Lysyl oxidase G473A (rs1800449) polymorphism influences the risk of cancer progression: a meta-analysis

Abstract The genetics of cancer progression is important for the design of optimal therapeutic strategies. Lysyl oxidase (LOX) is a cancer progression gene that has been studied enough to warrant a synthesis of its primary data from association studies. However, reported associations between the LOX G473A (rs1800449) gene polymorphism and cancer have been inconsistent, prompting a meta-analysis so that we could obtain more precise estimates. Database searches of the published literature yielded seven case-control studies. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) using four genetic models: homozygous (H), recessive (R), dominant (D) and codominant (C). Subgroup analysis was based on ethnicity and cancer type. Outlier analysis was used to examine sources of heterogeneity. The strength of evidence was based on the magnitude of effects, high associative significance, consistency and homogeneity. H/R outcomes exerted more associative effects than D/C results. Two reasons for this are as follows: (i) H/R analyses precluded outlier treatment; and (ii) the magnitude of H/R (ORs of > 2.0) was twice that of D/C (ORs > 1.0). All else being equal, significant pooled ORs in all genetic models had high significance (Pa < 10-5). Strong evidence for associations was found in the outcomes for Asian and gastrointestinal (GI) cancers. In summary, the LOX rs1800449 polymorphism confers significant overall susceptibility, particularly in GI cancers, and places Asians at risk.

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Lysyl oxidase 473G/A (rs1800449) polymorphism influences the risk of cancer progression: a meta-analysis

10.21203/rs.2.18129/v1 ◽

2019 ◽

Author(s):

Rungrawee Mongkolrob ◽

Phuntila Tharabenjasin ◽

Aporn Bualuang ◽

Noel Pabalan

Keyword(s):

Cancer Progression ◽

Bayes Factor ◽

Lysyl Oxidase ◽

Association Studies ◽

Meta Analysis ◽

Genetic Models ◽

Primary Data ◽

Cancer Type ◽

Digestive Cancers ◽

Risk Of Cancer

Abstract The genetics of cancer progression is important for devising optimal therapeutic strategies. Lysyl oxidase (LOX) is a cancer progression gene that has been studied enough to warrant synthesis of its primary data from association studies. However, reported associations between the LOX G473A (rs1800449) gene polymorphisms and cancer have been inconsistent prompting a meta-analysis so that we could obtain more precise estimates. Databases searches of the published literature yielded seven case-control studies. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) using four genetic models, homozygous (H), recessive (R), dominant (D) and codominant (C). Subgroup analysis was based on ethnicity and cancer type. Outlier analysis was used to examine sources of heterogeneity. Strength of evidence was based on high associative significance (expressed in terms of the Bayes Factor), consistency and magnitude of effects, homogeneity and robustness. H/R outcomes exerted more associative effects than D/C results. Two reasons for these are: (i) H/R analyses precluded outlier treatment; (ii) magnitude of H/R (ORs of > 2.0) was twice that of D/C (ORs > 1.0). All else being equal, significant pooled ORs in all genetic models had high significance (Pa < 10-5). Strong evidence for associations were found in the outcomes for Asian and digestive cancers. In summary, the LOX rs1800449 polymorphism confers significant overall susceptibility, particularly in digestive cancers and places Asians at risk.

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The association of FOXP3 gene polymorphisms with cancer susceptibility: a comprehensive systemic review and meta-analysis

Bioscience Reports ◽

10.1042/bsr20181809 ◽

2019 ◽

Vol 39 (3) ◽

Author(s):

Yan Chen ◽

Xiaoxue Qi ◽

Ce Bian ◽

Chen Ling ◽

Tao Yi ◽

...

Keyword(s):

Gene Polymorphisms ◽

Chinese Population ◽

Cancer Susceptibility ◽

Meta Analysis ◽

Systemic Review ◽

Cancer Type ◽

Case Control Studies ◽

Foxp3 Gene ◽

Cancer Types ◽

Risk Of Cancer

Abstract The role of forkhead box P3 (FOXP3) protein in tumorigenesis has long been controversial and existing data on the association between FOXP3 gene polymorphisms and cancer susceptibility were inconsistent. Here, we conducted a meta-analysis to better clarify the relationship. A comprehensive search of studies published from July 2008 to June 2018 was conducted. The statistical analyses of the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs) were performed using the Revman 5.2 software. A total of 12 articles with 19 case–control studies and 10389 participants were included. Three FOXP3 polymorphisms and six cancer types were evaluated. While no significant results were observed in overall and breast cancer groups for rs3761548 (A/C) polymorphisms, the pooled data showed an elevated risk of cancer in variant AA genotypes and A allele for Chinese population (AA vs. AC+CC: OR = 1.61, 95% CI = 1.09, 2.39; AA vs. CC: OR = 1.74, 95% CI = 1.05, 2.89; A vs. C: OR = 1.34, 95% CI = 1.00, 1.78). Neither the overall group analyses nor the subgroup analyses stratified by cancer type and ethnicity proposed any significant association of rs2280883 (C/T) and rs3761549 (T/C) polymorphisms with cancer susceptibility. This meta-analysis suggested that FOXP3 rs3761548 (A/C) polymorphisms were associated with increased cancer risk in Chinese population while rs2280883 (C/T) and rs3761549 (T/C) polymorphisms were not. More large-sample researches with diverse ethnicities and cancer types are needed to draw a concrete conclusion.

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Toll-like receptor 9 and 4 gene polymorphisms in susceptibility and severity of malaria: a meta-analysis of genetic association studies

Malaria Journal ◽

10.1186/s12936-021-03836-6 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Cho Naing ◽

Siew Tung Wong ◽

Htar Htar Aung

Keyword(s):

Association Studies ◽

Meta Analysis ◽

Public Health Problem ◽

Genetic Models ◽

Geographical Region ◽

Sub Saharan Africa ◽

Major Public Health Problem ◽

Asian Countries ◽

Case Control Studies ◽

Allele Model

Abstract Background Malaria is still a major public health problem in sub-Saharan Africa and South-east Asia. The clinical presentations of malaria infection vary from a mild febrile illness to life-threatening severe malaria. Toll like receptors (TLRs) are postulated to be involved in the innate immune responses to malaria. Individual studies showed inconclusive findings. This study aimed to assess the role of TLR4 (D299G, T399I) and TLR9 (T1237C, T1486C) in severity or susceptibility of malaria by meta-analysis of data from eligible studies. Methods Relevant case–control studies that assessed the association between TLR 4/9 and malaria either in susceptibility or progression were searched in health-related electronic databases. Quality of included studies was evaluated with Newcastle–Ottawa scale. Pooled analyses for specific genetic polymorphisms were done under five genetic models. Stratified analysis was done by age and geographical region (Asian countries vs non-Asian countries). Results Eleven studies (2716 cases and 2376 controls) from nine endemic countries were identified. Five studies (45.4%) obtained high score in quality assessment. Overall, a significant association between TLR9 (T1486C) and severity of malaria is observed in allele model (OR: 1.26, 95% CI: 1.08–1.48, I2 = 0%) or homozygous model (OR: 1.55, 95% CI: 1.08–2.28, I2 = 0%). For TLR9 (T1237C), a significant association with severity of malaria is observed in in heterozygous model (OR:1.89, 95% CI: 1.11–3.22, I2 = 75%). On stratifications, TLR9 (T1486C) is only significantly associated with a subgroup of children of non-Asian countries under allele model (OR: 1.25, 95% CI: 1.02–1.38), while 1237 is with a subgroup of adults from Asian countries under heterozygous model (OR: 2.0, 95% CI: 1.09–3.64, I2 = 39%). Regarding the susceptibility to malaria, TLR9 (T1237C) is significantly associated only with the children group under recessive model (OR: 2.21, 95% CI: 1.06–4.57, I2=85%) and homozygous model (OR: 1.49, 95% CI: 1.09–2.0, I2 = 0%). For TLR4 (D299G, T399I), none is significantly associated with either severity of malaria or susceptibility to malaria under any genetic models. Conclusions The findings suggest that TLR 9 (T1486C and T1237C) seems to influence the progression of malaria, under certain genetic models and in specific age group of people from specific geographical region. TLR 9 (T1237C) also plays a role in susceptibility to malaria under certain genetic models and only with children of non-Asian countries. To substantiate these, future well designed studies with larger samples across endemic countries are needed.

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Relation between Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms and Migraine Susceptibility

10.1101/19011601 ◽

2019 ◽

Author(s):

Vandana Rai ◽

Pradeep Kumar

Keyword(s):

Methylenetetrahydrofolate Reductase ◽

Association Studies ◽

Meta Analysis ◽

Asian Population ◽

Mthfr C677t ◽

Mthfr Gene ◽

Genetic Models ◽

C677t Polymorphism ◽

Case Control Studies ◽

Mthfr C677t Polymorphism

AbstractMigraine is a neurological disorder which impairs the patient’s quality of life. Several association studies investigating the association between MTHFR gene C677T and A1298C polymorphisms and susceptibility to migraine were published. But the results were conflicting, so authors performed a meta-analysis of published case control studies. Four databases were searched for suitable studies up to December, 2018. Odds ratios (OR) with 95% confidence intervals (CI) was calculated adopting additive, homozygote, co-dominant, dominant, and recessive genetic models.Results of MTHFR C677T polymorphism studies meta-analysis showed significant association with migraine risk using allele contrast, homozygote, dominant and recessive genetic models (T vs. C: OR = 1.18, 95%CI = 1.00-1.26, p= 0.05; TT vs. CC: OR = 1.24, 95%CI = 1.0-1.5, p= 0.04; CT vs. CC: OR = 1.08, 95%CI = 0.97-1.07, p= 0.25; TT+CT vs. CC: OR = 1.15, 95%CI = 1.0-1.29, p= 0.04; TT vs. CT +CC: OR = 1.97, 95%CI = 1.28-3.42, p= 0.002). However, results of MTHFR A1298 polymorphism studies meta-analysis did not show any association with migraine. Subgroup analysis based on ethnicity and migraine types i. e migraine with aura (MA) and without aura (MO) were also performed. Results of present meta-analysis indicate overall association between MTHFR C677T polymorphism with migraine in total 24 studies, in Asian population and in MA cases but did not show any association with Caucasian population and MO cases.

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Heat Shock Protein 70 Gene Polymorphisms and Cancer Risk: A Meta-Analysis

The Scientific World JOURNAL ◽

10.1155/2014/540309 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Lei He ◽

Tao Deng ◽

He-sheng Luo

Keyword(s):

Heat Shock ◽

Cancer Risk ◽

Heat Shock Protein ◽

Heat Shock Protein 70 ◽

Meta Analysis ◽

Recessive Model ◽

Cancer Type ◽

Case Control Studies ◽

Knowledge Infrastructure ◽

Risk Of Cancer

The polymorphisms in the three main heat shock protein 70 (HSP70-1, HSP70-2, and HSP70-hom) genes were identified to be associated with cancer risk. However, the results are inconsistent. We perform a meta-analysis to evaluate the association between the three HSP70 polymorphisms and cancer risk. Relevant studies were identified using PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases up to March 29, 2014. The cancer risk associated with the HSP70 polymorphisms was estimated for each study by odds ratios (OR) together with its 95% confidence interval (CI), respectively. Twenty case-control studies from eighteen publications were included; a significant association was observed for HSP70-2 polymorphism (dominant model: OR = 1.53, 95% CI: 1.11–2.09; recessive model: OR = 1.91, 95% CI: 1.06–3.45; AG versus AA: OR = 1.38, 95% CI: 1.03–1.84; GG versus AA: OR = 2.34, 95% CI: 1.21–4.54), while there was no significant association for HSP70-1 and HSP70-hom polymorphisms. Besides, in stratification analyses by ethnicity, cancer type, and source of control, significant association was detected for HSP70-2 polymorphism, while for HSP70-hom polymorphism, we found a significant association in hospital-based population under homozygote comparison model. This meta-analysis suggests that the HSP70-2 polymorphism rather than HSP70-hom and HSP70-1 polymorphisms was associated with the risk of cancer.

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Analyzing 37,900 Samples Shows Significant Association between Hotair Polymorphisms and Cancer Susceptibility: A Meta-Analysis

The International Journal of Biological Markers ◽

10.5301/jbm.5000235 ◽

2017 ◽

Vol 32 (2) ◽

pp. 231-242 ◽

Cited By ~ 6

Author(s):

Yating Ge ◽

Runze Jiang ◽

Meng Zhang ◽

Hao Wang ◽

Li Zhang ◽

...

Keyword(s):

Cancer Susceptibility ◽

Meta Analysis ◽

Protective Role ◽

Case Control ◽

Genetic Models ◽

Cancer Type ◽

Case Control Studies ◽

Heterogeneous Model ◽

The Relationship ◽

Increased Susceptibility

Background and objective An increasing number of investigations are drawing attention to the relationship between polymorphisms in the HOTAIR gene and the risk of cancers, but the results obtained so far have been controversial and inconclusive. We performed an up-to-date meta-analysis to obtain a more precise estimate of the possible associations. Methods Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. Results Nine publications including 26 case-control studies comprising 37,900 individuals were enrolled for the 5 polymorphisms in HOTAIR. The overall analyses identified a significant association between the rs920778 polymorphism and increased susceptibility to cancer in homozygous and recessive models. We conducted a stratification analysis by cancer type and identified a significantly increased susceptibility to esophageal squamous cell carcinoma in all the genetic models and to gastric cancer in the dominant model. For the rs7958904 polymorphism we detected a significantly decreased susceptibility to overall cancer in all 5 genetic models rather than the heterogeneous model. However, no significant association was identified between the rs874945, rs4759314 and rs1899663 polymorphisms and cancer susceptibility. Conclusions Our results demonstrate that the HOTAIR rs920778 polymorphism may represent a risk factor for cancer, whereas the rs7958904 polymorphism may play a protective role.

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The Association between PON1 (Q192R and L55M) Gene Polymorphisms and Risk of Cancer: A Meta-Analysis Based on 43 Studies

BioMed Research International ◽

10.1155/2019/5897505 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Xiaolan Pan ◽

Lei Huang ◽

Meiqin Li ◽

Dan Mo ◽

Yihua Liang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Risk ◽

Gene Polymorphisms ◽

Meta Analysis ◽

Population Based ◽

Case Control ◽

Cancer Type ◽

Case Control Studies ◽

Increased Risk ◽

Risk Of Cancer

Q192R and L55M polymorphism were considered to be associated with the development of multiple cancers. Nevertheless, the results of these researches were inconclusive and controversial. Therefore, we conducted a meta-analysis of all eligible case-control studies to assess the association between PON1 (Q192R and L55M) gene polymorphisms and risk of cancer. With the STATA 14.0 software, we evaluated the strength of the association by using the odds ratios (ORs) and 95% confidence intervals (CIs). A total of 43 case-control publications 19887 cases and 23842 controls were employed in our study. In all genetic models, a significant association between PON1-L55M polymorphisms and overall cancer risk was observed. Moreover, in the stratified analyses by cancer type, polymorphism of PON1-L55M played a risk factor in the occurrence of breast cancer, hematologic cancer, and prostate cancer. Similarly, an increased risk was observed in the Caucasian and Asian population as well as hospital-based group and population-based group. For PON1-Q192R polymorphisms, in the stratified analyses by cancer type, PON1-Q192R allele was associated with reduced cancer risks in breast cancer. Furthermore, for racial stratification, there was a reduced risk of cancer in recession model in Caucasian population. Similarly, in the stratification analysis of control source, the overall risk of cancer was reduced in the heterozygote comparison and dominant model in the population-based group. In conclusion, PON1-Q192R allele decreased the cancer risk especially breast cancer; there was an association between PON1-L55M allele and increased overall cancer risk. However, we need a larger sample size, well-designed in future and at protein levels to confirm these findings.

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Association between ACE A240T polymorphism and cancer risk: a meta-analysis

Journal of International Medical Research ◽

10.1177/0300060519882559 ◽

2019 ◽

Vol 47 (12) ◽

pp. 5917-5925 ◽

Cited By ~ 3

Author(s):

Yingjun Xiao ◽

Zheqing Dong ◽

Ji Zhu ◽

Jinbiao You ◽

Jun Fan

Keyword(s):

Cancer Risk ◽

Subgroup Analysis ◽

Large Scale ◽

Meta Analysis ◽

Convincing Evidence ◽

Cancer Type ◽

Case Control Studies ◽

Ace Gene ◽

Risk Of Cancer ◽

The Relationship

Objectives The relationship between the A240T polymorphism in the angiotensin-converting enzyme ( ACE) gene and cancer risk remains controversial. Therefore, we conducted a meta-analysis of relevant studies from the published literature. Methods We comprehensively searched available databases to identify eligible studies on the relationship of ACE A240T polymorphism with cancer risk. We calculated pooled odds ratios (OR) with 95% confidence intervals (CI) and then evaluated heterogeneity and publication bias. Results Eight case-control studies were identified from five articles. Results showed that the ACE A240T polymorphism was related to cancer risk (AT vs AA: OR 2.14, 95% CI: 1.51–3.04; TT vs AA: OR 1.07, 95% CI: 0.90–1.27; recessive model: OR 0.48, 95% CI: 0.31–0.77; dominant model: OR 2.13, 95% CI: 1.54–2.97). The same conclusion was made for subgroup analysis by race or cancer type. In the subgroup analysis by quality score assessment, the ACE A240T polymorphism contributed to cancer risk in high-quality studies but not in low-quality studies. Conclusion The A240T polymorphism in the ACE gene might be related to the risk of cancer. Nevertheless, large-scale studies should be performed to obtain convincing evidence on the roles of ACE A240T polymorphism on cancer risk.

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-196 to -174del, rs4696480, rs3804099 polymorphisms of Toll-like receptor 2 gene impact the susceptibility of cancers: evidence from 37053 subjects

Bioscience Reports ◽

10.1042/bsr20191698 ◽

2019 ◽

Vol 39 (12) ◽

Cited By ~ 1

Author(s):

Sheng-Lin Gao ◽

Yi-Ding Chen ◽

Chuang Yue ◽

Jiasheng Chen ◽

Li-Feng Zhang ◽

...

Keyword(s):

Cancer Risk ◽

Direct Evidence ◽

Meta Analysis ◽

Genetic Models ◽

Toll Like Receptor ◽

Case Control Studies ◽

Cancer Risks ◽

Toll Like Receptor 2 ◽

Risk Of Cancer ◽

The Relationship

Abstract Relationship between Toll-like receptor-2 (TLR2) and cancer risk has been illustrated in some studies, but their conclusions are inconsistent. Therefore, we designed this meta-analysis to explore a more accurate conclusion of whether TLR2 affects cancer risks. Articles were retrieved from various literature databases according to the criteria. We used STATA to calculate the odds ratio (OR) and 95% confidence interval (95% CI) to evaluate the relationship between certain polymorphism of TLR2 and cancer risk. Finally, 47 case–control studies met the criteria, comprising 15851 cases and 21182 controls. In the overall analysis, people are more likely to get cancer because of -196 to -174del in TLR2 in all five genetic models, B vs. A (OR = 1.468, 95% Cl = 1.129–1.91, P=0.005); BB vs. AA (OR = 1.716, 95% Cl = 1.178–2.5, P=0.005); BA vs. AA (OR = 1.408, 95% Cl = 1.092–1.816, P=0.008); BB+BA vs. AA (OR = 1.449, 95% Cl = 1.107–1.897, P=0.007); BB vs. BA+AA (OR = 1.517, 95% Cl = 1.092–2.107, P=0.013). Meanwhile, rs4696480 could significantly increase the risk of cancer in Caucasians, furthermore, rs3804099 significantly decreased cancer risk in overall analysis, but more subjects are necessary to confirm the results. All in all, this meta-analysis revealed that not only -196 to -174del increased the risk of among overall cancers, Caucasians are more likely to get cancer because of rs4696480, while rs3804099 polymorphism could reduce the risk of cancer in some genetic models. There is no direct evidence showing that rs5743708, rs3804100 and rs1898830 are related to cancer.

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Lysyl Oxidase Mechanisms to Mediate Gastrointestinal Cancer Progression

Gastrointestinal Tumors ◽

10.1159/000511244 ◽

2020 ◽

pp. 1-10

Author(s):

Ahmadshah Farhat ◽

Gordon A. Ferns ◽

Korosh Ashrafi ◽

Mohammad-Hassan Arjmand

Keyword(s):

Cancer Progression ◽

Extracellular Enzymes ◽

Lysyl Oxidase ◽

Ecm Remodeling ◽

Complex Process ◽

High Prevalence ◽

Different Types ◽

Fibrotic Diseases ◽

Gi Cancers ◽

Improvement In Survival

Background: Malignancy is a complex process resulting from different changes such as extracellular matrix (ECM) remodeling and stiffness. One of the important enzymes that contribute to ECM remodeling is lysyl oxidase (Lox) that is overexpressed in different types of human cancers. Because of the high prevalence and poor survival of gastrointestinal (GI) malignancies in this review, we discuss the association between Lox activity and the progression of GI cancers. Lox proteins are a group of extracellular enzymes that catalyzed the cross-linking of collagen and elastin, so they have important roles in the control of structure and homeostasis of ECM. Abnormal activation and expression of the Lox family of proteins lead to changes in the ECM toward increased rigidity and fibrosis. Stiffness of ECM can contribute to the pathogenesis of cancers. Summary: Dysregulation of Lox expression is a factor in both fibrotic diseases and cancer. ECM stiffness by Lox overactivity creates a physical barrier against intratumoral concentration of chemotherapeutic drugs and facilitates cancer inflammation, angiogenesis, and metastasis. Key Message: Because of the roles of Lox in GI cancers, development targeting Lox protein isotypes may be an appropriate strategy for treatment of GI cancers and improvement in survival of patients.

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