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Journal ArticleDOI

Meta-Analysis of Polymorphic Variants Conferring Genetic Risk to Cervical Cancer in Indian Women Supports CYP1A1 as an Important Associated Locus

01 Aug 2018-Asian Pacific Journal of Cancer Prevention (West Asia Organization for Cancer Prevention (WAOCP))-Vol. 19, Iss: 8, pp 2071-2081

TL;DR: This study revealed significant association of rs1048943 in CYP1A1, but a nominal association of deletion polymorphism (Del2) in GSTM1 with cervical cancer, which provides a comprehensive insight on the true effect of the polymorphisms, reported in various case-control studies, on the risk of the development of cervical cancer in Indian women.

AbstractObjective: Association of multiple polymorphic variants with cervical cancer has been elucidated by several candidate gene based as well as genome-wide association studies. However, contradictory outcomes of those studies have failed to estimate the true effect of the polymorphic variants on cervical cancer. Methods: Literature mining of the PubMed database was done to gather all the publications related to genetic association with cervical cancer in India. Out of 98 PubMed hits only 29 genetic association studies were selected for meta-analysis based on specific inclusion criteria. A fixed-effect meta-analysis was performed to evaluate the overall association of the genetic polymorphisms with cervical cancer. Cochran’s Q test was performed to assess between study heterogeneity. Publication bias was also estimated by funnel plots and Egger’s regression test. Further, sub-group analysis was conducted by fixed-effect meta-regression to assess the impact of polymorphisms on cervical cancer in the presence of Human Papilloma Virus (HPV). Result: Following a fixed-effect model, meta-analysis was conducted that revealed 2 polymorphic variants viz. ‘deletion polymorphism (Del2) (OR=1.79, 95% CI= 1.08-2.95, P=0.023) in GSTM1’ and ‘rs1048943 (OR = 2.34, 95% CI=1.37-3.99, P=0.0018) in CYP1A1’ to be associated with cervical cancer. However, multiple testing correction showed only rs1048943 of CYP1A1 to be significantly associated (P-value=0.029) with cervical cancer with significant publication bias (P-value=0.0113) as estimated by Egger’s regression test. The polymorphic variants ‘rs1801131’, ‘rs1801133’, ‘rs2430561’, ‘rs1799782’, ‘rs25486’ and ‘rs25487’ showed significant (p<0.05) evidence of heterogeneity between studies by Cochran’s Q test and also by heterogeneity index (I2) calculation. Conclusion: Therefore, our study revealed significant association of rs1048943 in CYP1A1, but a nominal association of deletion polymorphism (Del2) in GSTM1 with cervical cancer, which provides a comprehensive insight on the true effect of the polymorphisms, reported in various case-control studies, on the risk of the development of cervical cancer in Indian women.

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Citations
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Journal ArticleDOI
13 Jul 2019
TL;DR: The influence of certain factors inherent to the host, including the immune status, genetic variants and the coexistence of other microbe infections and microbiome composition in the dynamic of HPV infection induced carcinogenesis are highlighted.
Abstract: Every year nearly half a million new cases of cervix cancer are diagnosed worldwide, making this malignancy the fourth commonest cancer in women In 2018, more than 270,000 women died of cervix cancer globally with 85% of them being from developing countries The majority of these cancers are caused by the infection with carcinogenic strains of human papillomavirus (HPV), which is also causally implicated in the development of other malignancies, including cancer of the anus, penis cancer and head and neck cancer HPV is by far the most common sexually transmitted infection worldwide, however, most infected people do not develop cancer and do not even have a persistent infection The development of highly effective HPV vaccines against most common high-risk HPV strains is a great medical achievement of the 21st century that could prevent up to 90% of cervix cancers In this article, we review the current understanding of the balanced virus-host interaction that can lead to either virus elimination or the establishment of persistent infection and ultimately malignant transformation We also highlight the influence of certain factors inherent to the host, including the immune status, genetic variants and the coexistence of other microbe infections and microbiome composition in the dynamic of HPV infection induced carcinogenesis

23 citations

Journal ArticleDOI
TL;DR: It is reported that CDC25A is highly expressed and miR‐122‐5p lowly expressed in cervical cancer tissues and cells, and the data suggest that miR-122‐ 5p enhances the radiosensitivity of cervical cancer cells by targeting CDC25 a.
Abstract: Cervical cancer is one of the most common gynecological malignancies globally, Unfortunately, radiotherapy and chemotherapy are not effective at treating some cases of this disease, and the 5-year survival rate is only 40-50%. Cell division cycle 25A (CDC25A) has been shown to induce radioresistance in a variety of tumor cells, but the role of CDC25A in the radioresistance of cervical cancer has not been fully elucidated. Here, we report that CDC25A is highly expressed and miR-122-5p lowly expressed in cervical cancer tissues and cells. The TargetScan database was used to predict CDC25A as a target of miR-122-5p, and the interactions between miR-122-5p and CDC25A were further confirmed by western blot, real-time PCR and dual-luciferase reporter assay. Under X-ray irradiation, up-regulation of CDC25A can promote the radiation resistance of cervical cancer cells, whereas overexpression of miR-122-5p or knockdown of CDC25A inhibits the survival and induces apoptosis of cervical cancer colonies. In conclusion, our data suggest that miR-122-5p enhances the radiosensitivity of cervical cancer cells by targeting CDC25A.

17 citations

Journal ArticleDOI
27 Dec 2019-PLOS ONE
Abstract: Objective Endometriosis is a common chronic, gynecological disease. Despite many studies on the role of N-acetyltransferase 2 (NAT2) in endometriosis, its clinical significance is unclear. In this study, associations between NAT2 phenotypes as well as single nucleotide polymorphisms (SNPs) within NAT2 (i.e. rs1799929, rs1799930, rs1208, and rs1799931) and endometriosis risk were evaluated using a meta-analysis approach. Methods Embase, PubMed, ClinicalTrials.gov, CNKI (China National Knowledge Infrastructure), Wanfang databases, Cochrane Library for clinical trials, and Web of Science were searched to identify relevant articles. ORs (odds ratios) and 95% CIs (95% confidence intervals) were used to estimate the associations between NAT2 polymorphisms and endometriosis risk. Heterogeneity among included studies was also assessed. In addition, a subgroup analysis of NAT2 phenotypes and endometriosis risk based on ethnicity was performed. Results Nine case-control studies met the inclusion criteria. The odds ratio was 2.30 (95% CI: 1.61–3.28) for the NAT2 slow acetylation phenotype versus the intermediate + fast acetylation phenotype in the Asian population. These results suggest that Asian individuals with the NAT2 slow acetylation phenotype have a 130% increased risk of endometriosis. A significant association was also found for rs1799930 (OR = 0.74; 95% CI, 0.59–0.92), suggesting that individuals with this mutant genotype have a 26% decreased risk of endometriosis. Conclusions The rs1799930 mutant genotypes are associated with a decreased risk of endometriosis. No statistically significant associations were found between rs1799931, rs1208, or rs1799929 and endometriosis. Based on a subgroup analysis based on ethnicity, the NAT2 slow acetylation phenotype was found to increase the risk of endometriosis in Asians. No statistically significant associations were found between the NAT2 slow acetylation phenotype and endometriosis risk in Caucasians. Accordingly, NAT2 phenotypes and SNPs are potential biomarkers for the diagnosis and treatment of endometriosis.

6 citations


Cites background from "Meta-Analysis of Polymorphic Varian..."

  • ...Genes encoding many metabolic enzymes such as cytochrome P4501A1 (CYP1A1), catechol-O-methyltransferase (COMT), N-acetyltransferase 2 (NAT2), and glutathione S-transferase P1 (GSTP1) are associated with polymorphisms that can distinguish between populations....

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  • ...Abbreviations: 95% CI, 95% confidence interval; NAT2, N-acetyltransferase 2; CNKI, China National Knowledge Infrastructure; OR, odds ratio; CYP1A1, cytochrome P4501A1; CYP19A1, cytochrome P45019A1; COMT, catechol-O-methyl transferase; GSTP1, glutathione S-transferase P1; SNP, singlenucleotide polymorphism; NOS, Newcastle–Ottawa scale; BMI, body mass index; GWAS, genome-wide association studies; PCBs, polychlorinated biphenyls. hormones, and the immune system....

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  • ...Other xenobiotic metabolic enzymes like aromatase P450 family members CYP1A1 and CYP19A1 [24] also have a fundamental role in the pathogenesis of endometriosis [23, 25], and have been widely studied and applied to endometriosis treatment....

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  • ...Recent meta-analysis-based studies have investigated the relationships between polymorphisms in GSTP1 [6], COMT [7], and CYP1A1 [8] and the risk of endometriosis....

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Journal ArticleDOI
TL;DR: This is the first study of its kind from the Indian subcontinent analysing the extent of association of variants across populations followed by their functional annotation in the disease pathway and finds the del2/GSTM1 holds the association in premenopausal women.
Abstract: Background: Genetic association studies on breast cancer on the Indian subcontinent have yielded conflicting results, and the precise effect of these variants on breast cancer pathogenesis is not known. Methods: Genomic variants, as obtained from selected studies from the Indian subcontinent, were subjected to random-effects and fixed-effect meta-analysis. Functional annotation of the relevant variants was done through a tried and tested in silico pipeline. Results: We found rs4646903/CYP1A1, rs1799814/CYP1A1, rs61886492/GCPII, del2/GSTM1, rs4680/COMT and rs1801394/MTRR to be associated with breast cancer. The del2/GSTM1 holds the association in premenopausal women. Conclusions: This is the first study of its kind from the Indian subcontinent analysing the extent of association of variants across populations followed by their functional annotation in the disease pathway.

4 citations

Journal ArticleDOI
Abstract: Introduction Nasopharyngeal carcinoma (NPC) is a common cancer in southern China and Taiwan, and radiation therapy combined with or without chemotherapy is its mainstay treatment. Although it is highly sensitive to radiotherapy, local recurrence and distant metastasis remain difficult unsolved problems. In recent years, graphene oxide (GO) has been found to be a promising novel anticancer drug carrier. Here, we present our designed functionalized GO, polyethylene glycol-coated GO (GO-PEG), as a drug carrier, which was loaded with erlotinib and showed promising anticancer effects on NPC cells. Methods The effects of GO-PEG-erlotinib on the proliferation, migration, and invasion of NPC cells were investigated by WST-8 assay, wound healing assay, and invasion assay, respectively. RNA sequencing was conducted and analyzed to determine the molecular mechanisms by which GO-PEG-erlotinib affects NPC cells. Results Our results showed that GO-PEG-erlotinib reduced NPC cell viability in a dose-dependent manner and also inhibited the migration and invasion of NPC cells. The RNA sequencing revealed several related molecular mechanisms. Conclusion GO-PEG-erlotinib effectively suppressed NPC cell proliferation, migration, and invasion, likely by several mechanisms. GO-PEG-erlotinib may be a potential therapeutic agent for treating NPC in the future.

4 citations


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"Meta-Analysis of Polymorphic Varian..." refers methods in this paper

  • ...2 (R Core Team, 2017) package ‘metafor’ (Viechtbauer, 2010) considering fixed-effect model (Borenstein et al....

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  • ...Meta-analysis was performed in R, 3.4.2 (R Core Team, 2017) package ‘metafor’ (Viechtbauer, 2010) considering fixed-effect model (Borenstein et al., 2010), on genetic association reports pertaining to Indian population (Sengupta et al., 2017) ignoring ethnicity and geographical distribution…...

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Abstract: Copyright (©) 1999–2009 R Foundation for Statistical Computing. Permission is granted to make and distribute verbatim copies of this manual provided the copyright notice and this permission notice are preserved on all copies. Permission is granted to copy and distribute modified versions of this manual under the conditions for verbatim copying, provided that the entire resulting derived work is distributed under the terms of a permission notice identical to this one. Permission is granted to copy and distribute translations of this manual into another language, under the above conditions for modified versions, except that this permission notice may be stated in a translation approved by the R Development Core Team.

6,942 citations


"Meta-Analysis of Polymorphic Varian..." refers methods in this paper

  • ...Meta-analysis was performed in R, 3.4.2 (R Core Team, 2017) package ‘metafor’ (Viechtbauer, 2010) considering fixed-effect model (Borenstein et al., 2010), on genetic association reports pertaining to Indian population (Sengupta et al., 2017) ignoring ethnicity and geographical distribution…...

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Journal ArticleDOI
TL;DR: It is the right time for medical societies and public health regulators to consider the causal role of human papillomavirus infections in cervical cancer and to define its preventive and clinical implications.
Abstract: The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. The association is present in virtually all cervical cancer cases worldwide. It is the right time for medical societies and public health regulators to consider this evidence and to define its preventive and clinical implications. A comprehensive review of key studies and results is presented.

3,161 citations


"Meta-Analysis of Polymorphic Varian..." refers background in this paper

  • ...Persistent HPV infection along with other risk modifiers synergistically act to cause cellular transformations that leads to cervical cancer (Bosch et al., 2002; Hakama and Day, 1986; Moscicki et al., 2012)....

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Journal ArticleDOI
TL;DR: This paper explains the key assumptions of each model, and outlines the differences between the models, to conclude with a discussion of factors to consider when choosing between the two models.
Abstract: There are two popular statistical models for meta-analysis, the fixed-effect model and the random-effects model. The fact that these two models employ similar sets of formulas to compute statistics, and sometimes yield similar estimates for the various parameters, may lead people to believe that the models are interchangeable. In fact, though, the models represent fundamentally different assumptions about the data. The selection of the appropriate model is important to ensure that the various statistics are estimated correctly. Additionally, and more fundamentally, the model serves to place the analysis in context. It provides a framework for the goals of the analysis as well as for the interpretation of the statistics. In this paper we explain the key assumptions of each model, and then outline the differences between the models. We conclude with a discussion of factors to consider when choosing between the two models. Copyright © 2010 John Wiley & Sons, Ltd.

2,669 citations


"Meta-Analysis of Polymorphic Varian..." refers background or methods in this paper

  • ...Meta-analysis was performed in R, 3.4.2 (R Core Team, 2017) package ‘metafor’ (Viechtbauer, 2010) considering fixed-effect model (Borenstein et al., 2010), on genetic association reports pertaining to Indian population (Sengupta et al., 2017) ignoring ethnicity and geographical distribution…...

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  • ...Sub-group meta-analysis of rs1042522 of TP53 was done following the fixed-effect model (Borenstein et al., 2010)....

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  • ...2 (R Core Team, 2017) package ‘metafor’ (Viechtbauer, 2010) considering fixed-effect model (Borenstein et al., 2010), on genetic association reports pertaining to Indian population (Sengupta et al....

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