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Jagjeet Kaur, 1 Vasudha Sambyal, 1 Kamlesh Guleria, 1 Neeti Rajan Singh, 2 Manjit Singh Uppal, 2 Mridu Manjari, 3 Meena Sudan 4 1Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University, Amritsar, India; 2Department of Surgery; 3Department of Pathology; 4Department of Radiotherapy, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, IndiaCorrespondence: Vasudha SambyalDepartment of Human Genetics, Guru Nanak Dev University, Amritsar 143001, Punjab, India Tel +911832258803-09 ext 3448Email vasudhasambyal@yahoo.co.inAim: The X-ray repair cross-complementing (XRCC) gene polymorphisms influence esophageal carcinogenesis by altering the DNA repair capacity. The present study was designed to screen five single nucleotide polymorphisms (SNPs) of XRCC genes for their susceptibility to esophageal cancer (EC) risk. There is no previous report on these polymorphisms for EC from India, where EC frequency is high.Methods: The present study included 497 subjects (213 EC patients and 284 healthy controls). The polymorphisms were screened using the PCR-RFLP method and allele and genotype distribution were compared using chi-square test. Association analysis was done by haplotype analysis and linkage disequilibrium (LD) analysis. Gene–gene interactions were identified using multifactor dimensionality reduction (MDR). The risk was calculated using binary logistic regression.Results: For XRCC1 p.Arg399Gln, a decreased risk for EC was associated with the AA genotype [OR (95% CI): 0.53 (0.3– 0.95), p=0.03] even after adjusting for various covariates [OR (95% CI): 0.49 (0.26– 0.9), p=0.024] and with the recessive model [OR (95% CI): 0.49 (0.27– 0.8), p=0.016]. The GA genotype of p.Arg280His was associated with an increased risk for EC [OR (95% CI): 1.7 (1.0– 2.82), p= 0.045] after adjustments. The two XRCC1 polymorphisms, p.Arg399Gln and p.Arg194Trp were in slight LD among EC patients (D̍́=0.845, r 2=0.042). XRCC2 and XRCC3 polymorphisms were not associated with EC risk.Conclusion: XRCC1 p.Arg399Gln plays a protective role in the development of the EC. The study is the first report from India, providing baseline data about genetic polymorphisms in DNA repair genes XRCC1, XRCC2 and XRCC3 modulating overall EC risk.Keywords: XRCC1, XRCC2, XRCC3, polymorphisms, esophageal cancer

Aims & Objectives: To evaluate dimensions of Sacral Rhomboid as predictors of CPD in Indian primigravidae and correlate it with clinical, external and ultrasonic pelvimetry. Material and method 300 uncomplicated primigravidae at 37 weeks & beyond underwent measurements of Height (ht), weight (wt), transverse (TD) & vertical diagonal (VD) of sacral rhomboid, external pelvimetry and Obstetric conjugate (OC) ultrasonically & pregnancy outcome studied. Results On the basis of outcome, patients were grouped into Gp1: No CPD, Gp2: CPD (LSCS due to CPD, instrumental delivery, Intrapartum stillbirth, birth injuries & asphyxia. CPD was found in 12%, associated significantly with older age, short stature & heavier babies. The sacral Rhomboid TD < 9.5 cm & VD < 10.5 cm increased the risk of CPD significantly by 7.5 & 2.5, respectively. The combination of (a) ht & TD (b) ht & VD (c) TD & VD further improved the predictive value & picked up 1 in 2 women with CPD. No significant correlation was found between external pelvimetry & CPD. Ultrasonic OC correlated well but was not found to be superior to sacral rhomboid dimensions. Conclusion This is a safe, simple method with a high predictive value and should be useful for screening for CPD in community. [ABSTRACT FROM AUTHOR]

Background: Pneumonia is an acute respiratory infection that has emerged as the predominant catalyst for escalating mortality rates worldwide. In the pursuit of the prevention and prediction of pneumonia, this work employs the development of an advanced deep-learning model by using a federated learning framework. The deep learning models rely on the utilization of a centralized system for disease prediction on the medical imaging data and pose risks of data breaches and exploitation; however, federated learning is a decentralized architecture which significantly reduces data privacy concerns., Methods: The federated learning works in a distributed architecture by sending a global model to clients rather than sending the data to the model. The proposed federated deep learning-based FedPneu computer-aided diagnosis model has been implemented in 2, 3, 4, and 5 clients architecture for early pneumonia detection using X-ray images. The key parameters configuration include batch size, learning rate, optimizer, decay, momentum, epochs, rounds, and random-split as 32, 0.0001, SGD, 0.000001, 0.9, 10, 100, and 42, respectively., Results: The results of the proposed federated deep learning-based FedPneu model have been provided in terms of round-wise accuracy, loss, and computational time. The highest accuracy of 85.632% has been achieved with 2-clients federated deep learning architecture, whereas, 3, 4, and 5 clients architecture achieved 85.536%, 76.112%, and 74.123% accuracies, respectively., Conclusion: In the proposed privacy-protected federated deep learning-based FedPneu model, the two-client architecture has been resulted as the most optimal framework for pneumonia detection among 3-clients, 4-clients, and 5-clients architecture. The model works in a collaborative and privacyprotected framework with a multi-silo dataset which could be highly beneficial for healthcare departments to maintain patient's data privacy with improved prediction outcomes.

Objectives: To evaluate a commercial a Congo Red urine devise for assessing preeclampsia risk., Study Design: Prospective non-intervention study among women presenting with clinical suspicion of preeclampsia. The devise was used at the time of enrolment and, depending on gestation, on 1-3 later occasions., Outcome Measures: Abnormal diffusion patterns classified as positive or negative, in relation to subsequent confirmation of preeclampsia (detection and false-positive rates, and predictive value) and the probability of diagnosis within a fixed time period (rule-in and rule-out)., Results: 600 women were enrolled in the study and follow-up information was available on 538, of whom 95 had preeclampsia at delivery and 443 did not. At enrolment the detection rate was 18 % and the false-positive rate 3.2 %; positive predictive value - probability of positive result being associated with preeclampsia - was 55 % and negative predictive value - probability of negative result not being preeclampsia - was 85 %. A positive test ruled-in delivery with preeclampsia within 28 days among 35 % and ruled-out preeclampsia with 7 days among 98 %. Repeat testing after enrolment yielded similar results to the initial sample., Conclusion: The test has screening potential although published studies differ in the observed detection rate. Using the test to rule-out preeclampsia within 7 days can provide a significant management advantage especially for triaging patients and selecting those who can be managed at the peripheral centres., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The study was conducted through an educational grant by PerkinElmer Inc who supplied the kits. Shuwen Biotech Co., Ltd. (Deqing County, Zhejiang Province, China) is the legal manufacturer of the Preeclampsia Detection Kit (Dot Blot Diffusion), the “Congo Red kit”. PerkinElmer Oy (Turku, Finland) was the distribution partner for Shuwen Biotech Co., Ltd in India., (Copyright © 2024. Published by Elsevier B.V.)

Lipid-based formulations (LbFs) have demonstrated success in pharmaceutical applications; however, challenges persist in dissolving entire doses of the drug into defined liquid volumes. In this study, the temperature-induced supersaturation method was employed in LbF to address drug loading and pill burden issues. Supersaturated LbFs (super-LbF) were prepared using the temperature-induced supersaturation method, where the drug load is above its equilibrium solubility. Further, the influence of the drug's physicochemical and thermal characteristics on drug loading and their relevance with an apparent degree of supersaturation (aDS) was studied using two model drugs, ibrutinib and enzalutamide. All the prepared LbFs were evaluated in terms of physical stability, dispersion, and solubilization capacity, as well as pharmacokinetic assessments. Drug re-crystallization was observed in the lipid solution on long-term storage at higher aDS values of 2-2.5. Furthermore, high-throughput lipolysis studies demonstrated a significant decrease in drug concentration across all LbFs (regardless of drug loading) due to a decline in the formulation solvation capacity and subsequent generation of in-situ supersaturation. Further, the in vivo results demonstrated comparable pharmacokinetic parameters between conventional LbF and super-LbF. The short duration of the thermodynamic metastable state limits the potential absorption benefits. However, super-LbFs of Ibr and Enz showed superior profiles, with 1.7-fold and 5.2-fold increased drug exposure compared to their respective crystalline suspensions. In summary, this study emphasizes the potential of temperature-induced supersaturation in LbF for enhancing drug loading and highlights the intricate interplay between drug properties, formulation characteristics, and in vivo performance., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Introduction: Diabetic retinopathy (DR), a microvascular complication of type 2 diabetes (T2D), results from complex interactions of genetic and environmental factors. Vascular endothelial growth factor (VEGF) and mouse model minute 2 (MDM2)are upregulated in the retina due to diabetes, which increases the risk of DR. VEGFA and MDM2 genetic variations can influence DR risk. The present case-control study was conducted to evaluate the association of VEGFA and MDM2 promoter variants with DR in a population from Punjab, Northwest India., Methods: A total of 414 DR patients, 425 T2D patients without DR, and 402 healthy controls were screened for VEGFA -2578C/A (rs699947), VEGFA -2549I/D (rs35569394), VEGFA -7C/T (rs25648), and MDM2 rs3730485 polymorphisms using polymerase chain reaction (PCR)-based methods., Results: VEGFA -2549 I allele (OR = 1.35 (1.00-1.81), p = 0.043) and II genotype (OR = 1.78 (1.00-3.15), p = 0.047) were significantly associated with increased risk of DR. VEGFA -7 CT genotype conferred reduced risk of DR (OR = 0.28 (0.20-0.38); p = <0.001). VEGFA -2578 and MDM2 rs3730485 showed no significant association with DR. A-I-T (OR = 0.30 (0.20-0.44); p = <0.001) and C-D-T (OR = 0.33 (0.16-0.65); p = 0.002) haplotypes of rs699947-rs35569394-rs25648 polymorphisms showed decreased risk of DR., Conclusions: I allele and II genotype of VEGFA -2549, CT genotype of VEGFA -7, and C-I-C and A-D-C haplotypes of rs699947-rs35569394-rs25648 polymorphisms were significantly associated with DR risk in a Northwest Indian population. This is the first study worldwide to report DR risk with VEGFA promoter variants together., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee of Guru Nanak Dev University issued approval Letter No. 573/HG, Dated- 29/03/2018. This study was approved by the Institutional Ethics Committee of Guru Nanak Dev University, Amritsar, Punjab, India (Letter No. 573/HG, Dated- 29/03/2018). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Buttar et al.)

Background & objectives Vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors which stimulates tumour progression induction of endothelial cell migration and division, inhibition of the apoptosis of endothelial cells, induction of serine protease activity and enhancement of vascular permeability. This study aimed to investigate the correlation of VEGF+405G/C,-7C/T and+936C/T polymorphisms with oesophageal cancer risk. Methods DNA samples of 464 subjects (231 sporadic oesophageal cancer affected individuals and 233 controls) were genotyped forVEGF+936C/T,+405G/C and-7C/T polymorphisms. VEGF+936C/T and +405G/C polymorphisms were genotyped by PCR-RFLP method whereas VEGF-7C/T polymorphism was genotyped using Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Results CT genotype of VEGF-7C/T polymorphism was significantly associated with reduced risk of oesophageal cancer. VEGF-7C/T polymorphism was significantly associated with reduced risk of oesophageal cancer underdominant, co-dominant, over dominant and log-additive genetic models in total patients and in the female group. C+936G+405T-7 haplotype was significantly associated with decreased risk (P=0.01)of oesophageal cancer in total patients and also in the male group (P=0.02). Interpretation & conclusions In future, replication of the findings of the present study in a larger sample from different ethnic groups, along with functional analysis, may be insightful for the role of VEGFA polymorphisms in the pathogenesis of oesophageal cancer. Identification of the correlation of VEGF variants with specific therapy in oesophageal cancer may help in better selection of patients and monitoring treatment response in VEGF-therapy.

Functional polymorphisms in the vascular endothelial growth factor (VEGF) alter the susceptibility toward different gastrointestinal tract (GIT) cancers. In this study, we explored the association of VEGF -2578C/A and VEGF -460T/C polymorphisms with esophageal cancer (EC) risk. In total, 330 patients with EC and 330 controls for VEGF -2578C/A polymorphism and 316 patients with EC and 316 controls for VEGF -460T/C polymorphism were genotyped. AA genotype ( p = 0.01) and A allele ( p = 0.02) of VEGF -2578C/A and CC genotype ( p = 0.04) and C allele ( p = 0.04) of VEGF -460T/C polymorphism were significantly associated with an increased risk of EC. VEGF -2578C/A and VEGF -460T/C polymorphisms have been studied in different GIT cancers, but results are inconclusive. Therefore, we performed a meta-analysis to assess the association of these polymorphisms with the risk of GIT cancers. The PubMed, ScienceDirect, and Google Scholar databases were used to search the articles. Twenty-one studies on VEGF -2578C/A and 20 studies on VEGF -460T/C polymorphism were included in this meta-analysis. VEGF -2578C/A polymorphism was associated with the decreased risk of GIT cancer in the overall population under the overdominant model ( p = 0.009). A significant association of VEGF -2578C/A polymorphism with GIT cancer risk has been observed in the middle easterners, Caucasians, and Asians under different genetic models. VEGF- 460T/C polymorphism was significantly associated with an increased risk of GIT cancers in Caucasians. Stratification of the data on the basis of cancer type showed a significant association of VEGF -2578C/A polymorphism with the risk of gallbladder cancer, whereas VEGF -460T/C polymorphism was associated with the risk of hepatocellular cancer, gastric cancer, and colorectal cancer. Our meta-analysis suggested that VEGF -2578C/A and VEGF -460T/C polymorphisms were associated with GIT cancer risk.

RAD51 is a highly conserved recombinase involved in the strand invasion/exchange of double-stranded DNA by homologous single-stranded DNA during homologous recombination repair. Although a majority of existing literature associates RAD51 with the pathogenesis of various types of cancer, recent reports indicate a role of RAD51 in maintenance of fertility. The present study reviews the role of RAD51 and its interacting proteins in spermatogenesis/oogenesis and additionally reports the findings from the molecular genetic screening of RAD51 135 G > C polymorphism in infertile cases and controls. Fifty-nine articles from PubMed and Google Scholar related to the reproductive role of RAD51 were reviewed. For case-control study, the PCR-RFLP method was used to screen the RAD51 135 G > C polymorphism in 201 infertile cases (100 males, 101 females) and 201 age- and gender-matched healthy controls (100 males, 101 females) from Punjab, North-West India. The review of literature shows that RAD51 is indispensable for spermatogenesis and oogenesis in animal models. Reports on the role of RAD51 in human fertility are limited, however it is involved in the pathogenesis of infertility in both males and females. Molecular genetic analyses in the infertile cases and healthy controls showed no statistically significant difference in the genotypic and allelic frequencies for RAD51 135 G > C polymorphism, even after segregation of the cases by type of infertility (primary/secondary). Therefore, the present study concluded that the RAD51 135 G > C polymorphism was neither associated with male nor female infertility in North-West Indians. This is the first report on RAD51 135 G > C polymorphism and infertility., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Micro RNAs are new diagnostic markers and therapeutic targets in breast cancer research. miR-107 and miR-126 have been reported to be linked with the pathogenesis of breast cancer. The present study investigates the levels of expression of miR-107 and miR-126 in patients with breast cancer to find their correlation with the risk of breast cancer in Amritsar, Punjab, Northwest India. Material and Methods: In total, 200 subjects, 100 patients with breast cancer and 100 controls, were enrolled to screen the expression of miR-107 and miR-126 using quantitative reverse transcription polymerase chain reaction (RT-PCR) technique. The Livak method (2 -ΔΔCt ) was used to calculate the fold change of the expression of micro RNAs. Student t -test was used to calculate the significant change in the expression of miRNAs in patients as compared with controls. Spearman rank correlation coefficient and ROC were conducted. The value of p < 0.05 was considered to indicate a statistically significant difference. Results: miR-107 was downregulated in patients with breast cancer as compared with controls (fold change = 0.467; p = 0.114) but not statistically significant. The expression of miR-126 was found to be 5.37 times elevated in patients with breast cancer, specifically in stage I and stage III patients ( p = 0.009), compared with controls, which may indicate its oncogenic activity. The ROC analyses revealed that miR-126 could be a potential diagnostic marker. In conclusion oncogenic behavior of miR-126 is suggestive of its role in pathogenesis in patients with breast cancer.

XRCC1 is involved in repair of single-strand breaks generated by mutagenic exposure. Polymorphisms within XRCC1 affect its ability to efficiently repair DNA damage. Polycyclic aromatic hydrocarbons or PAHs are genotoxic compounds which form bulky DNA adducts that are linked with infertility. Few reports suggest combined role of XRCC1 polymorphisms and PAHs in infertility. Present study investigates association of three XRCC1 polymorphisms (p.Arg194Trp, p.Arg280His, p.Arg399Gln) with male and female infertility in a North-West Indian population using case-control approach. Additionally, in silico approach has been used to predict whether XRCC1 polymorphisms effect interaction of XRCC1 with different PAHs. For case-control study, XRCC1 polymorphisms were screened in peripheral blood samples of age- and gender-matched 201 infertile cases (♂-100, ♀-101) and 201 fertile controls (♂-100, ♀-101) using PCR-RFLP method. For in silico study, AutoDock v4.2.6 was used for molecular docking of B[a]P, BPDE-I, ( ±)-anti-BPDE, DB[a,l]P, 1-N, 2-N, 1-OHP, 2-OHF with XRCC1 and assess effect of XRCC1 polymorphisms on their interaction. In case-control study, statistical analysis showed association of XRCC1 p.Arg280His GA genotype (p = 0.027), A allele (p = 0.019) with reduced risk of male infertility. XRCC1 p.Arg399Gln AA genotype (p = 0.021), A allele (p = 0.014) were associated with reduced risk for female primary infertility. XRCC1 p.Arg194Trp T allele was associated with increased risk for female infertility (p = 0.035). In silico analysis showed XRCC1-PAH interaction with non-significant effect of XRCC1 polymorphisms on predicted binding. Therefore, present study concludes that XRCC1 polymorphism-modified risk for male and female infertility in North-West Indians without significant effect on predicted XRCC1-PAH interactions. This is the first report on XRCC1 in female infertility., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In India, esophageal cancer (EC) is among the major cause of cancer-related deaths in both sexes. In recent past, autophagy has emerged as one of the crucial process associated with cancer. In the development of EC, the role of autophagy and the precise molecular mechanism involved has yet to be fully understood. Recently, a small number of studies have proposed how variations in autophagy genes affect the growth and development of EC. Micro-RNA's are also known to play a critical role in the development of EC. Here, we examined the relationship between the risk of EC and two single-nucleotide polymorphisms (SNPs) in the key autophagy genes, ATG10 rs1864183 and ATG16L1 rs2241880. We also analyzed the association of miR-107 and miR-126 with EC as these miRNA's are associated with autophagy., Methods and Results: A total of 230 EC patients and 230 healthy controls from North-west Indian population were enrolled. ATG10 rs1864183 and ATG16L1 rs2241880 polymorphism were analyzed using TaqMan genotyping assay. Expression levels of miR-107 and miR-126 were analyzed through quantitative PCR using SYBR green chemistry. We found significant association of CT + CC genotype (OR 0.64, p = 0.022) in recessive model for ATG10 rs1864183 polymorphism with decreased EC risk. For ATG16L1 rs2241880 polymorphism significant association for AG genotype (OR 1.48, p = 0.05) and G allele (OR 1.43, p = 0.025) was observed for increased EC risk. Expression levels of miR-126 were also found to be significantly up regulated (p = 0.008)., Conclusion: Our results suggest that ATG10 rs1864183, ATG16L1 rs2241880 and miR-126 may be associated with esophageal carcinogenesis and warrant further investigation., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

A disease is an abnormal condition that negatively impacts the functioning of the human body. Pathology determines the causes behind the disease and identifies its development mechanism and functional consequences. Each disease has different identification methods, including X-ray scans for pneumonia, covid-19, and lung cancer, whereas biopsy and CT-scan can identify the presence of skin cancer and Alzheimer's disease, respectively. Early disease detection leads to effective treatment and avoids abiding complications. Deep learning has provided a vast number of applications in medical sectors resulting in accurate and reliable early disease predictions. These models are utilized in the healthcare industry to provide supplementary assistance to doctors in identifying the presence of diseases. Majorly, these models are trained through secondary data sources since healthcare institutions refrain from sharing patients' private data to ensure confidentiality, which limits the effectiveness of deep learning models due to the requirement of extensive datasets for training to achieve optimal results. Federated learning deals with the data in such a way that it doesn't exploit the privacy of a patient's data. In this work, a wide variety of disease detection models trained through federated learning have been rigorously reviewed. This meta-analysis provides an in-depth review of the federated learning architectures, federated learning types, hyperparameters, dataset utilization details, aggregation techniques, performance measures, and augmentation methods applied in the existing models during the development phase. The review also highlights various open challenges associated with the disease detection models trained through federated learning for future research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Understanding the mechanisms underlying the dispersion and digestion process is vital in the development of oral lipid-based formulations (LBFs). In vitro lipolysis models mimic the digestion process in the stomach and intestine to explore the fundamental mechanism of supersaturation, solubilization, and precipitation of drugs within the LBFs. The lipid digestion is controlled by the in vitro experimental conditions, and constitution of the lipid formulations. Hence, there is a continuous upgradation in the digestion models to best extrapolate the in vivo conditions. This review covers the recent developments in digestion models with media compositions and lipid formulation components. Key findings from recent studies that thoroughly examined the relation between the digestion, solubilization, and permeation of oral LBFs in the presence of bile-lipid aggregates are presented. These developments are foremost to build the in vitro-in vivo correlation of the drugs for regulatory considerations., Competing Interests: Declaration of Competing Interest None of the authors have potential conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: As the pregnancy advances beyond term, the risk of perinatal morbidity and mortality increases. Hence to prevent these complications associated with postterm pregnancy, induction of labor is done, as per our institution protocol between 40 and 41 weeks of gestation. Induction has its own drawback, so it is essential to identify the women with high chances of failure of induction of labor, to prevent the morbidities associated with induction failure., Aim: To study the role of ultrasonographic fetal adrenal gland enlargement for the prediction of success of labor induction among primigravida beyond 40 weeks gestation., Material and Methods: Low-risk primigravidas beyond 40 weeks gestation, scheduled for induction of labor, were enrolled for the study. Fetal adrenal gland dimensions were measured by using abdominal probe Philips HD 7XE and general electronics logiq P6 pro or any ultrasound machine equipped with 7.5-10 MHz linear array probe and 3.5-5 MHz curved array probe., Results: The fetal adrenal gland length, width and ratio were statistically significant between the successful versus failed induction groups. The cutoff fetal zone ratio > 0.36 for the prediction of successful induction of labor had 90% sensitivity, 89% specificity, 93% PPV and 75% NPV., Conclusion: Fetal zone enlargement (fetal zone ratio > 0.36) is a strong predictor of successful induction of labor as compared to TVL and Bishop's score. It can be used for screening the women, who are destined for induction failure, so that adverse effects of induction of labor can be avoided., Competing Interests: Disclosure of Potential Conflict of InterestNone., (© Federation of Obstetric & Gynecological Societies of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: The present study aimed to investigate the potential association of VEGF-116G/A promoter polymorphism with esophageal cancer risk in North-West Indians and to perform a comprehensive meta-analysis of VEGF-116G/A polymorphism in Gastrointestinal Tract (GIT) cancers., Methods: A total of 679 DNA samples (333 esophageal cancer patients and 346 healthy controls) were genotyped for VEGF-116G/A polymorphism using Sanger sequencing. In silico analysis was carried out to predict the impact of VEGF-116G/A polymorphism on transcription factor binding sites. Ten studies including 2157 patients and 2307 controls on different GIT cancers were included in the meta-analysis.  Results: The AA genotype and A allele of VEGF -116G/A polymorphism was significantly associated with an increased risk of esophageal cancer. In silico analysis predicted that A allele of VEGF-116G/A polymorphism created new binding sites for STAT4, c-Ets-1 and Elk-1 transcription factors. The meta-analysis results showed that VEGF-116G/A polymorphism was associated with an increased risk of GIT cancer under the recessive and AA vs GG genetic model in the overall population. Stratification of the studies by ethnicity revealed an increased risk of GIT cancers in Asians under allele contrast, recessive, AA vs GG and AA vs AG model. Analysis based on cancer type revealed an increased risk of esophageal cancer under allele contrast, recessive, AA vs GG and AA vs AG comparison model and increased risk of oral cancer was observed under the allele contrast model and dominant model., Conclusion: VEGF-116G/A polymorphism was associated with esophageal cancer risk in North- West Indians. The findings of the present meta-analysis showed a significant association of VEGF-116G/A polymorphism with GIT cancer risk.

Background: DNA repair genes are among the low-penetrance genes implicated in breast cancer. However variants of DNA repair genes may alter their protein function thus leading to carcinogenesis. Breast cancer is the most common cancer among women in India. The aim of the present study was to identify association, if any, of single nucleotide polymorphisms (SNP's) in four genes involved in DNA repair pathways including, RAD51 rs1801320, XRCC1 rs25487, XRCC2 rs3218536, and XRCC3 rs861539 with the risk of breast cancer. Materials and Methods: In this case-control study 611 female subjects (311 breast cancer patients and 300 healthy controls) were screened for four SNPs using polymerase chain reaction-restriction fragment length polymorphism analyses. Multifactor dimensionality reduction (MDR) analysis was performed to estimate the gene-gene interaction. Protein-protein interaction network analysis were studied using the STRING database. Results: The GC genotype ( p  = 0.018) and the combined GC+CC ( p  = 0.03) genotypes of RAD51 rs1801320 were significantly associated with reduced risk of breast cancer. The CT genotype ( p  = 0.0001), the combined CT+TT genotypes ( p  = 0.0002), and the T allele ( p  = 0.0019) of XRCC3 rs861539 polymorphism were associated with reduced risk of the breast cancer. No association of XRCC1 rs25487 and XRCC2 rs3218536 polymorphisms with breast cancer was observed. MDR analysis indicated a positive interaction between XRCC3 and XRCC2 . String network analysis showed that the RAD51, XRCC1, XRCC2, and XRCC3 proteins are in strong interaction with each other and other breast cancer-related proteins such as BRCA2. Conclusion: RAD51 rs1801320 and XRCC3 rs861539 polymorphisms were associated with reduced risk of breast cancer. There is evidence of positive interactions among XRCC1 , XRCC2 , XRCC3 , and RAD51 .