Global health economics: The Equitable Impact Sensitive Tool (EQUIST) - development, validation, implementation and evaluation of impact (2011 to 2022).

Background: The Equitable Impact Sensitive Tool (EQUIST) was developed to address the limitations of the traditional cost-effectiveness analysis (CEA) in global health, which often overlooked equity considerations. Its primary aim was to create more effective and efficient health systems by explicitly incorporating equity as a key driver in health policy decisions. This was done in response to the recognition that, while CEA helped reduce mortality rates through interventions like childhood vaccinations, it was insufficient in addressing growing inequalities in health, especially in low-and-middle-income countries (LMICs). Methods: The development of EQUIST involved a multi-stage process which began in 2011 with the recognition of the need for a more nuanced approach than CEA alone. This led to a proposal for creating a tool that balanced cost-effectiveness with equity. The conceptual framework, developed between March and May 2012, included assessments of intervention efficiency by equity strata, effectiveness, impact, and cost-effectiveness. Key to EQUIST's development was its integration with other data science platforms, notably the Lives Saved Tool and the Marginal Budgeting for Bottlenecks tool, allowing EQUIST to draw on comprehensive data sets and thus enabling a more detailed analysis of health interventions' impacts across different socio-economic strata. Results: EQUIST was validated in 2012 through applications in five representative countries, demonstrating its ability to identify more equitable and cost-effective health interventions which targeted vulnerable populations, leading to more lives saved compared to traditional methods. It was then used to develop investment cases for the Global Financing Facility, resulting in significant funding being made available for maternal and child health programmes. Consequently, EQUIST directly influenced the development of national health policies and resource allocations in over 26 African countries. Conclusions: EQUIST has proven to be a valuable tool in developing health policies that are both cost-effective and equitable. In the future, it will be further integrated with other tools and expanded in scope to address broader health issues, including adolescent health and human immunodeficiency virus/acquired immunodeficiency syndrome programme planning. Overall, EQUIST represents a paradigm shift in global health economics, emphasising the importance of equity alongside cost-effectiveness in health policy decisions. Its development and implementation have had a tangible impact on health outcomes, particularly in LMICs, where it has been instrumental in reducing maternal and child mortality while addressing health inequities.

Efficacy of Chitosan Scaffolded Calcium Silicate-based Cements for Treating Internal Resorption Defects with Perforation: In Vitro Study.

AIM: The present study aimed to evaluate the efficacy of chitosan scaffold combined with calcium silicate cements in the management of internal resorption with perforation. MATERIALS AND METHODS: Internal resorption cavities were simulated in 20 human permanent maxillary incisors that were then divided into two groups: group I - biodentine and group II - chitosan scaffold combined with biodentine. The samples were evaluated for the mineralization activity at the end of the 7th day and 14th day using scanning electron microscopy-energy dispersive X-ray (SEM-EDX) analysis. The data were recorded, tabulated, and then statistically analyzed. RESULTS: From the SEM-EDX analysis, the mean score of calcium and phosphorus ion uptake by the material was obtained. Statistical analysis by nonparametric Mann-Whitney test showed that there was statistically significant difference in calcium ion uptake at the end of the 7th day (p = 0.016) and at the end of 14th day (p = 0.043) between the group biodentine and group chitosan scaffold combined with biodentine (p < 0.05). CONCLUSION: In this present study, the use of chitosan scaffolds combined with biodentine showed a statistically significant difference in the mineralization activity when compared with pure biodentine. These scaffolded biomaterials exhibited greater potential for mineralization in vitro which can be efficiently used for the management of teeth with internal resorption with perforation. Further clinical trials are required for the understanding of their behavior in real-world scenarios. CLINICAL SIGNIFICANCE: Calcium silicate cements have often exhibited defective hard tissue barrier formation and hence there is a pressing need to search for newer biomaterials that can overcome these shortcomings. Scaffolded biomaterials provide a controlled microcellular environment for bioactivity, and they were found to be efficient in the remineralization of tooth structure. The present study findings indicate that these chitosan scaffolds can be efficiently used in combination with calcium silicate cements for the management of internal resorption with perforation to enhance the treatment outcome.

Cyclic Fatigue Resistance of Different Glide Path Files in Simulated Double Curved Canal in Continuous Rotary Motion: An In Vitro Study.

AIM: This in vitro study aimed to compare and evaluate the resistance to cyclic fatigue of a newly developed glide path file in a simulated double curvature canal in a cyclic fatigue-testing machine. METHODS: In this in vitro study, a static cyclic fatigue-testing machine with a simulated double curve was created and the samples were divided into the following three groups: Group I-HyFlex EDM; group II-TruNatomy file; and group III-Aurum G files and each instrument is continued to rotate in the canal and a number of cycles to failure (NCF) was calculated and Fractographic analysis was done using scanning electron microscope (SEM), and the results were statistically analyzed. RESULTS: Statistical analysis was done using parametric methods one-way analysis of variance (ANOVA) shows statistical significance between groups and then Tukey's HSD post hoc tests were used for multiple pairwise comparisons. TruNatomy glide path files had the highest cyclic fatigue resistance when compared to HyFlex EDM and Aurum G files. CONCLUSION: The selection of file systems in cleaning and shaping protocols is an enigma to endodontics. From the results of this study, it can be concluded that TruNatomy files had higher cyclic fatigue resistance than other glide path files are canals with double curvature, hence it is suitable for usage in root canals with extreme curvature. CLINICAL SIGNIFICANCE: The selection of file systems in cleaning and shaping protocols is an enigma to endodontics. This in vitro study explored the selection protocols for the execution of root canal preparation. Heat treatment of nickel-titanium (NiTi) endodontic files had improved the cyclic fatigue resistance significantly enhancing the clinical life of file systems.

Evaluation of Nanomagnesium Oxide in Combination with Garlic Extract as an Endodontic Irrigant: An In Vitro Study.

AIM: The aim of this in vitro study was to evaluate the effectiveness of the combination of garlic extract in combination with magnesium oxide (MgO) for use as an endodontic irrigant at various contact times. MATERIALS AND METHODS: All 48 teeth were divided into 6 groups according to irrigation used after inoculation with Enterococcus faecalis and incubation. The control groups consisted of saline and sodium hypochlorite (NaOCl) used as irrigants and the test groups employed garlic extract combined with nano-magnesium oxide (nano-MgO) used as irrigant with two contact times, namely, 2 and 5 minutes, and garlic extract and nano-MgO used solely for 5 minutes each. Colony-forming units (CFUs) were counted after plating and incubation. RESULTS: In NaOCl, and in both combination groups, there was a significant reduction in CFU counts. The saline group showed no decrease. Statistical analysis showed no difference in efficacy between NaOCl and the two combination groups. There was a statistical difference between the combination group and garlic/nano-MgO alone at both 2 and 5 minutes. CONCLUSIONS: Under the conditions of this study, a novel irrigant, a combination of nanoparticles of MgO and garlic extract was as effective as NaOCl against E. faecalis in an in vitro model at two tested contact times. CLINICAL SIGNIFICANCE: Combination of MgO nanoparticles and garlic extract achieves disinfection comparable to gold standard NaOCl without harmful caustic effects of hypochlorite.

Effect of Heated Sodium Hypochlorite Irrigant on Structural Changes and Microhardness of Radicular Dentin: An In Vitro Study.

AIM: This study is aimed to evaluate the combined effect of sodium hypochlorite at varied concentrations and temperatures on radicular dentin microhardness along with its surface structural changes using an FTIR spectrometer. MATERIALS AND METHODS: Mandibular premolars were cleaned and shaped up to F3 Protaper gold rotary files, after which they were subjected to five experimental conditions - group I - neutral saline as negative control, group II - 3% NaOCl solution, group III - 5% NaOCl solution, group IV - 3% intracanal-heated NaOCl solution, and group V - 5% intracanal-heated NaOCl solution. Following this, the microhardness of radicular dentin at 100 µm and 300 µm from the canal lumen and Fourier-transform infrared (FTIR) spectroscopic analysis were performed. RESULTS: The results showed that intracanal-heated sodium hypochlorite group reduced root dentin microhardness at 300 µm than its nonheated counterpart. No difference in microhardness values was observed between 3% intracanal-heated and room-temperature sodium hypochlorite groups at 100 µm. Reduction in amide/phosphate ratio was noted in all the groups treated with sodium hypochlorite irrespective of temperature and concentration. CONCLUSION: Thus, considering that the level of alteration in physical and structural changes of root dentin with or without heating is insignificant, intracanal-heated low-concentration sodium hypochlorite solutions could be used as an alternative to high-concentration sodium hypochlorite. CLINICAL SIGNIFICANCE: Intracanal-heated low-concentration sodium hypochlorite enables the clinicians to achieve maximum disinfection while keeping the structural and physical properties of the dentin similar to room-temperature sodium hypochlorite.

Decision-making and challenges within the evolving treatment algorithm in spinal muscular atrophy: a clinical perspective.

INTRODUCTION: The clinical application of disease modifying therapies has dramatically changed the paradigm of the management of people with spinal muscular atrophy (SMA), from sole reliance on symptomatic care directed toward the downstream consequences of muscle weakness, to proactive intervention and even preventative care. AREAS COVERED: In this perspective, the authors evaluate the contemporary therapeutic landscape of SMA and discuss the evolution of novel phenotypes and the treatment algorithm, including the key factors that define individual treatment choice and treatment response. The benefits achieved by early diagnosis and treatment through newborn screening are highlighted, alongside an appraisal of emerging prognostic methods and classification frameworks to inform clinicians, patients, and families about disease course, manage expectations, and improve care planning. A future perspective of unmet needs and challenges is provided, emphasizing the key role of research. EXPERT OPINION: SMN-augmenting therapies have improved health outcomes for people with SMA and powered the practice of personalized medicine. Within this new proactive diagnostic and treatment paradigm, new phenotypes and different disease trajectories are emerging. Ongoing collaborative research efforts to understand the biology of SMA and define optimal response are critical to refining future approaches.

The outlook for individuals with Spinal Muscular Atrophy (SMA) has transformed with the approval of three effective disease modifying therapies in the past seven years. This group of genetic diseases that cause progressive muscle weakness and present as a broad range of severity ­ from mild disease with near normal lifespan to severe with abbreviated lifespan and comorbidities ­ now have gene-based therapies that have shown (motor) functional gains, ameliorated comorbidities, and improved overall quality of life of patients and prolonged survival. With the rapid translation of early diagnostic paradigms through newborn screening and the acceleration of a therapeutic pipeline, uncertainties within clinical practice arise including the optimal time to treat, the changing clinical characteristics of the treated population, monitoring of disease progression and therapeutic response in the post-treatment era. In this article, we review the evidence base to address these challenges. The key factors that determine individual treatment choice and response are discussed. The changed clinical characteristics in treated children that need early identification and appropriate management are discussed in depth. A new classification system in keeping with the changed paradigm is provided. In these early times of the treatment era, the evidence from clinical trials and real world is combined to generate evidence base to guide management. The reader would be apprised of the recent therapeutic developments, their applications, and outcomes. Finally, the challenges to be expected along the uncharted path of prolonged lifespan are discussed and care guidelines provided.

Political economy analysis of subnational health management in Kenya, Malawi and Uganda.

The need to bolster primary health care (PHC) to achieve the Sustainable Development Goal (SDG) targets for health is well recognized. In Eastern and Southern Africa, where governments have progressively decentralized health decision-making, health management is critical to PHC performance. While investments in health management capacity are important, so is improving the environment in which managers operate. Governance arrangements, management systems and power dynamics of actors can have a significant influence on health managers' ability to improve PHC access and quality. We conducted a problem-driven political economy analysis (PEA) in Kenya, Malawi and Uganda to explore local decision-making environments and how they affect management and governance practices for health. This PEA used document review and key informant interviews (N = 112) with government actors, development partners and civil societies in three districts or counties in each country (N = 9). We found that while decentralization should improve PHC by supporting better decisions in line with local priorities from community input, it has been accompanied by thick bureaucracy, path-dependent and underfunded budgets that result in trade-offs and unfulfilled plans, management support systems that are less aligned to local priorities, weak accountability between local government and development partners, uneven community engagement and insufficient public administration capacity to negotiate these challenges. Emergent findings suggest that coronavirus disease 2019 (COVID-19) not only resulted in greater pressures on health teams and budgets but also improved relations with central government related to better communication and flexible funding, offering some lessons. Without addressing the disconnection between the vision for decentralization and the reality of health managers mired in unhelpful processes and politics, delivering on PHC and universal health coverage goals and the SDG agenda will remain out of reach.

Evaluation of Effect of Natural Extract Sodium Gluconate on Smear Layer and Dentine Decalcification Compared with EDTA - An In-vitro Study.

OBJECTIVE: Mechanical instrumentation of the root canal system generates a smear layer on the canal walls which are removed most commonly with the help of chelators such as ethylenediaminetetraacetic acid (EDTA) but can potentially cause severe dentinal erosion. Considerable research has been conducted to find an al- ternative to EDTA which removes the smear layer without causing dentinal erosion. The current study aimed at evaluating the ability of sodium gluconate compared with that of 17% EDTA in smear layer removal along with its effect on dentine decalcification when used as a final irrigant. METHODS: Twenty single-rooted mandibular premolars were collected and prepared based on the pre-set criteria. Following preparation, the specimens were exposed to the test solutions as a final irrigant. Then the specimens were subjected to (Scanning electron microscope) SEM analysis at 1000x for evaluating the smear layer and 5000x for evaluating the dentinal erosion, and a Vickers microhardness tester was used for evaluat- ing the reduction in dentine microhardness post-treatment. The values obtained were analysed using SPSS software for a statistically significant difference with Mann-Whitney U test for evaluating of smear layer remov- al and dentinal erosion and using one-way (Analysis of variance) ANOVA test for microhardness evaluation. RESULTS: The smear layer removal capability of sodium gluconate was as effective as EDTA on the contrary so- dium gluconate did not cause any dentinal erosion compared to EDTA with a statistically significant difference (p=0.002 in middle third and p=0.001 in apical third of the canal). Microhardness reduction caused by sodium gluconate was less compared to EDTA, however, no statistically significant difference (p=0.113) was noted. CONCLUSION: Sodium gluconate, therefore, can produce a balance between smear layer removal and dentinal decalcification and can be considered a potential alternative to EDTA. (EEJ-2023-01-017).

Reinforced Immediate Dentin Sealing vs Conventional Immediate Dentin Sealing on Adhesive Behavior of Indirect Restorations: A Systematic Review.

AIM: The aim of this systematic review is to compare the bonding performance of indirect restoration with the reinforced immediate dentin sealing (IDS) method as opposed to the conventional IDS method. MATERIALS AND METHODS: A literature search was conducted in PubMed, Cochrane, and EBSCOHost up to January 31st 2022, accompanied by a hand search in Google Scholar. Inclusion criteria involved studies comparing conventional IDS and reinforced IDS protocol and evaluating various parameters influencing the bonding performance, such as type of indirect restoration, etching protocol, cavity design, tooth surface preparation, method of oral cavity simulation, and processing after luting. The quality of six included studies was appraised using CRIS guidelines. RESULTS: A total of 29 publications was identified, and 6 of them fulfilled the inclusion criteria. All of the included studies were in vitro studies. The predetermined data were independently extracted and evaluated by four reviewers. It was observed that most of the studies showed an improvement in bond strength with reinforced IDS when compared with conventional IDS. Also, etch-and-rinse and 2-step self-etch adhesive protocols have shown better bonding performance than universal adhesive systems. CONCLUSION: Reinforced IDS has similar or better bond strength to that of conventional IDS strategies. The need for prospective studies is highlighted. The future clinical studies for immediate dentin sealing ought to be reported in a uniform and methodological way. CLINICAL SIGNIFICANCE: Application of an additional layer of low-viscosity resin composite provides a thicker adhesive layer, prevents re-exposure of dentin during the final restoration, and allows a smoother preparation in lesser clinical chair time and eliminates any possible undercuts. Thus, reinforced IDS has shown to result in better preservation of the dentinal seal than IDS technique.

Fracture resistance of resin based and lithium disilicate endocrowns. Which is better? - A systematic review of in-vitro studies.

Objectives: The primary objective of this systematic review is to compare the fracture resistance of lithium disilicate (LDS)-based endocrowns and resin-based (RB) endocrowns of in-vitro studies, and the secondary objective is to compare their catastrophic failures. Materials and Methods: The review protocol was registered in the P ROSP ERO database (CRD42020166201). A comprehensive literature search was done in PubMed, Cochrane, EBSCOhost and Google Scholar using key terms. Only in-vitro studies that compared fracture resistance of LDS-based endocrowns and indirect RB endocrowns in molars were included. Data extraction, risk of bias assessment and qualitative analysis of the included studies were performed. Results: Five studies were included in this systematic review. The overall risk of bias for the included studies was moderate. Under axial loading, RB endocrowns showed similar fracture resistance when compared with LDS endocrowns. However, they showed better fracture resistance when compared with zirconia reinforced lithium silicate (ZLS) endocrowns. Furthermore, RB endocrowns showed fewer catastrophic failures than LDS-based endocrowns. Conclusions: RB endocrowns have similar or better fracture resistance and fewer catastrophic failures when compared to LDS-based endocrowns.

Assessing socio-economic profile of U-Reporters: Towards establishing a pool for equity analysis of future crowdsourced surveys.

BACKGROUND: Crowdsourcing was recognized as having the potential to collect information rapidly, inexpensively and accurately. U-Report is a mobile empowerment platform that connects young people all over the world to information that will change their lives and influence decisions. Previous studies of U-Report's effectiveness highlight strengths in the timeliness, low cost and high credibility for collecting and sending information, however they also highlight areas to improve on concerning data representation. EquityTool has developed a simpler approach to assess the wealth quintiles of respondents based on fewer questions derived from large household surveys such as Multiple Indicators Cluster Surveys (MICS) and Demographic and Health Surveys (DHS). METHODS: The methodology of Equity Tool was adopted to assess the socio-economic profile of U-Reporters (ie, enrolled participants of U-Report) in Bangladesh. The RapidPro flow collected the survey responses and scored them against the DHS national wealth index using the EquityTool methodology. This helped placing each U-Reporter who completed all questions into the appropriate wealth quintile. RESULTS: With 19% of the respondents completing all questions, the respondents fell into all 5 wealth quintiles, with 79% in the top-two quintiles and only 21% in the lower-three resulting in an Equity Index of 53/100 where 100 is completely in line with Bangladesh equity distribution and 1 is the least in line. An equitable random sample of 1828 U-Reporters from among the regular and frequent respondents was subsequently created for future surveys and the sample has an Equity Index of 98/100. CONCLUSIONS: U-Report in Bangladesh does reach the poorest quintiles while the initial recruitment skews to respondents towards better off families. It is possible to create an equitable random sub-sample of respondents from all five wealth quintiles and thus process information and data for future surveys. Moving forward, U-Reporters from the poorly represented quintiles may be incentivized to recruit peers to increase equity and representation. In times of COVID-19, U-Report in combination with the EquityTool has the potential to enhance the quality of crowdsourced data for statistical analysis.

Retention of pit and fissure sealants versus flowable composites in permanent teeth: A systematic review.

OBJECTIVE: To summarize the available clinical evidence on the relative effectiveness of retention of resin-based pit and fissure sealants (PFS) with that of flowable composites on occlusal surfaces of permanent teeth when evaluated in clinical trials. SOURCES: Electronic searches were performed in PubMed and Cochrane Library for the identification of relevant studies, from their inception until February 2020 and an additional search was done with the reference lists of included articles. STUDY SELECTION: The review protocol followed the PRISMA guidelines and was registered in PROSPERO (CRD42018112805). The risk of bias of the studies was independently appraised using the revised Cochrane Risk of Bias tool (RoB 2.0). DATA: Ten articles were considered relevant for qualitative synthesis. The data extracted from two of the included articles showed statistically significant difference between the two materials based on their retention potential, of which one article favored superior retention of flowable composites and one article favored higher retention of PFS and the other eight studies showed no significant difference between the two materials. CONCLUSION: The current review has shown evidence suggesting the effective retention of resin-based pit-and-fissure sealants and flowable composites when applied to prevent occlusal caries in permanent molars, however, this evidence is of low quality. Carefully designed long-term clinical trials are required to support the results of this review. CLINICAL SIGNIFICANCE: This is an important topic that would be of significant interest in the field of preventive dentistry, where sealants are the primary recommended method to prevent caries. The clinical efficacy of sealants is directly linked to their potential to retain and this systematic review focuses on comparing the relative effectiveness of resin-based pit-and-fissure-sealants with flowable composites in permanent teeth.

Smear Layer Removal and Microhardness Alteration Potential of a Naturally Occurring Antioxidant - An In Vitro Study.

INTRODUCTION: It is well-known in the field of endodontics that the presence of a smear layer in the root canals can harbor bacteria and limit the penetration of irrigating solutions and intracanal medications into the dentinal tubules which, in turn, causes the failure of endodontic treatment. Removing the entire smear layer throughout the root canal is essential for the success of endodontic treatment and these chemical agents that facilitate the removal of the smear layer are called chelating agents. Ethylenediaminetetraacetic acid (EDTA), being the most widely used chelating agent, brings about increased reduction in the microhardness of the root dentin, thereby making it friable. N-acetyl cysteine (NAC) is naturally occurring antioxidant that has various beneficial properties for the human being. Several studies have been done in determining the antimicrobial efficacy of NAC against various endodontic pathogens and concluded NAC to be advantageous. The chelating property of NAC has been utilized in heavy metal detoxification, where it binds to the metal ion and removes them from the human system. However, this chelating property has not been explored in the field of endodontics. AIM: This study was aimed to compare the ability of N-acetyl cysteine with the conventional chelating agent in the removal of the smear layer and in altering the microhardness of root dentin. MATERIALS AND METHODOLOGY: A total of 84 single-rooted human mandibular premolars with relatively similar dimension and morphology, freshly extracted with closed apices, were collected from adult patients. The crowns of all specimens were cut transversally at the cementoenamel junction (CEJ) with the double-faced diamond disc at low speed, with water coolant, to obtain a 12 mm root length. The root canals were randomly divided into three equal groups according to the final irrigation solutions: Group I: 17% EDTA, Group II: 20% NAC, and Group III: distilled water (control). They were then randomly divided into two parts: scanning electron microscope (SEM) analysis for the extent of smear layer removal and microhardness evaluation using the Vicker's hardness test. RESULTS: The smear layer removal ability of EDTA and NAC were more effective in the coronal and middle thirds of the root canal. However, both groups showed less smear layer removal in the apical region. Specimens treated with distilled water showed the least reduction in the smear layer throughout the length of the root canals. Regarding the evaluation of microhardness, both EDTA and NAC had a significant reduction in root dentin microhardness. However, the percentage of dentin microhardness reduction was significantly more in the EDTA group (p < 0.05) than N-acetyl cysteine in the coronal, middle, and apical third of the root canals. CONCLUSION: The chelating property of NAC is equally effective to that of EDTA in the smear layer from the root canal, and it induced a significantly lesser reduction in microhardness of root dentin than EDTA.

In vitro evaluation of five different herbal extracts as an antimicrobial endodontic irrigant using real time quantitative polymerase chain reaction.

CONTEXT: Sodium hypochlorite is the most commonly used irrigant but it has disadvantage like high cytotoxicity. So there is a need to find an alternative to 5.25% Sodium hypochlorite against microorganism Enterococcus faecalis and Candida albicans. Literature has shown that these 5 extracts namely Terminalia chebula, Myristica frangrans, Aloe barbadensis, Curcuma longa and Azadaricta indica has good properties which can be used as a potential endodontic irrigant. AIMS: To evaluate the antimicrobial efficacy of various herbal extracts namely Curcuma longa (CL), Azadiracta indica (AI), Aloe barbadensis (AV), Myristica fragrans (MF) and Terminalia chebula (TC) as endodontic irrigant against Enterococcus faecalis and Candida albicans using real-time quantitative polymerase chain reaction (qPCR). MATERIALS AND METHODS: Eighty-four teeth were extracted and suspended with Enterococcus faecalis and Candida albicans. A preliminary study was first performed to determine the minimum inhibitory concentration of extracts. The irrigating groups were divided into five herbal groups and 2 control groups. After irrigating the teeth the remaining microbial load was determined using qPCR. STATISTICAL ANALYSIS USED: Statistical analysis was performed using Oneway Anova/Kruskal-Wallis test with post-hoc Tukey's HSD and was statistically significant (P < 0.05). RESULTS: It was shown that Neem was highly efficient to 5.25% NaOCl in reducing Enterococcus faecalis and Candida albicans within the root canals when compared with other extracts. CONCLUSIONS: Neem leaf extract has a significant antimicrobial efficacy against Enterococcus faecalis and Candida albicans compared to 5.25% sodium hypochlorite.

CYP1A1 genotypes and haplotypes and risk of oral cancer: A case-control study in South Indians.

The CYP1A1 gene encodes for the enzyme, aryl hydrocarbon hydroxylase, which is involved in the biotransformation of various aromatic tobacco precarcinogens. In the present study, the association between CYP1A1 gene polymorphisms (IVS1-728G > A, Thr461Asn and Ile462Val), and the risk of oral cancer, was examined among 157 patients with oral cancer and 132 age-matched controls, in a south Indian population. The strength of the association between CYP1A1 variants and oral cancer was estimated by logistic regression. It was found that Thr461Asn was not polymorphic. Both IVS1-728G > A and Ile462Val frequencies were consistent with Hardy-Weinberg equilibrium in the control group. There were no significant differences in genotype or haplotype frequencies between controls and cases with oral cancer. Hence, CYP1A1 SNPs can be considered as not being associated with oral cancer at either the genotype or haplotype levels in the population studied.

An unlikely role for the NAT2 genotypes and haplotypes in the oral cancer of south Indians.

UNLABELLED: The arylamine N-acetyltransferase 2 (NAT2) enzyme detoxifies a wide spectrum of naturally occurring xenobiotics including carcinogens and drugs. Acetylation catalysed by the NAT2 is an important process in metabolic activation of arylamines to electrophilic intermediates that initiate carcinogenesis. Polymorphism in N-acetyltransferase 2 gene was reported to be associated with the susceptibility of various cancers. OBJECTIVE: The aim of our study was to determine whether there is any association between the susceptibility to oral cancer amongst the variations of NAT2 genotypes. DESIGN: This study was carried out in 157 patients with oral cancer. The control group consisted of 132 healthy volunteers. The most common polymorphisms rs1799929, rs1799930 and rs1799931 on the NAT2 gene were screened for the genotypes using TaqMan allelic discrimination. RESULTS: All the three SNPs were polymorphic with minor allele frequency of 0.339, 0.372 and 0.061 for rs1799929, rs1799930 and rs1799931, respectively. None of the polymorphic site deviated from HWE in controls. There were no significant differences in genotype or allele frequencies of three SNPs between controls and cases with oral cancer. Risk of oral cancer development for the carriers of the individual deduced phenotypes was also not statistically significant. Of the 3 studied polymorphisms, 2 were in strong LD and form one haplotype block. None of the haplotype had shown significant association with the oral cancer. CONCLUSIONS: Our study concludes that the NAT2 genotypes, phenotypes and haplotypes are not involved in the susceptibility to oral cancer in South Indian subjects.

Genetic polymorphisms of the CYP2E1 gene do not contribute to oral cancer susceptibility in south Indians.

Cytochrome P450 (CYP) is a super family of mixed-function oxidases that are responsible for the human metabolism of drugs and endogenous compounds, as well as environmental and dietary substances. Many CYP enzymes function in the liver, but presence of CYP2E1 in the brain is demonstrating its role in both nicotine and ethanol metabolism. To examine the association between CYP2E1 polymorphism and the risk of oral cancer, we performed a case-control study on a south Indian population. 157 patients with oral cancer and 132 age and sexmatched controls were recruited. Three SNPs of the CYP2E1 gene [4768G>A (p. V179I, dbSNP rs6413419), CYP2E1-1295G>C (dbSNP rs3813867) and CYP2E1_-1055C>T (dbSNP rs2031920)] were genotyped using TaqMan allelic discrimination. The V179I locus is monomorphic in the study subjects, whereas rs3813867 and rs2031920 are co-inherited with a minor allele frequency of 0.022. None of the polymorphic sites deviated from HWE in controls. A much lesser frequency of the uncommon c2 allele was seen in our control subjects than in Caucasians and East Asians. There were no significant differences between oral cancer and controls in the distribution of either allelic or genotype frequencies. None of the haplotypes showed a significant association with oral cancer. Our results suggest that CYP2E1 is not a major or independent determinant in the pathogenesis of oral cancer in south Indians.

Lack of association of EPHX1 genotypes and haplotypes with oral cancer in South Indians.

As genetic variation is thought to contribute to the etiology of oral cancer, microsomal epoxide hydrolase (EPHX1) was chosen as a candidate gene. This study thus sought to investigate possible genetic associations between the rs1051740, rs2292566, and rs2234922 polymorphisms of EPHX1 and oral cancer. Oral cancer patients (n=157) and healthy control subjects (n=132) were screened for the genotypes using TaqMan allelic discrimination. The associations between genotypes, alleles, and haplotypes of the three mutations and oral cancer were then analyzed using a case-control study. All the three single-nucleotide polymorphisms were polymorphic, with minor allele frequencies of 0.368, 0.249, and 0.232, respectively, for rs1051740, rs2292566, and rs2234922. None of the polymorphic sites deviated from Hardy-Weinberg equilibrium. There were no significant differences in genotype or allele frequencies of three single-nucleotide polymorphisms between controls and cases with oral cancer. Of the three studied polymorphisms, two were in strong linkage disequilibrium and formed one haplotype block. None of the haplotypes showed significant association with oral cancer. EPHX1 gene polymorphisms and haplotypes were not involved in the susceptibility to oral cancer in South Indian subjects.