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  1. Karen-Ng LP, Marhazlinda J, Rahman ZA, Yang YH, Jalil N, Cheong SC, et al.
    Asian Pac J Cancer Prev, 2011;12(5):1161-6.
    PMID: 21875259
    Dietary isothiocyanates (ITCs) found in cruciferous vegetables (Brassica spp.) has been reported to reduce cancer risk by inducing phase II conjugating enzymes, in particular glutathione S-transferases (GSTs). This case-control study was aimed at determining associations between dietary ITCs, GSTs polymorphisms and risk habits (cigarette smoking, alcohol drinking and betel-quid chewing) with oral cancer in 115 cases and 116 controls. Information on dietary ITC intake from cruciferous vegetables was collected via a semi-quantitative food frequency questionnaire (FFQ). Peripheral blood lymphocytes were obtained for genotyping of GSTM1, GSTT1 and GSTP1 using PCR multiplex and PCR-RFLP. Chi-square and logistic regression were performed to determine the association of ITC and GSTs polymorphism and risk of oral cancer. When dietary ITC was categorized into high (greater than/equal to median) and low (less than median) intake, there was no significant difference between cases and control group. Logistic regression yielding odd ratios resulted in no significant association between dietary ITC intake, GSTM1, GSTT1 or GSTP1 genotypes with oral cancer risk overall. However, GSTP1 wild-type genotype was associated with later disease onset in women above 55 years of age (p= 0.017). Among the men above 45 years of age, there was clinical significant difference of 17 years in the age of onset of oral cancer between GSTP1 wild-type + low ITC intake and GSTP1 polymorphism + high ITC intake (p= 0.001). Similar conditions were also seen among men above 45 years of age with risk habits like drinking and chewing as the earlier disease onset associated with GSTP1 polymorphism and high ITC intake (p< 0.001). This study suggests that combination effects between dietary ITCs, GSTP1 polymorphism and risk habits may be associated with the risk of oral cancer and modulate the age of disease onset.
  2. Doss JG, Ghani WMN, Razak IA, Yang YH, Rogers SN, Zain RB
    Int J Oral Maxillofac Surg, 2017 Jun;46(6):687-698.
    PMID: 28318871 DOI: 10.1016/j.ijom.2017.02.1269
    This study aimed to assess changes in oral cancer patients' health-related quality of life (HRQOL) and the impact of disease stage on HRQOL scores. HRQOL data were collected from seven hospital-based centres using the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) version 4.0 instrument. The independent samples t-test, χ(2) test, and paired samples t-test were used to analyse the data. A total of 300 patients were recruited. The most common oral cancer sub-site was tongue and floor of mouth (42.6%). Surgical intervention (41.1%) was the most common treatment modality. Significant differences in ethnicity and treatment modality were observed between early and late stage patients. Pre-treatment HRQOL scores were significantly lower for late than early stage patients. At 1 month post-treatment, the functional and head and neck domains and the FACT-H&N (TOI) summary scores showed significant deterioration in both early and late stage patients. In contrast, the emotional domain showed a significant improvement for early and late stage patients at 1, 3, and 6 months post-treatment. Although HRQOL deterioration was still observed among early and late stage patients at 6 months post-treatment, this was not statistically significant. In conclusion, advanced disease is associated with poorer HRQOL. Although ethnic differences were observed across different disease stages, the influence of ethnicity on patient HRQOL was not evident in this study.
  3. Ramanathan A, Zaini ZM, Ghani WMN, Wong GR, Zainuddin NI, Yang YH, et al.
    Oral Dis, 2024 Mar 15.
    PMID: 38488212 DOI: 10.1111/odi.14927
    OBJECTIVE: This study evaluated the effectiveness of face-to-face (F2F) and online OralDETECT training programme in enhancing early detection skills for oral cancer.

    METHODS: A total of 328 final-year dental students were trained across six cohorts. Three cohorts (175 students) received F2F training from the academic years 2016/2017 to 2018/2019, and the remaining three (153 students) underwent online training during the Covid-19 pandemic from 2019/2020 to 2021/2022. Participant scores were analysed using the Wilcoxon signed rank test, the Mann-Whitney test, Cohen's d effect size, and multiple linear regression.

    RESULTS: Both F2F and online training showed increases in mean scores from pre-test to post-test 3: from 67.66 ± 11.81 to 92.06 ± 5.27 and 75.89 ± 11.03 to 90.95 ± 5.22, respectively. Comparison between F2F and online methods revealed significant differences in mean scores with large effect sizes at the pre-test stage (p 

  4. Ghani WM, Razak IA, Yang YH, Talib NA, Ikeda N, Axell T, et al.
    BMC Public Health, 2012;12:207.
    PMID: 22429627 DOI: 10.1186/1471-2458-12-207
    BACKGROUND: Tobacco consumption peak in developed countries has passed, however, it is on the increase in many developing countries. Apart from cigarettes, consumption of local hand-rolled cigarettes such as bidi and rokok daun are prevalent in specific communities. Although factors associated with smoking initiation and cessation has been investigated elsewhere, the only available data for Malaysia is on prevalence. This study aims to investigate factors associated with smoking initiation and cessation which is imperative in designing intervention programs.
    METHODS: Data were collected from 11,697 adults by trained recording clerks on sociodemographic characteristics, practice of other risk habit and details of smoking such as type, duration and frequency. Smoking commencement and cessation were analyzed using the Kaplan-Meier estimates and log-rank tests. Univariate and multivariate Cox proportional hazard regression models were used to calculate the hazard rate ratios.
    RESULTS: Males had a much higher prevalence of the habit (61.7%) as compared to females (5.8%). Cessation was found to be most common among the Chinese and those regularly consuming alcoholic beverages. Kaplan-Meier plot shows that although males are more likely to start smoking, females are found to be less likely to stop. History of betel quid chewing and alcohol consumption significantly increase the likelihood of commencement (p < 0.0001), while cessation was least likely among Indians, current quid chewers and kretek users (p < 0.01).
    CONCLUSIONS: Gender, ethnicity, history of quid chewing and alcohol consumption have been found to be important factors in smoking commencement; while ethnicity, betel quid chewing and type of tobacco smoked influences cessation.
  5. Ghani WM, Razak IA, Yang YH, Talib NA, Ikeda N, Axell T, et al.
    BMC Public Health, 2011;11:82.
    PMID: 21294919 DOI: 10.1186/1471-2458-11-82
    Betel quid chewing is a common habit widely practiced in Southern Asian populations. However, variations are seen in the content of a betel quid across the different countries. Factors associated with commencement and cessation of this habit has been numerously studied. Unfortunately, data on Malaysian population is non-existent. This study aims to determine the factors associated with the inception and also cessation of betel quid chewing behaviour among Malaysian adults.
  6. Gunjal S, Pateel DGS, Yang YH, Doss JG, Bilal S, Maling TH, et al.
    Subst Use Misuse, 2020;55(9):1533-1544.
    PMID: 32569533 DOI: 10.1080/10826084.2019.1657149
    Background: Areca nut (AN) and betel quid (BQ) chewing are ancient practices followed by an extensive proportion of the world's population. These practices are endemic in larger parts of South and Southeast Asia and selected Western Pacific countries. The prevalence of these habits varies across regions, age, gender, cultural practice, and socioeconomic status groups. Considerable variations exist between countries with respect to prevention/intervention programs, and policy guidelines of BQ usage. Objectives: (1) To provide an overview of the BQ chewing prevalence, practices, preventive interventions and policies in selected Asian and Western Pacific countries. (2) To explore the different terminologies associated with BQ use. Method: A narrative review of the current literature related to BQ, AN, and oral cancer was conducted by searching PUBMED, CINAHL, and GOOGLE databases. Results: The literature review revealed that the prevalence of BQ was found to be highest in Papua New Guinea, followed by Bangladesh, India, Pakistan, Myanmar and Sri Lanka. While, Cambodia, Malaysia, Indonesia and Taiwan had comparatively lower prevalence. Smokeless tobacco, BQ with tobacco, BQ without tobacco, AN were some of the terminologies used for BQ in various studies. Conclusions: The prevalence, and the interventional policies related to BQ and AN chewing habits varies widely among the selected countries. With the increasing awareness and association of BQ with oral cancer, there is a need to have better awareness, prevention and interventional strategies in place. We also found considerable variation in the use of terminologies associated with BQ.
  7. Wong GR, Ha KO, Himratul-Aznita WH, Yang YH, Wan Mustafa WM, Yuen KM, et al.
    Oral Dis, 2014 Nov;20(8):762-7.
    PMID: 24320099 DOI: 10.1111/odi.12218
    The objective of the study was to determine the prevalence of HPV seropositivity among patients with oral squamous cell carcinoma (OSCC) and healthy individuals and to correlate the association between HPV 16 seropositivity and risk of OSCC.
  8. Siow MY, Ng LP, Vincent-Chong VK, Jamaludin M, Abraham MT, Abdul Rahman ZA, et al.
    Oral Dis, 2014 May;20(4):345-51.
    PMID: 23651447 DOI: 10.1111/odi.12118
    To identify differentially expressed miRNA between oral squamous cell carcinoma (OSCC) and non-cancer (NC) and to associate these with clinico-pathological parameters.
  9. Saleh A, Yang YH, Wan Abd Ghani WM, Abdullah N, Doss JG, Navonil R, et al.
    Asian Pac J Cancer Prev, 2012;13(4):1217-24.
    PMID: 22799308
    BACKGROUND AND AIM: Less than 50% of oral cancer cases are diagnosed at early stages of the disease and this is in part due to poor awareness and lack of knowledge on the signs and symptoms of oral cancer. This study sought to measure the baseline awareness of oral cancer in Malaysia and aimed to increase public awareness and knowledge of oral cancer using a mass media campaign.

    METHODS: Baseline awareness and impact of the campaign was measured using self-administered questionnaires sent via email to individuals. The campaign was aired on two national television channels and the reach was monitored through an independent programme monitoring system.

    RESULTS: 78.2% of respondents had heard of oral cancer, and this increased significantly after the campaign. However, the ability to recognize signs and symptoms remains unchanged. We found that the level of awareness differed between the distinct ethnic subgroups and the reach of the campaign was not uniform across all ethnicities.

    CONCLUSION: This substantial study to measure the oral cancer awareness in Malaysia provides important baseline data for the planning of public health policies. Despite encouraging evidence that a mass media campaign could increase the awareness of oral cancer, further research is required to address the acceptability, comprehensiveness and effectiveness. Furthermore, different campaign approaches may be required for specific ethnic groups in a multi-ethnic country such as Malaysia.

  10. Zanaruddin SN, Saleh A, Yang YH, Hamid S, Mustafa WM, Khairul Bariah AA, et al.
    Hum Pathol, 2013 Mar;44(3):417-26.
    PMID: 23026198 DOI: 10.1016/j.humpath.2012.06.007
    The presence of lymph node (LN) metastasis significantly affects the survival of patients with oral squamous cell carcinoma (OSCC). Successful detection and removal of positive LNs are crucial in the treatment of this disease. Current evaluation methods still have their limitations in detecting the presence of tumor cells in the LNs, where up to a third of clinically diagnosed metastasis-negative (N0) patients actually have metastasis-positive LNs in the neck. We developed a molecular signature in the primary tumor that could predict LN metastasis in OSCC. A total of 211 cores from 55 individuals were included in the study. Eleven proteins were evaluated using immunohistochemical analysis in a tissue microarray. Of the 11 biomarkers evaluated using receiver operating curve analysis, epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (HER-2/neu), laminin, gamma 2 (LAMC2), and ras homolog family member C (RHOC) were found to be significantly associated with the presence of LN metastasis. Unsupervised hierarchical clustering-demonstrated expression patterns of these 4 proteins could be used to differentiate specimens that have positive LN metastasis from those that are negative for LN metastasis. Collectively, EGFR, HER-2/neu, LAMC2, and RHOC have a specificity of 87.5% and a sensitivity of 70%, with a prognostic accuracy of 83.4% for LN metastasis. We also demonstrated that the LN signature could independently predict disease-specific survival (P = .036). The 4-protein LN signature validated in an independent set of samples strongly suggests that it could reliably distinguish patients with LN metastasis from those who were metastasis-free and therefore could be a prognostic tool for the management of patients with OSCC.
  11. Hamid S, Yang YH, Peng KN, Ismail SM, Zain RB, Lim KP, et al.
    Oral Oncol, 2009 Jun;45(6):496-500.
    PMID: 18804411 DOI: 10.1016/j.oraloncology.2008.06.003
    The MDM2 SNP309 has been associated with increased expression of the protein which could suppress p53 function, and has been shown to modulate risk to cancer. We have previously shown that overexpression of MDM2 is a common event in oral cancers. In the present study, we determined the association between the MDM2 SNP309 polymorphism and oral cancer in 207 oral cancer patients and 116 normal subjects. We genotyped the MDM2 SNP309 by PCR-RFLP. Logistic regression was adapted to calculate odds ratios for MDM2 SNP309 polymorphism from univariate and multivariable adjusted models. Our results suggest that MDM2 SNP309 does not confer increased risk to oral cancer (OR=1.55, 95% CI=0.77-3.11). However, the GG/TG genotype was associated with later disease onset in women above 55 years of age. Collectively, our data suggests that MDM2 SNP309 may modulate the risk to oral cancer and is a modifier of the age at oral cancer onset in women above the age of 55 years.
  12. Zain RB, Pateel DGS, Ramanathan A, Kallarakkal TG, Wong GR, Yang YH, et al.
    J Cancer Educ, 2020 Aug 21.
    PMID: 32821988 DOI: 10.1007/s13187-020-01814-1
    Early diagnosis of oral cancer results in less aggressive treatment and improves the quality of life and overall 5-year survival rate. Well-trained dental professionals can play a crucial role in the early detection of oral cancers. The present study aims to determine the effectiveness of the training program "OralDETECT", a spaced repetitive, test-enhanced learning tool with a corrective feedback mechanism for early detection of oral cancer. Thirty-two dentists and 259 dental students from three Malaysian dental schools were involved in this study. All participants were trained and calibrated to recognize oral potentially malignant disorders (OPMD) and oral cancer using "OralDETECT", which is comprised of a series of pre-test, lecture, post-tests and review sessions. The percentage of correct answers (scores) for each test given by the participants was calculated and analysed using a paired t test. It was found that the overall percentage of diagnostic accuracy for both dental professionals and student groups increased to above 80% from the pre-tests to the final post-tests. There was a significant improvement in overall scores between the pre-tests and all three post-tests for the dental professional groups and the student groups. The diagnostic accuracy for individual OPMD and lesions suspicious of oral cancer also increased to above 80% for both groups. The results of our study demonstrate that the "OralDETECT" is an efficient and effective competency tool which can be used to train dental professionals and students for the early detection of OPMD and oral cancer.
  13. Ghani WMN, Razak IA, Doss JG, Yang YH, Rahman ZAA, Ismail SM, et al.
    Oral Dis, 2019 Mar;25(2):447-455.
    PMID: 30350902 DOI: 10.1111/odi.12995
    OBJECTIVE: To elucidate ethnic variations in the practice of oral cancer risk habits in a selected Malaysian population.

    METHODS: This retrospective case-control study involves 790 cases of cancers of the oral cavity and 450 controls presenting with non-malignant oral diseases, recruited from seven hospital-based centres nationwide. Data on risk habits (smoking, drinking, chewing) were obtained using a structured questionnaire via face-to-face interviews. Multiple logistic regression was used to determine association between risk habits and oral cancer risk; chi-square test was used to assess association between risk habits and ethnicity. Population attributable risks were calculated for all habits.

    RESULTS: Except for alcohol consumption, increased risk was observed for all habits; the highest risk was for smoking + chewing + drinking (aOR 22.37 95% CI 5.06, 98.95). Significant ethnic differences were observed in the practice of habits. The most common habit among Malays was smoking (24.2%); smoking + drinking were most common among Chinese (16.8%), whereas chewing was the most prevalent among Indians (45.2%) and Indigenous people (24.8%). Cessation of chewing, smoking and drinking is estimated to reduce cancer incidence by 22.6%, 8.5% and 6.9%, respectively.

    CONCLUSION: Ethnic variations in the practice of oral cancer risk habits are evident. Betel quid chewing is the biggest attributable factor for this population.

  14. Athirajan V, Razak IA, Thurairajah N, Ghani WM, Ching HN, Yang YH, et al.
    Asian Pac J Cancer Prev, 2014;15(19):8183-9.
    PMID: 25339003
    BACKGROUND: A comparative cross-sectional study involving oral cancer patients and healthy individuals was designed to investigate associations between retinol, α-tocopherol and β-carotene with the risk of oral cancer.

    MATERIALS AND METHODS: This study included a total of 240 matched cases and controls where subjects were selected from the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). Retinol, α-tocopherol and β-carotene levels and intake were examined by high-performance liquid chromatography (HPLC) and food frequency questionnaire (FFQ) respectively.

    RESULTS: It was found that results from the two methods applied did not correlate, so that further analysis was done using the HPLC method utilising blood serum. Serum levels of retinol and α-tocopherol among cases (0.177±0.081, 1.649±1.670μg/ml) were significantly lower than in controls (0.264±0.137, 3.225±2.054μg/ml) (p<0.005). Although serum level of β-carotene among cases (0.106±0.159 μg/ml) were lower compared to controls (0.134±0.131μg/ml), statistical significance was not observed. Logistic regression analysis showed that high serum level of retinol (OR=0.501, 95% CI=0.254-0.992, p<0.05) and α-tocopherol (OR=0.184, 95% CI=0.091-0.370, p<0.05) was significantly related to lower risk of oral cancer, whereas no relationship was observed between β-carotene and oral cancer risk.

    CONCLUSIONS: High serum levels of retinol and α-tocopherol confer protection against oral cancer risk.

  15. Vincent-Chong VK, Salahshourifar I, Karen-Ng LP, Siow MY, Kallarakkal TG, Ramanathan A, et al.
    ScientificWorldJournal, 2014;2014:897523.
    PMID: 25401159 DOI: 10.1155/2014/897523
    Matrix metalloproteinase 13 (MMP13) plays a central role in the MMP activation cascade that enables degradation of the extracellular matrix and basement membranes, and it is identified as a potential driver in oral carcinogenesis. Therefore, this study aims to determine the copy number, mRNA, and protein expression of MMP13 in oral squamous cell carcinoma (OSCC) and to associate these expressions with clinicopathological parameters. Copy number, mRNA, and protein expression analysis of MMP13 were determined using real-time quantitative PCR and immunohistochemistry methods in OSCC samples. The correlations between MMP13 expressions and clinicopathological parameters were evaluated, and the significance of MMP13 as a prognostic factor was determined. Despite discrepancies between gene amplification and mRNA and protein overexpression rates, OSCC cases showed high amplification of MMP13 and overexpression of MMP13 at both mRNA and protein levels. High level of MMP13 protein expression showed a significant correlation with lymph node metastasis (P = 0.011) and tumor staging (P = 0.002). Multivariate Cox regression model analysis revealed that high level of mRNA and protein expression of MMP13 were significantly associated with poor prognosis (P < 0.050). Taken together, these observations indicate that the MMP13 protein overexpression could be considered as a prognostic marker of OSCC.
  16. Ghani WMN, Ramanathan A, Prime SS, Yang YH, Razak IA, Abdul Rahman ZA, et al.
    Cancer Invest, 2019;37(7):275-287.
    PMID: 31307249 DOI: 10.1080/07357907.2019.1635614
    Previous studies found that ethnicity influences oral cancer patients' survival; however, most studies were limited to certain ethnic groups particularly from the West, thus of limited relevance to Asians where the disease is most prevalent. We investigated the relationship between ethnicity and patient survival in multi-racial Malaysia. 5-year survival rate was 40.9%. No statistically significant difference was observed in survival between Malays, Chinese, Indians and Indigenous peoples (45.7%, 44.0%, 41.3%, 27.7% respectively). Increased tumor size, lymph node involvement and advanced tumor were predictive of poor survival. We conclude that ethnicity has no effect on survival or its prognostic indicators.
  17. Vincent-Chong VK, Karen-Ng LP, Abdul Rahman ZA, Yang YH, Anwar A, Zakaria Z, et al.
    Head Neck, 2014 Sep;36(9):1268-1278.
    PMID: 31615169 DOI: 10.1002/hed.23448
    BACKGROUND: The purpose of this study was to investigate the cause of behavioral difference between tongue and cheek squamous cell carcinomas (SCCs) by verifying the copy number alterations (CNAs).

    METHODS: Array comparative genomic hybridization (aCGH) was used to profile unique deletions and amplifications that are involved with tongue and cheek SCC, respectively. This was followed by pathway analysis relating to CNA genes from both sites.

    RESULTS: The most frequently amplified regions in tongue SCC were 4p16.3, 11q13.4, and 13q34; whereas the most frequently deleted region was 19p12. For cheek SCC, the most frequently amplified region was identified on chromosome 9p24.1-9p23; whereas the most common deleted region was located on chromosome 8p23.1. Further analysis revealed that the most significant unique pathway related to tongue and cheek SCCs was the cytoskeleton remodeling and immune response effect on the macrophage differentiation pathway.

    CONCLUSION: This study has showed the different genetic profiles and biological pathways between tongue and cheek SCCs. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1268-1278, 2014.

  18. Man KKC, Shao SC, Chaiyakunapruk N, Dilokthornsakul P, Kubota K, Li J, et al.
    Eur Child Adolesc Psychiatry, 2022 Jan;31(1):99-120.
    PMID: 33185773 DOI: 10.1007/s00787-020-01674-6
    It is known that younger patients treated with antipsychotics are at increased risk of metabolic events; however, it is unknown how this risk varies according to ethnicity, the class of antipsychotic and the specific product used, and by age group. We conducted a multinational sequence symmetry study in Asian populations (Hong Kong, Japan, Korea, Taiwan and Thailand) and non-Asian populations (Australia and Denmark) to evaluate the metabolic events associated with antipsychotics in both Asian and non-Asian populations, for typical and atypical antipsychotics, and by the subgroups of children and adolescents, and young adults. Patients aged 6-30 years newly initiating oral antipsychotic drugs were included. We defined a composite outcome for metabolic events which included dyslipidemia, hypertension and hyperglycemia. We calculated the sequence ratio (SR) by dividing the number of people for whom a medicine for one of the outcome events was initiated within a 12-month period after antipsychotic initiation by the number before antipsychotic initiation. This study included 346,904 antipsychotic initiators across seven countries. Antipsychotic use was associated with an increased risk of composite metabolic events with a pooled adjusted SR (ASR) of 1.22 (95% CI 1.00-1.50). Pooled ASRs were similar between Asian (ASR, 1.22; 95% CI 0.88-1.70) and non-Asian populations (ASR, 1.22; 95% CI 1.04-1.43). The pooled ASR for typical and atypical antipsychotics was 0.98 (95% CI 0.85-1.12) and 1.24 (95% CI 0.97-1.59), respectively. No difference was observed in the relative effect in children and adolescents compared to young adults. The risk of metabolic events associated with antipsychotics use was similar in magnitude in Asian and non-Asian populations despite the marked difference in drug utilization patterns.
  19. Rajendran S, Lim JH, Yogalingam K, Kallarakkal TG, Zain RB, Jayasinghe RD, et al.
    Oral Dis, 2023 Jul;29(5):2230-2238.
    PMID: 35398971 DOI: 10.1111/odi.14206
    OBJECTIVE: To describe the development of a platform for image collection and annotation that resulted in a multi-sourced international image dataset of oral lesions to facilitate the development of automated lesion classification algorithms.

    MATERIALS AND METHODS: We developed a web-interface, hosted on a web server to collect oral lesions images from international partners. Further, we developed a customised annotation tool, also a web-interface for systematic annotation of images to build a rich clinically labelled dataset. We evaluated the sensitivities comparing referral decisions through the annotation process with the clinical diagnosis of the lesions.

    RESULTS: The image repository hosts 2474 images of oral lesions consisting of oral cancer, oral potentially malignant disorders and other oral lesions that were collected through MeMoSA® UPLOAD. Eight-hundred images were annotated by seven oral medicine specialists on MeMoSA® ANNOTATE, to mark the lesion and to collect clinical labels. The sensitivity in referral decision for all lesions that required a referral for cancer management/surveillance was moderate to high depending on the type of lesion (64.3%-100%).

    CONCLUSION: This is the first description of a database with clinically labelled oral lesions. This database could accelerate the improvement of AI algorithms that can promote the early detection of high-risk oral lesions.

  20. Vincent-Chong VK, Anwar A, Karen-Ng LP, Cheong SC, Yang YH, Pradeep PJ, et al.
    PLoS One, 2013;8(2):e54705.
    PMID: 23405089 DOI: 10.1371/journal.pone.0054705
    Despite the advances in diagnosis and treatment of oral squamous cell carcinoma (OSCC), mortality and morbidity rates have not improved over the past decade. A major drawback in diagnosis and treatment of OSCC is the lack of knowledge relating to how genetic instability in oral cancer genomes affects oral carcinogenesis. Hence, the key aim of this study was to identify copy number alterations (CNAs) that may be cancer associated in OSCC using high-resolution array comparative genomic hybridization (aCGH). To our knowledge this is the first study to use ultra-high density aCGH microarrays to profile a large number of OSCC genomes (n = 46). The most frequently amplified CNAs were located on chromosome 11q11(52%), 2p22.3(52%), 1q21.3-q22(54%), 6p21.32(59%), 20p13(61%), 7q34(52% and 72%),8p11.23-p11.22(80%), 8q11.1-q24.4(54%), 9q13-q34.3(54%), 11q23.3-q25(57%); 14q21.3-q31.1(54%); 14q31.3-q32.33(57%), 20p13-p12.3(54%) and 20q11.21-q13.33(52%). The most frequently deleted chromosome region was located on 3q26.1 (54%). In order to verify the CNAs from aCGH using quantitative polymerase chain reaction (qPCR), the three top most amplified regions and their associated genes, namely ADAM5P (8p11.23-p11.22), MGAM (7q34) and SIRPB1 (20p13.1), were selected in this study. The ADAM5P locus was found to be amplified in 39 samples and deleted in one; MGAM (24 amplifications and 3 deletions); and SIRPB1 (12 amplifications, others undetermined). On the basis of putative cancer-related annotations, two genes, namely ADAM metallopeptidase domain 9 (ADAM9) and maltase-glucoamylase alpha-glucosidase (MGAM), that mapped to CNA regions were selected for further evaluation of their mRNA expression using reverse transcriptase qPCR. The over-expression of MGAM was confirmed with a 6.6 fold increase in expression at the mRNA level whereas the fold change in ADAM9 demonstrated a 1.6 fold increase. This study has identified significant regions in the OSCC genome that were amplified and resulted in consequent over-expression of the MGAM and ADAM9 genes that may be utilized as biological markers for OSCC.
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