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Laser capture microdissection with genome-wide expression profiling displayed gene expression signatures in endometrioid endometrial cancer

Mokhtar NM, Ramzi NH, Yin-Ling W, Rose IM, Hatta Mohd Dali AZ, Jamal R

Cancer Invest, 2012 Feb;30(2):156-64.
PMID: 22122087 DOI: 10.3109/07357907.2011.633290

This research determined genes contributing to the pathogenesis of endometrioid endometrial cancer (EEC). Eight pairs of microdissected EEC samples matched with normal glandular epithelium were analyzed using microarray. Unsupervised analysis identified 162 transcripts (58 up- and 104 down-regulated) that were differentially expressed (p < .01, fold change ≥ 1.5) between both groups. Quantitative real-time polymerase chain reaction (qPCR) validated the genes of interest: SLC7A5, SATB1, H19, and ZAK (p < .05). Pathway analysis revealed genes involved in acid amino transport, translation, and chromatin remodeling (p < .05). Laser capture microdissection (LCM) followed by microarray enabled precise assessment of homogeneous cell population and identified putative genes for endometrial carcinogenesis.
Association of genetic and non-genetic risk factors with the development of prostate cancer in Malaysian men

Munretnam K, Alex L, Ramzi NH, Chahil JK, Kavitha IS, Hashim NA, et al.

Mol Biol Rep, 2014;41(4):2501-8.
PMID: 24443231 DOI: 10.1007/s11033-014-3107-8

There is growing global interest to stratify men into different levels of risk to developing prostate cancer, thus it is important to identify common genetic variants that confer the risk. Although many studies have identified more than a dozen common genetic variants which are highly associated with prostate cancer, none have been done in Malaysian population. To determine the association of such variants in Malaysian men with prostate cancer, we evaluated a panel of 768 SNPs found previously associated with various cancers which also included the prostate specific SNPs in a population based case control study (51 case subjects with prostate cancer and 51 control subjects) in Malaysian men of Malay, Chinese and Indian ethnicity. We identified 21 SNPs significantly associated with prostate cancer. Among these, 12 SNPs were strongly associated with increased risk of prostate cancer while remaining nine SNPs were associated with reduced risk. However, data analysis based on ethnic stratification led to only five SNPs in Malays and 3 SNPs in Chinese which remained significant. This could be due to small sample size in each ethnic group. Significant non-genetic risk factors were also identified for their association with prostate cancer. Our study is the first to investigate the involvement of multiple variants towards susceptibility for PC in Malaysian men using genotyping approach. Identified SNPs and non-genetic risk factors have a significant association with prostate cancer.
Identification of genetic and non-genetic risk factors for nasopharyngeal carcinoma in a Southeast Asian population

Nor Hashim NA, Ramzi NH, Velapasamy S, Alex L, Chahil JK, Lye SH, et al.

Asian Pac J Cancer Prev, 2012;13(12):6005-10.
PMID: 23464394

BACKGROUND: Nasopharyngeal carcinoma (NPC) is endemic in Southern Chinese and Southeast Asian populations. Geographical and ethnic clustering of the cancer is due to genetic, environmental, and lifestyle risk factors. This case-control study aimed to identify or confirm both genetic and non-genetic risk factors for NPC in one of the endemic countries, Malaysia.
MATERIALS AND METHOD: A panel of 768 single-nucleotide polymorphisms (SNPs) previously associated with various cancers and known non-genetic risk factors for NPC were selected and analyzed for their associations with NPC in a case-control study.
RESULTS: Statistical analysis identified 40 SNPs associated with NPC risk in our population, including 5 documented previously by genome-wide association studies (GWAS) and other case-control studies; the associations of the remaining 35 SNPs with NPC were novel. In addition, consistent with previous studies, exposure to occupational hazards, overconsumption of salt-cured foods, red meat, as well as low intake of fruits and vegetables were also associated with NPC risk.
CONCLUSIONS: In short, this study confirmed and/or identified genetic, environmental and dietary risk factors associated with NPC susceptibility in a Southeast Asian population.
Fulltext Genetic polymorphisms associated with breast cancer in malaysian cohort

Chahil JK, Munretnam K, Samsudin N, Lye SH, Hashim NA, Ramzi NH, et al.

Indian J Clin Biochem, 2015 Apr;30(2):134-9.
PMID: 25883419 DOI: 10.1007/s12291-013-0414-0

Genome-wide association studies have discovered multiple single nucleotide polymorphisms (SNPs) associated with the risk of common diseases. The objective of this study was to demonstrate the replication of previously published SNPs that showed statistical significance for breast cancer in the Malaysian population. In this case-control study, 80 subjects for each group were recruited from various hospitals in Malaysia. A total of 768 SNPs were genotyped and analyzed to distinguish risk and protective alleles. A total of three SNPs were found to be associated with increased risk of breast cancer while six SNPs showed protective effect. All nine were statistically significant SNPs (p ≤ 0.01), five SNPs from previous studies were successfully replicated in our study. Significant modifiable (diet) and non-modifiable (family history of breast cancer in first degree relative) risk factors were also observed. We identified nine SNPs from this study to be either conferring susceptibility or protection to breast cancer which may serve as potential markers in risk prediction.
Influences of multiple genetic polymorphisms on ovarian cancer risk in Malaysia

Velapasamy S, Alex L, Chahil JK, Lye SH, Munretnam K, Hashim NA, et al.

Genet Test Mol Biomarkers, 2013 Jan;17(1):62-8.
PMID: 23113749 DOI: 10.1089/gtmb.2012.0223

The identification of high-risk individuals can help to improve early cancer detection and patient survival. Risk assessment, however, can only be accomplished if the risk factors are known. To date, the genetic risk factors for ovarian cancer, other than mutations in the BRCA1/2 genes, have never been systematically explored in Malaysia. The present study aims to identify from a panel of cancer-associated single-nucleotide polymorphisms (SNPs), those associated with ovarian cancer risk in Malaysia.
Fulltext A novel strategy for community screening of SARS-CoV-2 (COVID-19): Sample pooling method

Lim KL, Johari NA, Wong ST, Khaw LT, Tan BK, Chan KK, et al.

PLoS One, 2020;15(8):e0238417.
PMID: 32857823 DOI: 10.1371/journal.pone.0238417

The rapid global spread of the coronavirus disease (COVID-19) has inflicted significant health and socioeconomic burden on affected countries. As positive cases continued to rise in Malaysia, public health laboratories experienced an overwhelming demand for COVID-19 screening. The confirmation of positive cases of COVID-19 has solely been based on the detection of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) using real-time reverse transcription polymerase chain reaction (qRT-PCR). In efforts to increase the cost-effectiveness and efficiency of COVID-19 screening, we evaluated the feasibility of pooling clinical Nasopharyngeal/Oropharyngeal (NP/OP) swab specimens during nucleic acid extraction without a reduction in sensitivity of qRT-PCR. Pools of 10 specimens were extracted and subsequently tested by qRT-PCR according to the WHO-Charité protocol. We demonstrated that the sample pooling method showed no loss of sensitivity. The effectiveness of the pooled testing strategy was evaluated on both retrospective and prospective samples, and the results showed a similar detection sensitivity compared to testing individual sample alone. This study demonstrates the feasibility of using a pooled testing strategy to increase testing capacity and conserve resources, especially when there is a high demand for disease testing.
Fulltext COVID-19 Sample Pooling: From RNA Extraction to Quantitative Real-time RT-PCR

Voon K, Johari NA, Lim KL, Wong ST, Khaw LT, Wong SF, et al.

Bio Protoc, 2021 May 05;11(9):e4005.
PMID: 34124305 DOI: 10.21769/BioProtoc.4005

The COVID-19 pandemic requires mass screening to identify those infected for isolation and quarantine. Individually screening large populations for the novel pathogen, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is costly and requires a lot of resources. Sample pooling methods improve the efficiency of mass screening and consume less reagents by increasing the capacity of testing and reducing the number of experiments performed, and are therefore especially suitable for under-developed countries with limited resources. Here, we propose a simple, reliable pooling strategy for COVID-19 testing using clinical nasopharyngeal (NP) and/or oropharyngeal (OP) swabs. The strategy includes the pooling of 10 NP/OP swabs for extraction and subsequent testing via quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR), and may also be applied to the screening of other pathogens.
Depression mediates the relationship between alexithymia and obesity in the Northern Finland Birth Cohort 1966 (NFBC1966)

Ramzi NH, Auvinen J, Veijola J, Miettunen J, Ala-Mursula L, Sebert S, et al.

J Affect Disord, 2023 Jun 15;331:1-7.
PMID: 36933669 DOI: 10.1016/j.jad.2023.03.026

BACKGROUND: The fact that a complex relationship exists between alexithymia and body mass index (BMI) is well established, but the underlying mechanisms remain poorly understood. Here, we explore the relationship between alexithymia and depressive symptoms in relation to adiposity measures, including the direct and indirect effect of alexithymia and depressive symptoms on obesity over a 15-year time-period, in the Northern Finland Birth Cohort 1966 (NFBC1966).
METHODS: The study included individuals from the Northern Finland Birth Cohort 1966 (NFBC1966) who had available data for adiposity measures (body mass index and waist-to-hip ratio), alexithymia (measured by the 20-Item Toronto Alexithymia Scale: TAS-20), depressive symptoms (measured by the 13-item depression subscale of Hopkins Symptom Checklist: HSCL-13) at age of 31 years (n = 4773) and 46 years (n = 4431). Pearson's (r) correlation, and multiple linear regression were used to investigate the relationships between alexithymia, depressive symptoms, and adiposity measures. The potential mediating role of depressive symptoms was examined via Hayes' procedure (PROCESS).
RESULTS: Positive correlations were confirmed between adiposity measures (BMI and WHR) and the TAS-20 score (and its subscale), but not between obesity and HSCL-13 score. The strongest correlation was between the DIF (difficulty identifying feelings) subscale of the TAS-20 and HSCL-13 at both time points (31 y: r(3013) = 0.41, p
Fulltext Role of genetic & environment risk factors in the aetiology of colorectal cancer in Malaysia

Ramzi NH, Chahil JK, Lye SH, Munretnam K, Sahadevappa KI, Velapasamy S, et al.

Indian J Med Res, 2014 Jun;139(6):873-82.
PMID: 25109722

Colorectal cancer (CRC) is second only to breast cancer as the leading cause of cancer-related deaths in Malaysia. In the Asia-Pacific area, it is the highest emerging gastrointestinal cancer. The aim of this study was to identify single nucleotide polymorphisms (SNPs) and environmental factors associated with CRC risk in Malaysia from a panel of cancer associated SNPs.