID: 36424815 DOI: 10.3393/ac.2022.00549.0078
    Juvenile polyps (JPs) are the most common polyps in pediatric patients. We present the case of an 18-year-old male patient with a giant solitary JP resembling solitary rectal ulcer syndrome (SRUS). The presenting history was rectal bleeding and symptoms of obstructed defecation syndrome. Colonoscopy revealed a polypoidal mass at the anorectal junction, with biopsy-confirmed SRUS. The symptoms worsened, and a protruding mass from the anus caused fecal incontinence. Pelvic magnetic resonance imaging showed a huge pedunculated mass occupying the low rectum with local compression of the urinary bladder. Transanal excision of the anal tumor was performed due to bleeding. A histopathological examination showed a JP with high-grade dysplasia. A histological examination to differentiate JPs and SRUS could be challenging based on a superficial forceps biopsy. Therefore, an excision biopsy is usually warranted with the understanding that adenomatous or malignant transformation is found in 5.6% to 12% of all JPs.
  5. Tan PG, Ab Hadi IS, Zahari Z, Yahya MM, Wan Zain WZ, Wong MP, et al.
    Ann Surg Treat Res, 2020 Jan;98(1):1-6.
    PMID: 31909044 DOI: 10.4174/astr.2020.98.1.1
    Purpose: Patients with secondary hyperparathyroidism are at high risk for developing postoperative hypocalcemia. However, there are limited data regarding predictors of postoperative hypocalcemia in renal failure patient with secondary hyperparathyroidism. This study aimed to determine the clinical presentations of renal hyperparathyroidism and the predictors of early postoperative hypocalcemia after total parathyroidectomy.

    Methods: Data of patients with renal hyperparathyroidism who underwent total parathyroidectomy between January 2007 to December 2014 were reviewed retrospectively. Patients were divided into 2 cohort groups according to their serum calcium levels within 24 hours of parathyroidectomy: the hypocalcemia group (calcium levels of 2 mmol/L or less), and the normocalcemia group (calcium levels more than 2 mmol/L). With the use of multivariable logistic regression analyses, the predictors of early postoperative hypocalcemia after total parathyroidectomy in patients with renal hyperparathyroidism were investigated.

    Results: Among 68 patients, 56 patients (82.4%) were symptomatic preoperatively. Fifty patients (73.5%) presented with bone pain and 14 patients (20.6%) had muscle weakness. Early postoperative hypocalcemia occurred in 25 patients (36.8%). Preoperative alkaline phosphatase level was the predictor of early postoperative hypocalcemia (adjusted odds ratio, 1.004; 95% confidence interval, 1.001-1.006; P = 0.002).

    Conclusion: Results from our study show that most of the patients with renal hyperparathyroidism were symptomatic preoperatively and the most common clinical presentations were bone pain and muscle weakness. The significant predictor of early postoperative hypocalcemia after total parathyroidectomy was the preoperative alkaline phosphatase levels.

  6. Wan Juhari WK, Wan Abdul Rahman WF, Mohd Sidek AS, Abu Hassan MR, Ahmad Amin Noordin KB, Zakaria AD, et al.
    Asian Pac J Cancer Prev, 2015;16(9):3767-71.
    PMID: 25987035
    BACKGROUND: Lynch syndrome (LS) is an inherited predisposition to colorectal, endometrial (uterine) and other cancers. Although most cancers are not inherited, about 5 percent (%) of people who have colorectal or endometrial cancer have the Lynch syndrome. It involves the alteration of mismatch repair (MMR) genes; MLH1, MSH2, MSH6 or PMS2. In this study, we analyzed the expression of MMR proteins in colorectal cancer in a Malay cohort by immunohistochemistry.

    MATERIALS AND METHODS: A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2.

    RESULTS: Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression of MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expression in two tumour tissues respectively.

    CONCLUSIONS: Revised Bethesda criteria and immunohistochemical analysis constituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malay cohorts.

  7. Hayati F, Mohd Azman ZA, Nasuruddin DN, Mazlan L, Zakaria AD, Sagap I
    Asian Pac J Cancer Prev, 2017 07 27;18(7):1821-1825.
    PMID: 28749112
    Background: Anastomotic leaks in colorectal surgery results in a high morbidity and mortality rate. Serum procalcitonin levels is known as a sensitive and specific marker of sepsis and could be use as a marker for early detection of a leak allowing early intervention. It may help a clinician decide to perform a CT scan even earlier especially when the diagnosis of a leak is uncertain. The aim of this study is to determine whether serum procalcitonin is a good predictor of anastomotic leak in colorectal surgery. Methodology: Between July 2014 until October 2015, 70 patients undergoing colorectal surgery were prospectively analyzed in a single-center tertiary teaching hospital. Demographic and surgical data were obtained. Serum procalcitonin was taken before surgery and at day 3 (72 hours) postoperatively. During the postoperative period, the patients were observed in the ward for features of anastomotic leak and if present, it was managed accordingly. The primary outcome was to prospectively determine an association between serum procalcitonin levels and an anastomotic leak in patients who underwent colorectal surgery with a primary anastomosis. Result: The rate of anastomotic leak was 4.5% (3 patients) with a mortality rate of 4.3% (3 patients). A rise in serum procalcitonin was statistically significant among patients with anastomotic leak. The optimal procalcitonin cut-off level at postoperative day 3 was 5.27 ng/mL, resulting in 100% sensitivity, 85% specificity, 23% positive predictive value and 100% negative predictive value. Nevertheless, none of the variables showed statistical significance with an anastomotic leak. Conclusion: Procalcitonin is a reliable biochemical marker to help diagnose anastomotic leak in colorectal surgery. Our study has shown that a level of 5 times beyond normal is statistically significant and a value of more than 5.27 ng/mL is confirmatory of a leak.
  8. 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.
  9. 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.

  10. Ahmad Zawawi SS, Mohd Azram NAS, Sulong S, Zakaria AD, Lee YY, Che Jalil NA, et al.
    Asian Pac J Cancer Prev, 2023 Sep 01;24(9):3099-3107.
    PMID: 37774061 DOI: 10.31557/APJCP.2023.24.9.3099
    BACKGROUND: Accumulation of cancer-associated fibroblasts (CAFs) in the tumor stroma is linked to poor prognosis in colorectal cancer (CRC). CAF-cancer cell interplay, facilitated by secretomes including transforming growth factor-beta 1 (TGF-β1), supports fibroblast activation, drives colorectal carcinogenesis, and contributes to CRC aggressive phenotypes. Although widely used, traditional CAF biomarkers are found to have heterogeneous and non-specific expression. Amine oxidase copper containing 3 (AOC3) and leucine-rich repeat-containing 17 (LRRC17) have been reported to be emerging markers of myofibroblasts.

    AIM: Our objective was to investigate the potential of AOC3 and LRRC17 as biomarkers for fibroblast activation thus predicting their roles in CRC progression.

    METHODS: Immunofluorescence (IF) staining of AOC3 and LRRC17 was performed on myofibroblast line (CCD-112CoN), primary fibroblasts from colorectal tumor (CAFs), and adjacent normal tissue (normal fibroblasts-NFs). SW620 (epithelial CRC cell line) was used as a control.  Conventional CAF biomarker (alpha-smooth muscle actin - α-SMA) was included in the IF analysis. Fluorescence intensity was compared between groups using ImageJ software. Proliferation and contractility of treated cells were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and collagen gel contraction assays, respectively. Fibroblast contraction under TGF-β1 treatment was compared to those treated with complete medium (addition of 10% serum) and serum free (SF) medium.

    RESULTS: Positive AOC3, LRRC17, and α-SMA expression were observed in colonic fibroblasts, more prominent in CAFs, whereas negative staining was found in SW620. Significant downregulation of AOC3, and upregulations in LRRC17 and α-SMA expression was found in TGF-β1-treated fibroblasts compared to SF medium treatment (p-value<0.05). All fibroblasts exhibited higher proliferation in complete medium and under treatment with conditioned medium from SW620 than SF medium. Significant contraction of NFs was recorded in complete medium and TGF-β1 (p-value<0.01).

    CONCLUSION: Our results demonstrate AOC3 and LRRC17 as the potential markers of CAF activation which promote CRC progression.

  11. Yaacob H, Ikhwan SM, Hashim MN, Syed Abd Aziz SH, Wan Zain WZ, Tuan Sharif SE, et al.
    Asian J Endosc Surg, 2018 Nov;11(4):318-324.
    PMID: 29424061 DOI: 10.1111/ases.12463
    INTRODUCTION: Colonoscopy is the gold standard to detect colorectal neoplasm. Narrow-band imaging (NBI) has a good diagnostic accuracy to differentiate between neoplastic and non-neoplastic colorectal lesions. This study explores the diagnostic validity of NBI colonoscopy as well as its associated factors related to neoplastic and non-neoplastic colorectal lesions.

    METHODS: This study enrolled 100 patients in a single-center tertiary teaching hospital. Patients presented for screening colonoscopy, and those with suspicious colorectal lesions were included in this study. During colonoscopy, the most suspicious lesion in each patient was analyzed using the NBI system based on Sano's classification. Each lesion was biopsied for histopathological analysis, the gold standard. Endoscopic images were captured electronically. The sensitivity, specificity, and diagnostic accuracy of NBI colonoscopy were assessed. Other associated factors related to neoplastic and non-neoplastic lesions were analyzed accordingly.

    RESULTS: The sensitivity and specificity of the NBI were 88.2% and 71.9%, respectively. The area under the receiver-operator curve was 0.801, indicating that NBI has a good ability to differentiate between disease and non-disease. There are significant associations between histopathological examination outcomes and both presenting symptoms, especially weight loss, and lesion site, even after other variables were controlled (P 

  12. Aznan MI, Khan OH, Unar AO, Tuan Sharif SE, Khan AH, Syed Abd Aziz SH, et al.
    BMC Complement Altern Med, 2016 Jan 23;16:28.
    PMID: 26803744 DOI: 10.1186/s12906-016-1003-6
    BACKGROUND: Honey has long been used for the treatment of number of ailments and diseases including surgical wounds. Current study evaluates the effectiveness of Tualang honey (TH) for large bowel anastomotic healing in Wistar rats.

    METHODS: Thirty male Wistar rats were given a 3 centimeter infra-umbilical laparotomy wound, in`flicted on their abdomen. The colonic transection was performed at 5 cm distal to caecum, with end to end anastomosis of colon segment. They were divided into two groups. Group I was fed with standard rat chow and water. Meanwhile, Group II apart from standard feed, was also given TH 1.0 g/kg every morning until day seven post operatively. Afterwards, anastomotic bursting pressures were measured and histopathological examination on the anastomosis line was performed with light microscopes. The data from two groups were analyzed by Independent paired t test for continuous variables.

    RESULTS: It was found that the tensile strength of colon anastomosis (95 % CI; p = <0.001) and the histopathological study including fibroblast count (p = <0.001) and inflammatory cells (p = 0.002) showed statistically significant difference in the favor of TH-treated group. Meanwhile, neovascularization formation was not statistically significant (p = 0.807); however, the overall count in the TH group was high.

    CONCLUSION: Oral treatment with TH enhances anastomotic wound healing by increasing the number of fibroblasts and by decreasing inflammatory cells leading towards increased wound strength.

  13. Jagwani AV, Fathi NQ, Jailani RF, Zakaria AD
    BMJ Case Rep, 2017 Jan 06;2017.
    PMID: 28062430 DOI: 10.1136/bcr-2016-217865
    Polyarteritis nodosa (PAN) is a systemic necrotising vasculitis preferentially targeting medium-sized arteries and not related with glomerulonephritis or small vessel involvement. Clinical manifestations of PAN are multisystem. The gastrointestinal, renal, cardiac, musculoskeletal, skin and central nervous systems may be involved. The aetiology remains unknown, and the ensuing vasculitis may lead to aneurysm formation and thrombosis in any organs of the body with resultant ischaemia. PAN of the intestines is a relatively common manifestation of this disease but rarely causes bowel ischaemia resulting in necrosis. Here we report a case of a young Chinese patient who presented with an acute abdomen requiring surgery and made good recovery post operatively. He remains free of symptoms while on steroid therapy.
  14. Ezrien DE, Hayati F, Nik Lah NAS, Zakaria AD
    BMJ Case Rep, 2019 Nov 24;12(11).
    PMID: 31767613 DOI: 10.1136/bcr-2019-232611
  15. Ilias AS, Yaacob H, Wan Zain WZ, Zakaria AD
    BMJ Case Rep, 2017 Sep 15;2017.
    PMID: 28918402 DOI: 10.1136/bcr-2017-219826
    We experienced a rare case of primary leiomyosarcoma of sigmoid mesentery. A 45-year-old woman was presented to us with left iliac fossa mass and discomfort for 4-month duration. CT scan of abdomen and pelvis revealed a huge mass 14 cm×14 cm×16 cm occupying left iliac fossa mimicked having a large left ovarian carcinoma. She was subsequently planned for elective total abdominal hysterectomy and bilateral salpingo-oophorectomy by gynaecology team. During laparotomy, a huge mass was revealed arising from sigmoid mesentery invaded to the left lower ureter. Curative resection was done and pathological findings show the tumour being leiomyosarcoma with immunohistochemistry tests on caldesmon, desmin, smooth muscle actin and CD34 reagent all positive. Clinicopathological and literature review of this rare primary leiomyosarcoma of mesocolon was discussed in our case presentation.
  16. Chong TH, Asyraf MZ, Hayati F, Azizan N, Sahid NA, Ting JRS, et al.
    Case Rep Surg, 2018;2018:4606259.
    PMID: 30319829 DOI: 10.1155/2018/4606259
    Preputial calculus is a relative surgical rarity. It usually happens in elderly men with poor hygiene and uncircumcised penis complicated with phimosis. In the paediatric group, it is usually secondary to phimosis and other urologic and/or neurologic anomalies. Surgical treatment is the mainstay of treatment. Herein, we report a 27-year-old gentleman with preputial stone presented with obstructive uropathy and was successfully treated with surgical intervention. To the best of our knowledge, this is the first reported case of the largest preputial stone in Malaysia.
  17. Hui Lian H, Hayati F, Ali AA, Azizan N, Che Ani MF, Suhaili MA, et al.
    Folia Morphol (Warsz), 2018;77(2):400-402.
    PMID: 29064546 DOI: 10.5603/FM.a2017.0097
    We present the case of a 16-year-old boy presented with 2-week episode of wor-sening lower abdominal pain. Clinically, there was a tender palpable mass on the suprapubic region. Ultrasonography showed an absent spleen at its usual area, instead suprapubic mass suggestive of ectopic spleen was identified. An emer-gency laparotomy revealed a congested spleen in the pelvic cavity. Splenectomy was undertaken as it was non-viable. The patient was discharged uneventfully with triple vaccinations. We describe this unique entity with its literature review. (Folia Morphol 2018; 77, 2: 400-402).
  18. Juhari WKW, Ahmad Amin Noordin KB, Zakaria AD, Rahman WFWA, Mokhter WMMWM, Hassan MRA, et al.
    Genes (Basel), 2021 09 20;12(9).
    PMID: 34573430 DOI: 10.3390/genes12091448
    BACKGROUND: This study aimed to identify new genes associated with CRC in patients with normal mismatch repair (MMR) protein expression.

    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.

  19. 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.
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