Papers by Shing Cheng Tan
Cancers, Apr 26, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Pharmaceuticals
Merkel cell carcinoma (MCC) is a rare form of aggressive skin cancer mainly caused by Merkel cell... more Merkel cell carcinoma (MCC) is a rare form of aggressive skin cancer mainly caused by Merkel cell polyomavirus (MCPyV). Most MCC tumors express MCPyV large T (LT) antigens and play an important role in the growth-promoting activities of oncoproteins. Truncated LT promotes tumorigenicity as well as host cell proliferation by activating the viral replication machinery, and inhibition of this protein in humans drastically lowers cellular growth linked to the corresponding cancer. Our study was designed with the aim of identifying small molecular-like natural antiviral candidates that are able to inhibit the proliferation of malignant tumors, especially those that are aggressive, by blocking the activity of viral LT protein. To identify potential compounds against the target protein, a computational drug design including molecular docking, ADME (absorption, distribution, metabolism, and excretion), toxicity, molecular dynamics (MD) simulation, and molecular mechanics generalized Born su...
Gynecologic and Obstetric Investigation, 2019
Dear Editor, I read with great interest an article in Gynecologic and Obstetric Investigation, wh... more Dear Editor, I read with great interest an article in Gynecologic and Obstetric Investigation, which examined the correlation between Chk1 expression and malignant progression of cervical lesions [1]. I would like to congratulate the authors for their comprehensive work. However, upon closer examination of the study methodology, I would like to record my observations about the choice of reference gene in their gene expression analysis, which may potentially lead to misleading conclusions. In their work, Lin and Chen [1] normalized their qRT-PCR data to GAPDH, a well-known housekeeping gene. This is not an uncommon practice in gene expression analyses, as it is often assumed that the expression of housekeeping genes is constant in all biological settings. However, more recent studies have demonstrated that the expression of commonly used housekeeping genes, including but not limited to GAPDH, actually fluctuates greatly across different biological conditions [2]. It is also worthy of mention that there is no single universal reference genes that can be used for all cell or tissue types [3]. Therefore, optimal reference genes must be carefully determined for each experimental condition. In cervical tissues, our previous work has identified several stably expressed genes that can be used for normalizing qRT-PCR data, including PUM1, YWHAZ and RPLP0 [4]. Ironically, we also observed that the expression stability of GAPDH in cervical tissues ranked 22nd out of 27 candidate genes analyzed, which provided an indication that the use of GAPDH for normalizing gene expression data in cervical tissues was not appropriate and might lead to questionable data interpretation. Take Lin and Chen [1] gene expression data for example; the authors concluded that Chk1 expression increased from normal cervical tissues to pre-cancerous neoplasia and finally to cervical cancer. This conclusion was based on the assumption that GAPDH expression was unchanged throughout the malignant progression of the cervix. However, if this unproven assumption was wrong (i.e., if GAPDH expression actually decreased as cervical cells progressed from normalcy to malignancy), the authors could observe the same data trend even if Chk1 expression remained constant, or even decreased, throughout cervical progression. In addition to the choice of reference gene, the number of reference genes used could also influence the validity of gene expression studies. Lin and Chen [1] normalized their qRT-PCR to a single gene. By current standards, however, the use of a single reference gene for normalizing gene expression data is not acceptable, unless strong and adequate justifications are given [3]. There are a few methods that can be used to determine how many reference genes should be included, notably the pairwise variation method [5]. In conclusion, the choice and number of reference genes should be carefully determined before they are used for normalizing qRT-PCR data. These are highly crucial but frequently neglected aspects in gene expression analyses. It would be interesting to see whether normalizing Lin and Chen [1] data to empirically determined reference genes would lead to the same conclusion.
The Journal of Gene Medicine, 2018
Aims: Colorectal cancer is a leading form of cancer in both males and females. Early detection of... more Aims: Colorectal cancer is a leading form of cancer in both males and females. Early detection of individuals at risk of colorectal cancer allows proper treatment and management of the disease to be implemented, which can potentially reduce the burden of colorectal cancer incidence, morbidity and mortality. In recent years, the role of genetic susceptibility factors in mediating predisposition to colorectal cancer has become more and more apparent. This review comprehensively consolidates the recent progresses in the identification of high-frequency, lowpenetrance genetic polymorphisms associated with colorectal cancer. Discussion: The overwhelming amount of genetic epidemiology data generated over the past decades has made it difficult for one to assimilate the information and determine the exact genetic polymorphisms that can potentially be used as biomarkers for colorectal cancer. This review summarizes, based primarily on results from meta-analyses, the current understandings in the search of colorectal cancer-associated genetic polymorphisms, and discusses the possible mechanisms involved. Conclusion: Low penetrance genetic polymorphisms are promising candidates as biomarkers for colorectal cancer predisposition.
Cancer Genetics, 2017
This study aimed to investigate the association between FAS c.-671A&a... more This study aimed to investigate the association between FAS c.-671A>G polymorphism and cervical cancer risk in a case-control setting, followed by a meta-analysis of the published literatures. The case-control study involved genotyping of the polymorphism in 185 histopathologically confirmed cervical cancer patients and 209 cancer-free female controls utilizing PCR-RFLP technique, followed by logistic regression analyses. Meta-analysis was then conducted under homozygous, heterozygous, dominant, recessive and allele contrast models to combine data from 12 studies which consisted of 2798 cases and 3039 controls. Our case-control analysis revealed a significant association of the variant allele (G) and the homozygous variant genotype (GG) of the FAS polymorphism with an increased risk of cervical cancer. Subgroup analysis by ethnicity further confirmed the risk association in Malays (P < 0.05), but not among non-Malays (P > 0.05). However, results of meta-analysis suggested a lack of association between the polymorphism and cervical cancer risk in all the five genetic models analyzed. In conclusion, while the FAS c.-671A>G polymorphism may serve as a biomarker for cervical cancer risk prediction among the Malays, there is a limited usability of the polymorphism as a cervical cancer risk biomarker in other populations.
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, Jan 30, 2015
Dear Editor, I read with great interest two recent meta-analyses in Tumor Biology on the associat... more Dear Editor, I read with great interest two recent meta-analyses in Tumor Biology on the association of FAS c.-671A>G (rs1800682) polymorphism with cervical cancer risk [1, 2] (for clarification, FAS was known by its alternative symbol of CD95 in [1], and c.-671A>G polymorphism was referred to by its conventional designation of A670G in [2]). Both metaanalyses were performed using an exactly identical method and included the same set of ten individual studies from nine published reports. It is therefore not surprising that the two meta-analyses arrived at the same conclusion that there was a lack of significant association between the polymorphism and cervical cancer risk. It is interesting, however, to note that the odds ratios (ORs) obtained in the two meta-analyses were in opposite directions for all the four genetic models investigated. Upon close examination, I found several inaccuracies in the metaanalysis by Zhang et al. [1], which I would like to point out in this letter. Firstly, the authors appeared to have made a classification mistake when extracting data on genotype frequency from Chatterjee et al. [3]. The paper by Chatterjee et al. [3] contributed to two individual studies in the above meta-analysis. In the first study, Chatterjee et al. [3] reported that the ratio of subjects having AA, AG, and GG genotypes was 1:35:67 in cases and 2:43:54 in controls, but Zhang et al. [1] erroneously reversed the ratios to 67:35:1 and 54:43:2, respectively, in their meta-analysis. Similarly, in the second study by Chatterjee et al. [3], the correct genotypic ratios should be 53:132:147 and 39:146:136, instead of the 147:132:53 and 136:146:39 reported by Zhang et al. [1]. This mistake of genotypic classification probably arose because there has been no agreed consensus as to whether AA or GG genotype should be considered as the wild type among the ten individual studies included in the meta-analysis. While Zhang et al. [1] considered c.-671AA as the wild-type genotype and presented their data in the order of AA, AG, and GG, several individual studies (including that of Chatterjee et al. [3]) observed c.-671GG as the wild type and reported the genotypic frequencies in the opposite order of GG, GA, and AA. The varying orders in which the data was presented can sometimes lead to confusion, as in the present case. It is worth mentioning that the two individual studies by Chatterjee et al. [3] were given a combined weightage of >17 % in the meta-analysis, which was sufficiently substantial to alter the result of the meta-analysis when a classification mistake was committed. Besides, the main purpose of this meta-analysis was to evaluate the association of polymorphism with the risk of cervical cancer. As such, data on other cervical lesions, such as cervical intraepithelial neoplasia (CIN), should not have been included. In fact, Zhang et al. [1] themselves explicitly stated in their manuscript that data on CIN was excluded from the meta-analysis . Nevertheless, I found that the authors had still inadvertently incorporated data on CIN in their analysis. Specifically, the genotypic frequency reported in two of the studies included, namely those of Zoodsma * Shing Cheng Tan shingchengtan@gmail.com
Public Health Genomics
Objective: CDKN1A encodes for cyclin-dependent kinase inhib-itor 1A, which plays an important rol... more Objective: CDKN1A encodes for cyclin-dependent kinase inhib-itor 1A, which plays an important role in cell cycle regulation and apoptosis. The c.93C>A polymorphism of CDKN1A causes a serine-to-arginine substitution in the protein product, which could potentially influence its functionality. In this study, we investigated the association between CDKN1A c.93C>A polymorphism and cervical cancer risk. Material and Methods: The polymorphism was genotyped on 95 histopathologically confirmed cervical cancer patients and 95 cancer-free female controls by using PCR-RFLP technique. The risk association was evaluated by using logistic regression analysis. The finding was further stratified by self-reported ethnicity and human papillomavirus (HPV) type present in cervical smear of the subjects, as determined by using a flow-through hybridization method. Results: By using the wild type genotype as reference, we found no significant association between the polymorphism and cervical cancer risk (heterozygous OR = 0.821, 95% CI = 0.418–1.612, P = 0.57; homozygous variant OR = 0.936, 95% CI = 0.406–2.156, P = 0.88). A similar absence of significant association was observed when the results were stratified by the ethnicity of the study subjects (Malay, heterozygous P = 0.93, homozygous variant P = 0.78; Chinese, heterozygous P = 0.09, homozygous variant P = 0.31). Likewise, lack of association was observed when the results were stratified by HPV types (HPV-16, heterozygous P = 0.16, homozy-gous variant P = 0.08; HPV-18, heterozygous P = 0.13, homozygous variant P = 0.79; other minor HPV types, heterozygous P = 0.41, homozygous variant P = 0.29; HPV negative, heterozygous P = 0.91, homozygous variant P = 0.47; multiple HPV types, heterozygous P = 0.24, homozygous variant P = 0.31). Conclusion: In conclusion, the present study suggests a lack of association between CDKN1A c.93C>A polymorphism and cervical cancer risk.
Tumor Biology, 2015
Cervical cancer is a common malignancy which poses a significant health burden among women, espec... more Cervical cancer is a common malignancy which poses a significant health burden among women, especially those living in the developing countries. Although human papillomavirus (HPV) infection has been unequivocally implicated in the etiopathogenesis of the cancer, it alone is not adequate to contribute to the malignant transformation of cervical cells. Most HPV infections regress spontaneously, and only a small proportion of women have persistent infections which eventually lead to malignancy. This suggests that interplays between HPV infection and other cofactors certainly exist during the process of cervical carcinogenesis, which synergistically contribute to the differential susceptibility of an individual to the malignancy. Undoubtedly, host genetic factors represent a major element involved in such a synergistic interaction, and accumulating evidence suggests that polymorphisms in apoptosis-related genes play an important role in the genetic susceptibility to cervical cancer. This review consolidates the recent literatures on the role of common polymorphisms in apoptosis-related genes in genetic susceptibility to cervical cancer.
Aims: Apoptosis evasion is a hallmark of cancer. Fas receptor, encoded by FAS gene, is a transmem... more Aims: Apoptosis evasion is a hallmark of cancer. Fas receptor, encoded by FAS gene, is a transmembrane protein which plays a major function in mediating apoptosis. The –670A>G promoter polymorphism of FAS can alter the transcriptional activity of the gene. We aimed to investigate the association of FAS –670A>G polymorphism with human papillomavirus (HPV)-mediated cervical cancer risk among Malaysian subjects of Malay and Chinese ethnicities. Methods: The polymorphism was genotyped on 58 cervical cancer patients and 58 cancer-free female controls with PCR-RFLP technique. The association between the polymorphic genotypes and cervical cancer risk was assessed by using unconditional logistic regression analysis. Results: By using the wild type genotype as the reference, both the heterozygous (AG) and homozygous variant (GG) genotypes were found to increase cervical cancer risk (heterozygous OR=3.14, 95% CI=1.31-7.54, P=0.01; homozygous variant OR=6.14, 95% CI=1.89-19.93, P<0.01). When the results were stratified according to the ethnicity of the subjects, the association was present only among Malays (heterozygous OR=4.41, 95% CI=1.50-12.98, P=0.01; homozygous variant OR=6.71, 95% CI=1.46-30.73, P=0.01), but not among Chinese (P>0.05). Besides, stratification by HPV genotype of the patients revealed that significant risk modification effects exist only among cases with homozygous variant genotype who were infected by HPV-18 (OR=5.63, 95% CI=1.15-27.44, P=0.03) or simultaneously co-infected by more than one HPV genotype (OR=18.00, 95% CI=1.69-191.24, P=0.02). Conclusion: In conclusion, the variant allele of the FAS –670A>G polymorphism could increase cervical cancer risk in the population studied, especially among Malays and among patients with HPV-18 infection or co-infected by more than one HPV genotype.
Medical Oncology, 2013
The inhibitory protein IjBa, encoded by the NFKBIA gene, plays an important role in regulating th... more The inhibitory protein IjBa, 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 0 = 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.
Cancer Epidemiology, 2013
Information on the prevalence and type distribution of human papillomavirus (HPV) among Malaysian... more Information on the prevalence and type distribution of human papillomavirus (HPV) among Malaysian women is currently limited. The present study therefore aimed to provide an updated estimate on the prevalence and type distribution of HPV among Malaysian women with and without cervical cancer. Total DNA was isolated from the cervical cell specimens of 185 histopathologically confirmed cervical cancer patients and 209 cancer-free healthy females who were tested negative in a recent Pap test. Viral-specific DNA was subsequently amplified with biotinylated primers and hybridized to HPV type-specific probes via a proprietary "flow-through hybridization" process for determination of HPV genotype. It was demonstrated that 83.2% of the cervical cancer patients and none (0.0%) of the cancer-free females were positive for HPV infection. Among HPV-positive subjects, 14 different viral genotypes were observed, namely HPV16, 18, 31, 33, 35, 45, 52, 53, 58, 66/68, 73, 81, 82, and 84/26. A total of 91.6% of the HPV-positive subjects had single-type HPV infections and the remaining 8.4% were simultaneously infected by two HPV genotypes. The most common HPV infections found were HPV16 (35.7%), HPV18 (26.0%), HPV58 (9.1%), and HPV33 (7.1%) single-type infections, followed by HPV16 + HPV18 co-infections (5.2%). The study has successfully provided an updated estimate on the prevalence and type distribution of HPV among Malaysian women with and without cervical cancer. These findings could contribute valuable information for appraisal of the impact and cost-effectiveness of prophylactic HPV vaccines in the Malaysian population.
Introduction: Assessment of the prevalence and type distribution of human papillomavirus (HPV) is... more Introduction: Assessment of the prevalence and type distribution of human papillomavirus (HPV) is important for designing effective cervical cancer prevention programs. In this study, we evaluated the prevalence and type distribution of HPV among women with cervical cancer in Malaysia. Materials and Methods: Total DNA was isolated from the cervical smear specimens of 120 histopathologically-confirmed cervical cancer patients. Viral-specific DNA was amplified with biotinylated primers and hybridized to HPV type-specific probes via a flow-through process for determination of the presence and type of HPV. Result: Overall, HPV infection was detected in 106 specimens (88.3%). Among the HPV-positive samples, the most prevalent HPV types were HPV-16 (38.0%), HPV-18 (27.1%) and HPV-58 (6.2%). A similar distribution was observed in Malays when the data was stratified by ethnicity, with the prevalence of the three HPV types being 38.3%, 32.1% and 8.6%. In non-Malays, however, the three most prevalent HPV types were HPV-16 (47.1%), HPV-18 (26.5%) and HPV-81 (5.9%). Among the 53 specimens for which data on cancer histopathological subtype is available, the most prevalent HPV types in squamous cell carcinomas were HPV-16 (43.8%), HPV-18 (18.8%) and HPV-33 (12.5%). In adenocarcinoma, HPV-16 and HPV-18 remained the most prevalent HPV types (41.2% and 35.3% respectively), while HPV-31, HPV-45, HPV-58 and HPV-81 each made up 5.9% of the total infections. On the other hand, cervical carcinomas of other histopathological types contained HPV-18 exclusively (100.0%). Discussion: Slight difference exists on the distribution of HPV types in Malaysian cervical cancer cases of different ethnicity and histopathological subtypes.
Objective: CDKN1A encodes for cyclin-dependent kinase inhib-itor 1A, which plays an important rol... more Objective: CDKN1A encodes for cyclin-dependent kinase inhib-itor 1A, which plays an important role in cell cycle regulation and apoptosis. The c.93C>A polymorphism of CDKN1A causes a serine-to-arginine substitution in the protein product, which could potentially influence its functionality. In this study, we investigated the association between CDKN1A c.93C>A polymorphism and cervical cancer risk. Material and Methods: The polymorphism was genotyped on 95 histopathologically confirmed cervical cancer patients and 95 cancer-free female controls by using PCR-RFLP technique. The risk association was evaluated by using logistic regression analysis. The finding was further stratified by self-reported ethnicity and human papillomavirus (HPV) type present in cervical smear of the subjects, as determined by using a flow-through hybridization method. Results: By using the wild type genotype as reference, we found no significant association between the polymorphism and cervical cancer risk (heterozygous OR = 0.821, 95% CI = 0.418–1.612, P = 0.57; homozygous variant OR = 0.936, 95% CI = 0.406–2.156, P = 0.88). A similar absence of significant association was observed when the results were stratified by the ethnicity of the study subjects (Malay, heterozygous P = 0.93, homozygous variant P = 0.78; Chinese, heterozygous P = 0.09, homozygous variant P = 0.31). Likewise, lack of association was observed when the results were stratified by HPV types (HPV-16, heterozygous P = 0.16, homozy-gous variant P = 0.08; HPV-18, heterozygous P = 0.13, homozygous variant P = 0.79; other minor HPV types, heterozygous P = 0.41, homozygous variant P = 0.29; HPV negative, heterozygous P = 0.91, homozygous variant P = 0.47; multiple HPV types, heterozygous P = 0.24, homozygous variant P = 0.31). Conclusion: In conclusion, the present study suggests a lack of association between CDKN1A c.93C>A polymorphism and cervical cancer risk.
Aims: Apoptosis evasion is a hallmark of cancer. Fas receptor, encoded by FAS gene, is a transmem... more Aims: Apoptosis evasion is a hallmark of cancer. Fas receptor, encoded by FAS gene, is a transmembrane protein which plays a major function in mediating apoptosis. The –670A>G promoter polymorphism of FAS can alter the transcriptional activity of the gene. We aimed to investigate the association of FAS –670A>G polymorphism with human papillomavirus (HPV)-mediated cervical cancer risk among Malaysian subjects of Malay and Chinese ethnicities.
Methods: The polymorphism was genotyped on 58 cervical cancer patients and 58 cancer-free female controls with PCR-RFLP technique. The association between the polymorphic genotypes and cervical cancer risk was assessed by using unconditional logistic regression analysis.
Results: By using the wild type genotype as the reference, both the heterozygous (AG) and homozygous variant (GG) genotypes were found to increase cervical cancer risk (heterozygous OR=3.14, 95% CI=1.31-7.54, P=0.01; homozygous variant OR=6.14, 95% CI=1.89-19.93, P<0.01). When the results were stratified according to the ethnicity of the subjects, the association was present only among Malays (heterozygous OR=4.41, 95% CI=1.50-12.98, P=0.01; homozygous variant OR=6.71, 95% CI=1.46-30.73, P=0.01), but not among Chinese (P>0.05). Besides, stratification by HPV genotype of the patients revealed that significant risk modification effects exist only among cases with homozygous variant genotype who were infected by HPV-18 (OR=5.63, 95% CI=1.15-27.44, P=0.03) or simultaneously co-infected by more than one HPV genotype (OR=18.00, 95% CI=1.69-191.24, P=0.02).
Conclusion: In conclusion, the variant allele of the FAS –670A>G polymorphism could increase cervical cancer risk in the population studied, especially among Malays and among patients with HPV-18 infection or co-infected by more than one HPV genotype.
The inhibitory protein IκBα plays an important role in regulating the activity of nuclear factor-... more The inhibitory protein IκBα plays an important role in regulating the activity of nuclear factor-kappa B (NF-κB), a transcription factor which has been implicated in the initiation and progression of cancers. Genetic variations, such as single nucleotide polymorphisms in the NFKBIA gene which encodes for IκBα, could potentially lead to functional consequences of the protein product which could, in turn, modulate the risk of various cancers, including colorectal cancer (CRC). In this study, we investigated the frequencies of NFKBIA -826C>T (rs2233406) and -881A>G (rs3138053) polymorphic genotypes in Malaysian CRC patients and in cancer-free controls as well as evaluating the associations of the polymorphisms with CRC risk. A case-control study comprising of 237 CRC patients and an equal number of cancer-free controls was carried out. The polymorphisms were genotyped via PCR-RFLP, followed by DNA sequencing, from the genomic DNA of the study subjects. The association between the polymorphic genotypes and CRC risk was evaluated using unconditional logistic regression analysis. Our results showed that the two polymorphisms were in complete linkage disequilibrium (LD). The frequencies of the homozygous wild type, heterozygote and homozygous variant genotypes among the cases were 71.3%, 25.3% and 3.4% respectively, while those among the controls were 68.8%, 29.1% and 2.1%. The distribution of the polymorphic genotypes did not deviate significantly from the Hardy-Weinberg equilibrium (P cases = 0.36, P controls = 0.46). The heterozygote genotype was associated with a slightly reduced risk of CRC (OR = 0.84, 95% CI = 0.56 – 1.26), but without statistical significance (P = 0.40). Similarly, no statistically significant association was observed between the homozygous variant genotype and CRC risk (OR = 1.54, 95% CI = 0.50 – 4.82, P = 0.45). In conclusion, the present study suggests a lack of association between NFKBIA -826C>T and -881A>G polymorphisms and CRC risk.
European Journal of Cancer, 2015
Background: SOX2 is one of the pluripotency transcription factors expressed by stem cells, playin... more Background: SOX2 is one of the pluripotency transcription factors expressed by stem cells, playing a central role in maintenance of stemness and overexpressed in a variety of solid tumours. In breast cancer, SOX2 expression has mainly been reported in the basal-like subtype. We evaluated a heterogenous group of breast cancer tissues to determine whether the expression of SOX2 and other pluripotency transcription factors correlated with clinicopathological factors and recurrence.
Dear Editor, I read with great interest two recent meta-analyses in Tumor Biology on the associat... more Dear Editor, I read with great interest two recent meta-analyses in Tumor Biology on the association of FAS c.-671A>G (rs1800682) polymorphism with cervical cancer risk [1, 2] (for clarification, FAS was known by its alternative symbol of CD95 in [1], and c.-671A>G polymorphism was referred to by its conventional designation of A670G in [2]). Both metaanalyses were performed using an exactly identical method and included the same set of ten individual studies from nine published reports. It is therefore not surprising that the two meta-analyses arrived at the same conclusion that there was a lack of significant association between the polymorphism and cervical cancer risk. It is interesting, however, to note that the odds ratios (ORs) obtained in the two meta-analyses were in opposite directions for all the four genetic models investigated. Upon close examination,
Cervical cancer is a common malignancy which poses a significant health burden among women, espec... more Cervical cancer is a common malignancy which poses a significant health burden among women, especially those living in the developing countries. Although human papillomavirus (HPV) infection has been unequivocally implicated in the etiopathogenesis of the cancer, it alone is not adequate to contribute to the malignant transformation of cervical cells. Most HPV infections regress spontaneously, and only a small proportion of women have persistent infections which eventually lead to malignancy. This suggests that interplays between HPV infection and other cofactors certainly exist during the process of cervical carcinogenesis, which synergistically contribute to the differential susceptibility of an individual to the malignancy. Undoubtedly, host genetic factors represent a major element involved in such a synergistic interaction, and accumulating evidence suggests that polymorphisms in apoptosis-related genes play an important role in the genetic susceptibility to cervical cancer. This review consolidates the recent literatures on the role of common polymorphisms in apoptosis-related genes in genetic susceptibility to cervical cancer.
OBJECTIVE:
To investigate the allele and genotype frequencies of NFKB1 -94 ins/del ATTG (rs287202... more OBJECTIVE:
To investigate the allele and genotype frequencies of NFKB1 -94 ins/del ATTG (rs28720239) polymorphism and to evaluate the association between the polymorphism and colorectal cancer (CRC) risk in Malaysian population.
METHODS:
Genomic DNA was extracted from the peripheral blood samples of 474 study subjects, which consisted of 237 histopathologically confirmed CRC patients and an equal number of cancer-free controls. The NFKB1 -94 ins/del ATTG (rs28720239) polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and confirmed 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.
RESULTS:
The frequencies of wildtype (del/del), heterozygous (del/ins) and variant (ins/ins) genotypes in CRC patients were 31.7%, 53.6% and 14.8%, respectively, while those in cancer-free controls were 35.0%, 58.2% and 6.8%, respectively. The frequency of the variant genotype was significantly higher in cases compared to controls (P<0.01). Evaluation of the risk association of the polymorphic genotypes revealed that the variant genotype could contribute to a significantly increased risk of CRC (OR=2.42, 95% CI=1.24-4.73, P<0.01).
CONCLUSIONS:
The variant allele of NFKB1 -94 ins/del ATTG (rs28362491) polymorphism is associated with higher risk of sporadic CRC in Malaysian population
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Papers by Shing Cheng Tan
Methods: The polymorphism was genotyped on 58 cervical cancer patients and 58 cancer-free female controls with PCR-RFLP technique. The association between the polymorphic genotypes and cervical cancer risk was assessed by using unconditional logistic regression analysis.
Results: By using the wild type genotype as the reference, both the heterozygous (AG) and homozygous variant (GG) genotypes were found to increase cervical cancer risk (heterozygous OR=3.14, 95% CI=1.31-7.54, P=0.01; homozygous variant OR=6.14, 95% CI=1.89-19.93, P<0.01). When the results were stratified according to the ethnicity of the subjects, the association was present only among Malays (heterozygous OR=4.41, 95% CI=1.50-12.98, P=0.01; homozygous variant OR=6.71, 95% CI=1.46-30.73, P=0.01), but not among Chinese (P>0.05). Besides, stratification by HPV genotype of the patients revealed that significant risk modification effects exist only among cases with homozygous variant genotype who were infected by HPV-18 (OR=5.63, 95% CI=1.15-27.44, P=0.03) or simultaneously co-infected by more than one HPV genotype (OR=18.00, 95% CI=1.69-191.24, P=0.02).
Conclusion: In conclusion, the variant allele of the FAS –670A>G polymorphism could increase cervical cancer risk in the population studied, especially among Malays and among patients with HPV-18 infection or co-infected by more than one HPV genotype.
To investigate the allele and genotype frequencies of NFKB1 -94 ins/del ATTG (rs28720239) polymorphism and to evaluate the association between the polymorphism and colorectal cancer (CRC) risk in Malaysian population.
METHODS:
Genomic DNA was extracted from the peripheral blood samples of 474 study subjects, which consisted of 237 histopathologically confirmed CRC patients and an equal number of cancer-free controls. The NFKB1 -94 ins/del ATTG (rs28720239) polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and confirmed 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.
RESULTS:
The frequencies of wildtype (del/del), heterozygous (del/ins) and variant (ins/ins) genotypes in CRC patients were 31.7%, 53.6% and 14.8%, respectively, while those in cancer-free controls were 35.0%, 58.2% and 6.8%, respectively. The frequency of the variant genotype was significantly higher in cases compared to controls (P<0.01). Evaluation of the risk association of the polymorphic genotypes revealed that the variant genotype could contribute to a significantly increased risk of CRC (OR=2.42, 95% CI=1.24-4.73, P<0.01).
CONCLUSIONS:
The variant allele of NFKB1 -94 ins/del ATTG (rs28362491) polymorphism is associated with higher risk of sporadic CRC in Malaysian population
Methods: The polymorphism was genotyped on 58 cervical cancer patients and 58 cancer-free female controls with PCR-RFLP technique. The association between the polymorphic genotypes and cervical cancer risk was assessed by using unconditional logistic regression analysis.
Results: By using the wild type genotype as the reference, both the heterozygous (AG) and homozygous variant (GG) genotypes were found to increase cervical cancer risk (heterozygous OR=3.14, 95% CI=1.31-7.54, P=0.01; homozygous variant OR=6.14, 95% CI=1.89-19.93, P<0.01). When the results were stratified according to the ethnicity of the subjects, the association was present only among Malays (heterozygous OR=4.41, 95% CI=1.50-12.98, P=0.01; homozygous variant OR=6.71, 95% CI=1.46-30.73, P=0.01), but not among Chinese (P>0.05). Besides, stratification by HPV genotype of the patients revealed that significant risk modification effects exist only among cases with homozygous variant genotype who were infected by HPV-18 (OR=5.63, 95% CI=1.15-27.44, P=0.03) or simultaneously co-infected by more than one HPV genotype (OR=18.00, 95% CI=1.69-191.24, P=0.02).
Conclusion: In conclusion, the variant allele of the FAS –670A>G polymorphism could increase cervical cancer risk in the population studied, especially among Malays and among patients with HPV-18 infection or co-infected by more than one HPV genotype.
To investigate the allele and genotype frequencies of NFKB1 -94 ins/del ATTG (rs28720239) polymorphism and to evaluate the association between the polymorphism and colorectal cancer (CRC) risk in Malaysian population.
METHODS:
Genomic DNA was extracted from the peripheral blood samples of 474 study subjects, which consisted of 237 histopathologically confirmed CRC patients and an equal number of cancer-free controls. The NFKB1 -94 ins/del ATTG (rs28720239) polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and confirmed 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.
RESULTS:
The frequencies of wildtype (del/del), heterozygous (del/ins) and variant (ins/ins) genotypes in CRC patients were 31.7%, 53.6% and 14.8%, respectively, while those in cancer-free controls were 35.0%, 58.2% and 6.8%, respectively. The frequency of the variant genotype was significantly higher in cases compared to controls (P<0.01). Evaluation of the risk association of the polymorphic genotypes revealed that the variant genotype could contribute to a significantly increased risk of CRC (OR=2.42, 95% CI=1.24-4.73, P<0.01).
CONCLUSIONS:
The variant allele of NFKB1 -94 ins/del ATTG (rs28362491) polymorphism is associated with higher risk of sporadic CRC in Malaysian population