Role of available COVID-19 vaccines in reducing deaths and perspective for next generation vaccines and therapies to counter emerging viral variants: an update.

The COVID-19 disease wreaked havoc all over the world causing more than 6 million deaths out of over 519 million confirmed cases. It not only disturbed the human race health-wise but also caused huge economic losses and social disturbances. The utmost urgency to counter pandemic was to develop effective vaccines as well as treatments that could reduce the incidences of infection, hospitalization and deaths. The most known vaccines that could help in managing these parameters are Oxford-AstraZeneca (AZD1222), Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273) and Johnson & Johnson (Ad26.COV2.S). The effectiveness of AZD1222 vaccine in reducing deaths is 88% in the age group 40-59 years, touching 100% in the age group 16-44 years & 65-84 years. BNT162b2 vaccine also did well in reducing deaths due to COVID-19 (95% in the age group 40-49 years and 100% in the age group 16-44 years. Similarly, mRNA-1273 vaccine showed potential in reducing COVID-19 deaths with effectiveness ranging from 80.3 to 100% depending upon age group of the vaccinated individuals. Ad26.COV2.S vaccine was also 100% effective in reducing COVID-19 deaths. The SARS-CoV-2 emerging variants have emphasized the need of booster vaccine doses to enhance protective immunity in vaccinated individuals. Additionally, therapeutic effectiveness of Molnupiravir, Paxlovid and Evusheld are also providing resistance against the spread of COVID-19 disease as well as may be effective against emerging variants. This review highlights the progress in developing COVID-19 vaccines, their protective efficacies, advances being made to design more efficacious vaccines, and presents an overview on advancements in developing potent drugs and monoclonal antibodies for countering COVID-19 and emerging variants of SARS-CoV-2 including the most recently emerged and highly mutated Omicron variant.

Differential differentiation of B cell lymphopoiesis in lethal and non-lethal murine malaria models.

B cells in protection against malaria and need of experiencing many episodes in humans to achieve a state of immunity is largely unknown. The cellular basis of such defects in terms of B cell generation, maturation and trafficking was studied by taking Plasmodium chabaudi, a non-lethal and Plasmodium berghei, a lethal murine model. A flow cytometry (FCF) based evaluation was used to study alterations in generation and maintenance of B cells in patients with Plasmodium falciparum malaria as well as in murine malaria models. A significant accumulation of mature B cells in bone marrow and immature B cells in circulation was a feature observed only in lethal malaria. At peak parasitaemia, both the models induce a significant decrease in T2 (transitional) B cells with expansion of T1B cells. Studies in patients with acute Pf malaria showed a significant expansion of memory B cells and TB cells with a concomitant decrease in naive2 B cells as compared with healthy controls. This study clearly demonstrates that acute malarial infection induces major disturbances in B cell development in lymphoid organs and trafficking in periphery.

Cytotoxic T-lymphocyte associated protein 4 (CTLA4) polymorphisms are linked to systemic lupus erythematosus: an updated meta-analysis.

Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) molecule controls T cell immune response. Functional single nucleotide polymorphisms (SNPs) in the CTLA-4 gene have been associated with several autoimmune diseases, including systemic lupus erythematosus (SLE).  However, the genetic association of the CTLA-4 variants with vulnerability to SLE remained contradictory. We have conducted a current meta-analysis by combining the findings of prior published articles in order to make a conclusive statement. Various literature databases were screened with appropriate keywords to obtain relevant articles, and eligible reports were obtained using well-defined inclusion and exclusion criteria. Meta-analysis was performed by Comprehensive Meta-analysis V 3.3, and various statistical parameters such as odds ratio, 95% confidence interval, and probability values were computed. A total of 3847 SLE patients and 5278 healthy controls were considered in the present meta-analysis from 26 individual reports. A significant association of CTLA-4 +49 A/G (G vs. A: p=0.03, OR=1.47) and -1722 T/C (p=0.02, OR=0.87) polymorphisms were observed with susceptibility and resistance against the development of SLE, respectively. However, the other two SNPs in the CTLA-4 gene (-318 C/T and -1661 A/G) failed to establish a connection. Interestingly, subgroup analysis revealed an association of CTLA-4 +49 A/G with a predisposition to SLE only in the Asian population (G vs. A: p=0.04, OR=1.26, GG vs. AA: p=0.02, OR=1.84, AG vs AA: p=0.01, OR=1.44, GG+AG vs AA: p=0.01, OR=1.52) and not in Caucasians. The current meta-analysis suggests a significant CTLA-4 +49 A/G variant association with susceptibility to SLE development in overall and Asian populations. In contrast, the other variant, -1722 T/C, is linked with protection against SLE. However, further case-control studies in diverse ethnic populations are requisite.

Combined effect of ipilimumab and nivolumab improves oncology endpoints in metastatic melanoma patients.

Metastatic melanoma has less frequency, but considered as the most dreaded cancer. The combination of nivolumab & ipilimumab is proving their mettle in treating metastatic melanoma. The patients when administered with the combination of nivolumab & ipilimumab have shown improved median progression free survival, objective response rate and overall survival rate compared with nivolumab and ipilimumab monotherapy. The combination shrinks the tumor cells by attacking different checkpoints viz. CTLA-4 and PD-L1, respectively. The combination treatment reveals reduced disease progression and suggests nivolumab's non-cross resistant nature. The median progression free survival in "nivolumab plus ipilimumab" group has shown an increase of 66.7% and 296.6% in comparison to nivolumab and ipilimumab monotherapy. The other parameter viz. objective response rate improvement is equivalent to almost 14% and 38.6% when compared to nivolumab and ipilimumab monotherapy, respectively.

Diet as a modifiable factor in tumorigenesis: Focus on microbiome-derived bile acid metabolites and short-chain fatty acids.

Several lines of evidences have implicated the resident microbiome as a key factor in the modulation of host physiology and pathophysiology; including the resistance to cancers. Gut microbiome heavily influences host lipid homeostasis by their modulatory effects on the metabolism of bile acids (BAs). Microbiota-derived BA metabolites such as deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) are implicated in the pathogeneses of various cancer types. The pathogenic mechanisms are multimodal in nature, with widespread influences on the host immunes system, cell survival and growth signalling and DNA damage. On the other hand, short-chain fatty acids (SCFAs) produced by the resident microbial activity on indigestible dietary fibres as well as during intermittent fasting regimens (such as the Ramazan fasting) elicit upregulation of the beneficial anti-inflammatory and anticancer pathways in the host. The present review first provides a brief overview of the molecular mechanisms of microbiota-derived lipid metabolites in promotion of tumour development. The authors then discuss the potential of diet as a therapeutic route for beneficial alteration of microbiota and the consequent changes in the production of SCFAs, particularly butyrate, in relation to the cancer prevention and treatment.

Prioritization and characterization of validated biofilm blockers targeting glucosyltransferase C of Streptococcus mutans.

To date, several Glucosyltransferase C (GtfC) inhibitors have been identified and experimentally validated. All these inhibitors have been validated at different experimental conditions like degree of purity, animal models, kinetic conditions, experimental environment etc.; and most of these inhibitors (ligands) proved to be quite effective in their respective validation environment. However, due to varied experimental validation conditions, and absence of molecular interaction data, there is no way to prioritize these validated ligands for their inhibition potential against GtfC. The present study is a novel attempt of comparative evaluation of the interaction of the validated ligands on a single platform and under similar conditions with a dual objective, i.e. ligand prioritization for their respective inhibitory potential and elucidation of the involved unknown molecular interactions. Carbohydrate derivatives (6-Deoxy sucrose and Trichloro-galactosucrose) were identified as the most promising GtfC inhibitors. In addition, Asp588, Trp517, and Asn481 amino acid residues of the domain A1 proved vital for the inhibitory effect. The study highlights the importance of the comparative analysis of the validated ligands in order to identify the most promising leads for drug discovery against dental caries.

IFN-γ +874 A>T (rs2430561) gene polymorphism and risk of pulmonary tuberculosis: a meta-analysis.

INTRODUCTION: The role of interferon gamma (IFN-γ) +874 A>T (rs2430561) gene polymorphism has been evaluated in different ethnicities with pulmonary tuberculosis (PTB) infection, and inconsistent results have been reported. In this study, a meta-analysis was performed to determine the precise association between IFN-γ +874 A>T gene polymorphism and PTB susceptibility. MATERIAL AND METHODS: A total of 21 studies comprising 4281 confirmed PTB cases and 5186 healthy controls were included in this meta-analysis by searching the PubMed (Medline), EMBASE, and Google Scholar web-databases. RESULTS: We observed reduced risk of PTB in allelic contrast (T vs. A: p = 0.001; OR = 0.818, 95% CI: 0.723-0.926), homozygous (TT vs. AA: p = 0.017; OR = 0.715, 95% CI: 0.543-0.941), heterozygous (AT vs. AA: p = 0.002; OR = 0.782, 95% CI: 0.667-0.917), dominant (TT+AT vs. AA: p = 0.002; OR = 0.768, 95% CI: 0.652-0.906), and recessive (TT vs. AA+AT: p = 0.042; OR = 0.802, 95% CI: 0.649-0.992) genetic models. In ethnicity-wise subgroup analysis, reduced risk of PTB was found in the Caucasian population. However, we did not find an association with any of the genetic models in the Asian population. CONCLUSIONS: In conclusion, the IFN-γ +874 A>T gene polymorphism is significantly associated with reduced risk of PTB, showing a protective effect in the overall and in the Caucasian population. However, this polymorphism is not associated with PTB risk in the Asian population.

Potency of inhibitors depends upon the accessibility of their aromatic rings within the hydrophobic specificity pocket: a novel avenue for future aldose reductase inhibitor design.

Communicated by Ramaswamy H. Sarma.

Glutathione S-Transferase P1 313 (A > G) Ile105Val Polymorphism Contributes to Cancer Susceptibility in Indian Population: A Meta-analysis of 39 Case-Control Studies.

GSTP1 involved in the metabolism of carcinogens and toxins, reduces damage of DNA and act as a suppressor of carcinogenesis. Many studies have reported that 313 A > G polymorphism is associated with different cancer in Indian population, but the results remain conflicting rather than conclusive. Therefore, we have performed meta-analysis to clarify the more precise association of GSPT1 313 A > G polymorphism with cancer risk in Indian population. We retrieved all relevant published literature from PubMed (Medline) and Google scholar web database and included those study only based on the established inclusion criteria. Pooled ORs and 95% CIs were used to appraise the strength of association. Publication bias and sensitivity analysis was also evaluated. A total of 6581 confirmed cancer cases and 8218 controls were included from eligible thirty nine case-controls studies. Pooled analysis suggested that the variant genotypes significantly increased the risk of cancer in allele (G vs. A: OR 1.266, 95% CI 1.129-1.418, p = 0.001), heterozygous (AG vs. AA: OR 1.191, 95% CI 1.047-1.355, p = 0.008), homozygous (GG vs. AA: OR 1.811, 95% CI 1.428-2.297, p = 0.001), dominant (GG + AG vs. AA: OR 1.276, 95% CI 1.110-1.466, p = 0.001) and recessive (GG vs. AG + AA: OR 1.638, 95% CI 1.340-2.002, p = 0.001) genetic models. The stability of these observations was confirmed by a sensitivity analysis. Begger's funnel plot and Egger's test did not reveal any publication bias. This meta-analysis suggests that the GSTP1 313 A > G polymorphism may contribute to genetic susceptibility to cancer in Indian population. However, larger studies and randomized clinical trial will be required to elucidate the biological and molecular mechanism of GSTP1 gene in cancer.

Link between MnSOD Ala16Val (rs4880) polymorphism and asthma risk is insignificant from sequential meta-analysis.

The mitochondrial manganese superoxide dismutase (MnSOD) enzyme protects lungs against oxidative stress by neutralizing the free radical superoxide produced in the respiratory function. This has relevance to asthma. Therefore, it is of interest to describe the potential effect of MnSOD Ala16Val genetic polymorphism to asthma risk. Known data in this context is inconclusive in nature. The possible link between MnSOD Ala16Val polymorphism and asthma is explored using sequence meta-analysis. Data from the pooled analysis of MnSOD Ala16Val polymorphism using five genetic models i.e., allelic (Val vs. Ala: p=0.846; OR=1.033, 95% CI=0.742 to 1.440) is discussed. Homozygous (Val Val vs. Ala Ala: p=0.517; OR=1.307, 95% CI=0.582 to 2.932) and heterozygous (Val Ala vs. Ala Ala: p=0.307; OR=1.138, 95% CI=0.888 to 1.459) data using the described models are documented. Data from the dominant model (Val Val + Val Ala vs. Ala Ala: p=0.301; OR=1.289, 95% CI=0.797 to 2.085) and the recessive model (Val Val vs. Val Ala + Ala Ala: p=0.761; OR=0.924, 95% CI=0.555 to 1.538) analyses for several ethnic subgroups in this context is reported.

Genistein Modulates Signaling Pathways and Targets Several Epigenetic Markers in HeLa Cells.

BACKGROUND: Several epigenetic changes are responsible for transcriptional alterations of signaling pathways and tumour suppressor genes (TSGs) contributing to carcinogenesis. This study was aimed to examine the effect of the phytochemical, genistein on various molecular targets in HeLa cells. METHODS: Quantitative PCR was used to analyze the expression of various molecular targets. Biochemical assays were employed to study the epigenetic enzymes. To correlate the transcriptional status of the selected TSGs and epigenetic modulation, their promoter 5'CpG methylation levels were evaluated by quantitative methylation array followed by methylation specific restriction digestion. RESULTS: The expression of several genes involved in the cell cycle regulation, migration, inflammation, phosphatidylinositol 3-kinase (PI3K) and mitogen activated kinase-like protein (MAPK) pathway were found to be modulated including CCNB1, TWIST1, MMP14, TERT, AKT1, PTPRR, FOS and IL1A. Genistein modulated the expression of DNA methyltransferases (DNMTs), histone deacetylases (HDACs), histone methyltransferases (HMTs), demethylases, and histone phosphorylases. Furthermore, genistein decreased the activity of DNMTs, HDACs, and HMTs and reduced global DNA methylation levels. Promoter methylation of several TSGs, including FHIT, RUNX3, CDH1, PTEN, and SOC51, was lowered with corresponding transcriptional increase. Network analysis indicated similar effect of genistein. CONCLUSION: This study presents a comprehensive mechanism of action of genistein showcasing effective epigenetic modulation and widespread transcriptional changes resulting in restoration of tumour suppressor gene expression. This study corroborates the development of genistein as a candidate for anti-cancer therapy.

AA genotype of cyclin D1 G870A polymorphism increases breast cancer risk: Findings of a case-control study and meta-analysis.

BACKGROUND: Cyclin D1 (CCND1) polymorphisms, a regulator of the cell cycle progress from G1 to the S phase, may lead to uncontrolled cell proliferation and lack of apoptosis. G870A, a common single-nucleotide polymorphism in CCND1 influences breast cancer risk. However, the association between G870A polymorphism and breast cancer risk is ambiguous so far. MATERIALS AND METHODS: In this case-control study, we analyzed the role of G870A polymorphism with breast cancer risk in Indian women. A meta-analysis of 18 studies was also performed to elucidate this association by increasing statistical power. RESULTS: In our case-control study, significant risk association of the CCND1 G870A AA genotype with breast cancer in total cohort (odds ratio [OR], 2.98; 95% confidence interval [CI], 1.64-5.42; P value, 4.96e-04) and premenopausal women (OR, 3.31; 95% CI, 1.54-7.08; P value, .003) was found. The results of the meta-analysis showed that AA genotype of the CCND1 G870A polymorphism significantly increases breast cancer risk in total pooled data (AA vs GG+GA: OR = 1.20; 95% CI = 1.03 to 1.39; P value, 0.016*) and Caucasian (AA vs GG+GA: OR = 1.22; 95% CI = 0.99 to 1.51; P value, .056*) but not in Asian population. Further, a significant protective association with breast cancer was also found in the GA vs AA comparison model in pooled data (OR = 0.73; 95% CI = 0.58 to 0.92; P value, .007*) as well as in Caucasian subgroup (OR = 0.62; 95% CI = 0.49 to 0.94; P value, .022*). CONCLUSION: CCND1 G870A AA genotype was found associated with breast cancer risk. Future association studies considering the environmental impact on gene expression are required to validate/explore this association.

A trial sequential meta-analysis of IFN-γ +874 A>T (rs2430561) gene polymorphism and extrapulmonary tuberculosis risk.

Interferon-γ (IFN-γ) plays a crucial role in immunological responses against Mycobacterium tuberculosis (M.tb) infection. The polymorphism at +874 A > T (rs2430561) influences the levels of IFN-γ, which may further influence the susceptibility to extrapulmonary tuberculosis (EPTB). This polymorphism has been investigated with respect to EPTB occurrence in different populations and provided contradictory and conflicting results. This study was performed to meta-statistically analyze the data and draw a more accurate conclusion regarding the association of IFN-γ +874 A > T gene polymorphism and EPTB susceptibility. A quantitative synthesis was executed for the pertinent studies retrieved from online web-databases viz. Google Scholar, PubMed/Medline and EMBASE. The pooled odds ratios (ORs) and confidence intervals (95% CIs) were estimated for all the genetic models by meta-analysis. A total of eight studies were retrieved which included 762 confirmed EPTB cases and 1341 controls. The meta-analysis results revealed reduced association of EPTB in allelic contrast (T vs. A: p = 0.001; OR = 0.668, 95% CI = 0.524 to 0.850), homozygous (TT vs. AA: p = 0.017; OR = 0.450, 95% CI = 0.234 to 0.868), heterozygous (AT vs. AA: p = 0.004; OR = 0.574, 95% CI = 0.395 to 0.835), dominant (TT + AT vs. AA: p = 0.003; OR = 0.536, 95% CI = 0.354 to 0.810) and recessive (TT vs. AA + AT: p = 0.039; OR = 0.662, 95% CI = 0.448 to 0.980) genetic models. Furthermore, re-sampling statistics also revealed reduced risk of EPTB in overall population and Asian subgroup. This meta-analysis concluded that IFN-γ +874 A > T gene polymorphism is meaningfully related with the reduced EPTB risk in overall and Asian population, and further necessitates larger studies to be conducted on this topic in other races.

Association of MBL2 gene polymorphisms with pulmonary tuberculosis susceptibility: trial sequence meta-analysis as evidence.

BACKGROUND: Mannose-binding lectin (MBL) or mannose-binding protein (MBP), encoded by MBL2 gene and secreted by the liver, activates complement system through lectin pathway in innate immunity against the host's infection. Conflictingly, a number of MBL2 variants, rs1800450 (A>B), rs1800451 (A>C), rs5030737 (A>D), rs7096206 (Y>X), rs11003125 (H>L), and rs7095891 (P>Q) allele, have been found to be associated with compromised serum levels and pulmonary tuberculosis (PTB) susceptibility. The present meta-analysis study was performed to evaluate the potential association of these MBL2 gene variants with PTB susceptibility. MATERIALS AND METHODS: A quantitative synthesis was performed on PubMed (Medline), EMBASE, and Google Scholar web database searches. A meta-analysis was performed to calculate the pooled odds ratios and 95% CIs for all the genetic models. RESULTS: A total of 14 eligible studies were included to analyze their pooled data for associations between alleles, genotypes, and minor allele carriers. The statistical analysis revealed the significant reduced PTB risk with homozygous variant genotype of rs1800451 polymorphism (CC vs AA: P=0.043; OR =0.828, 95% CI =0.689-0.994). Contrary to this, the variant allele of rs5030737 polymorphism showed association with increased PTB risk (D vs A: P=0.026; OR =1.563, 95% CI =1.054-2.317). However, the other genetic models of rs1800450 (A>B), rs7096206 (Y>X), and rs11003125 (H>L) MBL2 gene polymorphisms did not divulge any association with PTB susceptibility. CONCLUSION: The current meta-analysis concludes that rs1800451 (A>C) and rs5030737 (A>D) polymorphisms of MBL2 gene play a significant role in PTB susceptibility. Further, well-designed epidemiological studies with larger sample size including consideration of environmental factors are warranted for the future.

Niacin deficiency modulates genes involved in cancer: Are smokers at higher risk?

The role of niacin's metabolite, nicotinamide adenine dinucleotide (NAD), in DNA repair via base-excision repair pathway is well documented. We evaluated if niacin deficiency results in genetic instability in normal human fetal lung fibroblasts (MRC-5), and further, does it leads to enhanced accumulation of cigarette smoke-induced genetic damage? MRC-5 cells were grown discretely in niacin-proficient/deficient media, and exposed to nicotine-derived nitrosamine ketone (NNK, a cigarette smoke carcinogen). Niacin deficiency abated the NAD polymerization, augmented the spontaneous induction of micronuclei (MN) and chromosomal aberrations (CA) and raised the expression of 10 genes and suppressed 12 genes involved in different biological functions. NNK exposure resulted in genetic damage as measured by the induction of MN and CA in cells grown in niacin-proficient medium, but the damage became practically marked when niacin-deficient cells were exposed to NNK. NNK exposure raised the expression of 16 genes and suppressed the expression of 56 genes in cells grown in niacin-proficient medium. NNK exposure to niacin-deficient cells raised the expression of eight genes including genes crucial in promoting cancer such as FGFR3 and DUSP1 and suppressed the expression of 33 genes, including genes crucial in preventing the onset and progression of cancer like RASSF2, JUP, and IL24, in comparison with the cells grown in niacin-proficient medium. Overall, niacin deficiency interferes with the DNA damage repair process induced by chemical carcinogens like NNK, and niacin-deficient population are at the higher risk of genetic instability caused by cigarette smoke carcinogen NNK.

Pharmacogenetic association between NAT2 gene polymorphisms and isoniazid induced hepatotoxicity: trial sequence meta-analysis as evidence.

Hepatotoxicity is a severe problem generally faced by tuberculosis (TB) patients. It is a well-known adverse reaction due to anti-TB drugs in TB patients undergoing long-term treatment. The studies published previously have explored the connection of N-acetyltransferase 2 (NAT2) gene polymorphisms with isoniazid-induced hepatotoxicity, but the results obtained were inconsistent and inconclusive. A comprehensive trial sequence meta-analysis was conducted employing 12 studies comprising 3613 controls and 933 confirmed TB cases using the databases namely, EMBASE, PubMed (Medline) and Google Scholar till December 2017. A significant association was observed with individuals carrying variant allele at position 481C>T (T vs. C: P = 0.001; OR = 1.278, 95% CI = 1.1100-1.484), at position 590G>A (A vs. G: P = 0.002; OR = 1.421, 95% CI = 1.137-1.776) and at position 857G>A (A vs. G: P = 0.0022; OR = 1.411, 95% CI = 1.052-1.894) to higher risk of hepatotoxicity vis-à-vis wild-type allele. Likewise, the other genetic models of NAT2 gene polymorphisms have also shown increased risk of hepatotoxicity. No evidence of publication bias was observed. These results suggest that genetic variants of NAT2 gene have significant role in isoniazid induced hepatotoxicity. Thus, NAT2 genotyping has the potential to improve the understanding of the drug-enzyme metabolic capacity and help in early predisposition of isoniazid-induced hepatotoxicity.

A trial sequential meta-analysis of TNF-α -308G>A (rs800629) gene polymorphism and susceptibility to colorectal cancer.

PURPOSE: Tumor necrosis factor-α (TNF-α), secreted by the activated macrophages, may participate in the onset and progression of colorectal cancer (CRC). The association of TNF-α -308 G>A (rs1800629) single-nucleotide polymorphism (SNP) with CRC risk has been investigated by many studies but the results are inconclusive. A trial sequential meta-analysis was performed for precise estimation of the relationship between TNF-α -308 G>A gene polymorphism with CRC risk. METHODS: Medline (PubMed), EMBASE (Excerpta-Medica) and Google Scholar were mined for relevant articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the significance of association. RESULTS: The pooled analysis indicated no risk associated with TNF-α -308 G>A SNP and overall CRC risk in five genetic comparison models, i.e. allelic (A vs. G: P = 0.524; OR = 1.074, 95% CI = 0.863-1.335), homozygous (AA vs. GG: P = 0.489; OR = 1.227, 95% CI = 0.688-2.188), heterozygous (AG vs. GG: P = 0.811; OR = 1.024, 95% CI = 0.843-1.244), dominant (AA+AG vs. GG: P = 0.630; OR = 1.055, 95% CI = 0.849-1.311) and recessive (AA vs. AG+GG: P = 0.549; OR = 1.181, 95% CI = 0.686-2.033). Subgroup analysis revealed that TNF-α -308 G>A SNP is associated with reduced risk of CRC in Asian ethnicity. The study showed no publication bias. CONCLUSIONS: No association of TNF-α -308 G>A SNP with overall CRC risk was found. This SNP is likely to be protective against CRC in Asian population when compared with Caucasian population. Larger prospective-epidemiological studies are warranted to elucidate the roles of TNF-α -308 G>A SNP in the etiology of CRC and to endorse the present findings.

Genetic Variant Arg399Gln G>A of XRCC1 DNA Repair Gene Enhanced Cancer Risk Among Indian Population: Evidence from Meta-analysis and Trial Sequence Analyses.

The X-ray repair cross-complementation group 1 (XRCC1) gene plays an important role in base excision repair pathway. Several studies have reported contradictory results for XRCC1 exon 10 (Arg399Gln, G23990A, rs25487) gene polymorphism and cancer risk in Indian population, making it difficult to interpret them. Therefore, we have conducted a meta-analysis to evaluate the more precise association between XRCC1 exon 10 G>A gene polymorphism and risk of cancer by published studies. We searched PubMed (Medline) and Google scholar web databases to cover all studies published on association between XRCC1 exon 10 G>A gene polymorphism and cancer risk until August 2016. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to appraise the strength of association. Heterogeneity, publication bias and sensitivity analysis were also assessed. Twenty-five published studies had fulfilled the inclusion criteria comprising 4131 confirmed cancer cases and 5013 controls. When all studies were polled together, overall significant association was found between XRCC1 exon 10 G>A polymorphism and cancer risk in variant allele carrier (A vs. G: OR 1.217, 95% CI 1.056-1.402, p = 0.007), homozygous (AA vs. GG: OR 1.359, 95% CI 1.036-1.783, p = 0.027), dominant (AA+AG vs. GG OR 1.208, 95% CI 1.006-1.450, p = 0.043) and recessive (AA vs. AG+GG: OR 1.315, 95% CI 1.029-1.680, p = 0.029) genetic models. Further sensitivity analysis supported the stability of our result by showing similar ORs before and after removal of a single study. The present meta-analysis suggested that the XRCC1 exon 10 G>A polymorphism contribute cancer risk in Indian population, and supports that individuals with risk allele A and AA genotype are at higher risk of developing cancer.

Impact of p53 arg72pro SNP on Breast Cancer Risk in North Indian Population.

BACKGROUND: Genetic changes in p53 gene contribute to breast cancer susceptibility. OBJECTIVE AND METHODS: A case-control study and a meta-analysis were performed to investigate the role of p53 codon72 SNP with breast cancer susceptibility in Indian women. RESULTS: p53 heterozygous arginine variant was associated with decreased risk of breast cancer in total cohort. In meta-analysis, Allelic and GG vs. CC genetic comparison model were found to be associated with breast cancer risk. Moreover, recessive comparison model indicated a protective correlation with breast cancer occurrence. CONCLUSION: The findings of our case-control study and meta-analysis suggest a significant association between p53 Arg72Pro polymorphism and an increased risk of breast cancer in Indian population.

Meta-analysis reveals no correlation of caveolin-1 G14713A (G>A) gene polymorphism with increased cancer risk in Taiwanese population.

OBJECTIVES: The role of caveolin-1 (CAV1)(G>A, rs3807987) polymorphism is still dubious in cancer causation in Taiwanese population. The present study is an effort to assess the above relation for precise conclusion. METHODS: EMBASE and PubMed (MEDLINE) databases were explored for the pertinent case-control studies reporting the connection of CAV1 G14713A polymorphism to the vulnerability to cancer. A cumulative analysis using meta-analytic approach was accomplished and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for all the polymorphs. RESULTS: Overall, 2549 subjects and 3161 controls were analyzed from six selected studies. Our study showed no confirmation of noteworthy risk between CAV1 G14713A polymorphism and susceptibility to cancer in any of the polymorph, for instance, allele (A vs. G: P = 0.165; OR = 1.252, 95% CI = 0.911-1.721), homozygous (AA vs. GG: P = 0.252; OR = 1.328, 95% CI = 0.817-2.157), heterozygous (AG vs. GG: P = 0.091; OR = 1.356, 95% CI = 0.952-1.930), dominant (AA vs. GG + AG: P = 0.345; OR = 1.191, 95% CI = 0.829-1.709), and recessive (AA + AG vs. GG: P = 0.125; OR = 1.344, 95% CI = 0.921-1.961). CONCLUSIONS: We conclude that CAV1 G14713A polymorphism does not contribute as an independent predisposing risk factor for developing cancer in Taiwanese population.