Patient Reported Outcome Measures used in Surgical Evaluation of Obstructive Sleep Apnea: A Systematic Review.

OBJECTIVE: To identify patient-reported outcome measures (PROMs) used to measure adult obstructive sleep apnea (OSA)-related quality of life in sleep surgery and analyze key psychometric properties in the original design and development of each PROM. DATA SOURCES: PubMed, Web of Science, Embase, PsychINFO, and CINAHL. REVIEW METHODS: A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Disease-specific instruments assessing sleep-related quality of life that were used in sleep surgery studies and validated in patients with sleep disorders were included. The Consensus-based Standards for the Selection of Health Status Measurement Instruments (COSMIN) criteria were used to evaluate methodological quality. RESULTS: A total of 2494 abstracts were retrieved, and 216 underwent full-text review. Seven PROMs assessing sleep-related quality of life were identified. Only one (14%) PROM (SAQLI) was developed using both patient and physician input, and none were rated as "adequate" for content validity. Two PROMs utilized patients with sleep-disordered breathing during content development and none specifically queried patients considering surgery. Six (86%) PROMs demonstrated "very good" analysis of internal consistency per COSMIN criteria, and six (86%) included data on test-retest reliability. CONCLUSION: Several PROMs are utilized in sleep-related quality-of-life assessments for patients treated with OSA surgery. The measurement properties of these PROMs are of variable quality, and notably, no PROMs meet adequate quality measurements for content validity. New and updated PROMs for OSA-related quality of life should consider input from sleep surgery patients and providers. Laryngoscope, 2024.

Analysis of Internet-Based Written Materials on Surgery for Obstructive Sleep Apnea.

Objective: Obstructive sleep apnea (OSA) has many treatment options and the Internet is an important resource for patients. The quality of information reviewed by patients about sleep surgery is unknown. We assessed readability, accessibility, actionability, and quality of online content for OSA surgeries. Study Design: Review of webpages by 2 independent reviewers. Setting: Internet-based search. Methods: We queried Google for sleep apnea surgery and included top 100 English language webpages. Content was scored by 2 reviewers using the Flesch-Kincaid (FK), Simple Measure of Gobbledygook (SMOG), JAMA benchmarks, CDC Clear Communication Index (CCI), and Patient Education Materials Assessment Tool (PEMAT) understandability and actionability scores. Results: Eighty-seven webpages were evaluated including 40 hosted by academic hospitals, 23 private practices, 10 general knowledge, 4 national organizations, 3 industry, 3 non-profit hospitals, and 2 government-sponsored. Mean CCI ranged from 22.7% to 84.9%. No sources met the 90% CCI cutoff. Average PEMAT understandability score was 80.4% (±7.8; 62.5%-93.3%), with 91% meeting the 70% standard score. Average PEMAT-actionability score was 38.4% (±16.5; 0%-70%), with 5% meeting the standard score. The average readability of webpages was the 10th grade reading level. Only 5% of pages met the recommended 6th grade reading level or lower. Only 21% of pages addressed surgical risks. Conclusion: Most online resources regarding OSA surgery do not meet recommended standards for communication. Providers should be aware of limitations of materials when counseling patients on sleep surgery treatments. Future patient education resources should meet health communication and readability standards.

Electrocochleography-Based Tonotopic Map: II. Frequency-to-Place Mismatch Impacts Speech-Perception Outcomes in Cochlear Implant Recipients.

OBJECTIVES: Modern cochlear implants (CIs) use varying-length electrode arrays inserted at varying insertion angles within variably sized cochleae. Thus, there exists an opportunity to enhance CI performance, particularly in postlinguistic adults, by optimizing the frequency-to-place allocation for electrical stimulation, thereby minimizing the need for central adaptation and plasticity. There has been interest in applying Greenwood or Stakhovskaya et al. function (describing the tonotopic map) to postoperative imaging of electrodes to improve frequency allocation and place coding. Acoustically-evoked electrocochleography (ECochG) allows for electrophysiologic best-frequency (BF) determination of CI electrodes and the potential for creating a personalized frequency allocation function. The objective of this study was to investigate the correlation between early speech-perception performance and frequency-to-place mismatch. DESIGN: This retrospective study included 50 patients who received a slim perimodiolar electrode array. Following electrode insertion, five acoustic pure-tone stimuli ranging from 0.25 to 2 kHz were presented, and electrophysiological measurements were collected across all 22 electrode contacts. Cochlear microphonic tuning curves were subsequently generated for each stimulus frequency to ascertain the BF electrode or the location corresponding to the maximum response amplitude. Subsequently, we calculated the difference between the stimulus frequency and the patient's CI map's actual frequency allocation at each BF electrode, reflecting the frequency-to-place mismatch. BF electrocochleography-total response (BF-ECochG-TR), a measure of cochlear health, was also evaluated for each subject to control for the known impact of this measure on performance. RESULTS: Our findings showed a moderate correlation (r = 0.51; 95% confidence interval: 0.23 to 0.76) between the cumulative frequency-to-place mismatch, as determined using the ECochG-derived BF map (utilizing 500, 1000, and 2000 Hz), and 3-month performance on consonant-nucleus-consonant words (N = 38). Larger positive mismatches, shifted basal from the BF map, led to enhanced speech perception. Incorporating BF-ECochG-TR, total mismatch, and their interaction in a multivariate model explained 62% of the variance in consonant-nucleus-consonant word scores at 3 months. BF-ECochG-TR as a standalone predictor tended to overestimate performance for subjects with larger negative total mismatches and underestimated the performance for those with larger positive total mismatches. Neither cochlear diameter, number of cochlear turns, nor apical insertion angle accounted for the variability in total mismatch. CONCLUSIONS: Comparison of ECochG-BF derived tonotopic electrode maps to the frequency allocation tables reveals substantial mismatch, explaining 26.0% of the variability in CI performance in quiet. Closer examination of the mismatch shows that basally shifted maps at high frequencies demonstrate superior performance at 3 months compared with those with apically shifted maps (toward Greenwood and Stakhovskaya et al.). The implications of these results suggest that electrophysiological-based frequency reallocation might lead to enhanced speech-perception performance, especially when compared with conventional manufacturer maps or anatomic-based mapping strategies. Future research, exploring the prospective use of ECochG-based mapping techniques for frequency allocation is underway.

Comparison of Chronic Sialadenitis Symptom Burden in Patients With Sialolithiasis Versus Stenosis Before and After Sialendoscopy.

OBJECTIVE: To define symptomatology and responses to treatment in chronic sialadenitis from sialolithiasis versus duct stenosis and establish a minimal clinically significant difference (MCID) in the validated Obstructive Salivary Problem Impact Test (SPIT). STUDY DESIGN: Prospective, cohort. SETTING: Tertiary-care center. METHODS: Patients completed the SPIT questionnaire at presentation and 3 to 6 months after surgery. SPIT scores and domains were compared between patients with symptomatic sialolithiasis and those with stenosis of a major salivary gland. RESULTS: Seventy-nine patients completed the SPIT, including 43 (54%) with sialolithiasis and 36 (46%) with stenosis. Stenosis patients displayed greater baseline scores compared to sialolithiasis patients (45.4 ± 19.9 vs 33.3 ± 18.5, P < .013). Frequency and severity of gland swelling and pain (21.9 ± 8.9 vs 17.1 ± 9.6, P = .02) and functional/psychosocial impact subscores were greater in the stenosis versus sialolithiasis groups (18.0 ± 10.9 vs 11.3 ± 9.4, P < .01). For 43 patients who underwent surgical intervention, SPIT scores improved at 3 to 6 months postoperatively in all domains (-18.6 ± 19.4, P < .01). Degree of improvement did not differ between sialolithiasis versus stenosis groups (-22.0 ± 20.9 vs -13.3 ± 15.8, P = .13). The MCID in SPIT score was found to be -13 points. A postoperative SPIT score of less than 10 suggested symptom resolution. CONCLUSION: When compared to sialolithiasis, chronic salivary obstruction from stenosis is associated with greater baseline SPIT scores, indicating poorer sialadenitis-related quality of life due to greater symptom frequency and functional impact. Based on SPIT survey outcomes, a score decrease of 13 points or SPIT score <10 represent significant symptom improvement.

Sociodemographic and Healthcare System Barriers to PAP Alternatives for Adult OSA: A Scoping Review.

OBJECTIVE: To investigate sociodemographic and healthcare system barriers to access and utilization of alternative treatments to positive airway pressure (PAP) in the management of adult obstructive sleep apnea (OSA). DATA SOURCES: PubMed, Embase, and Web of Science databases were searched from 2003 to 2023 for English-language studies containing original data on sociodemographic and healthcare system barriers to PAP-alternative treatments for adult OSA. REVIEW METHODS: Studies were assessed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. Title and abstract screening, full-text review, and data collection were conducted by two investigators independently. RESULTS: Out of 1,615 studies screened, 13 studies met inclusion criteria and reported on a total of 1,206,115 patients who received PAP alternative treatments, including surgery (n = 9 studies), and oral appliances (OAs) (n = 3 studies). The chance of receiving a PAP-alternative treatment such as surgery was greater among patients aged 39 years or younger, had body mass index below 30 kg/m2, fewer comorbidities, private insurance, and a higher occupational and income status. The decision of individuals to receive PAP alternative treatments was influenced by increased patient education from providers, as well as improvements in daytime sleepiness and partner perception of snoring and apnea. CONCLUSION: Cumulative evidence suggests that several sociodemographic and healthcare system factors are associated with decreased use of PAP alternatives when PAP therapy fails. Investigation of interventions to eliminate these potential barriers may improve access and treatment outcomes. Laryngoscope, 2024.

Associations between telomere attrition, genetic variants in telomere maintenance genes, and non-small cell lung cancer risk in the Jammu and Kashmir population of North India.

BACKGROUND: Telomeres are repetitive DNA sequences located at the ends of chromosomes, playing a vital role in maintaining chromosomal integrity and stability. Dysregulation of telomeres has been implicated in the development of various cancers, including non-small cell lung cancer (NSCLC), which is the most common type of lung cancer. Genetic variations within telomere maintenance genes may influence the risk of developing NSCLC. The present study aimed to evaluate the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India, and to investigate the relationship between telomere length and NSCLC risk. METHODS: We employed the cost-effective and high-throughput MassARRAY MALDI-TOF platform to assess the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India. Additionally, we used TaqMan genotyping to validate our results. Furthermore, we investigated telomere length variation and its relation to NSCLC risk in the same population using dual-labeled fluorescence-based qPCR. RESULTS: Our findings revealed significant associations of TERT rs10069690 and POT1 rs10228682 with NSCLC risk (adjusted p-values = 0.019 and 0.002, respectively), while TERF2 rs251796 and rs2975843 showed no significant associations. The TaqMan genotyping validation further substantiated the associations of TERT rs10069690 and rs2242652 with NSCLC risk (adjusted p-values = 0.02 and 0.003, respectively). Our results also demonstrated significantly shorter telomere lengths in NSCLC patients compared to controls (p = 0.0004). CONCLUSION: This study highlights the crucial interplay between genetic variation in telomere maintenance genes, telomere attrition, and NSCLC risk in the Jammu and Kashmir population of North India. Our findings suggest that TERT and POT1 gene variants, along with telomere length, may serve as potential biomarkers and therapeutic targets for NSCLC in this population. Further research is warranted to elucidate the underlying mechanisms and to explore the potential clinical applications of these findings.

Cisplatin-based combination therapy for cancer.

Cisplatin, that is, cis-diamminedichloroplatinum is a coordinate compound that is mainly preferred as prior treatment against several solid tumors and malignancies like ovaries, head and neck, testicular, and lung cancers because of its anticancer activity. Cisplatin binds at the N7 position of purine and forms adducts, leading to altered activity of DNA that triggers apoptosis. DNA damage is followed by several signaling pathways like induced oxidative stress, upregulated p53, mitogen-activated protein kinase (MAPK), and Jun N-terminal kinases (JNK) or Akt pathways along with induced apoptosis. Additionally, cisplatin treatment comes with few disadvantages such as toxic effects, that is, hepatotoxicity, cardiotoxicity, neurotoxicity, etc., and drug resistance. Furthermore, to overcome cisplatin resistance and toxicological effects, combination drug therapy has been considered. The aim of the review is to focus on the molecular mechanism of action of cisplatin and combination drug therapy to reduce the side effects in cancer therapy.

Genetic analysis of polymorphism rs10937405 of TP63 gene in breast and ovarian cancer patients of North Indian Cohort.

Introduction: Ovarian and breast cancers are highly prevalent in the population of Jammu and Kashmir (J&K). However, case-control association studies on breast and ovarian cancers are lacking in this population. Moreover, no case-control study is available on variant rs10937405 of TP63 in breast and ovarian cancers. Thus, we designed to replicate the cancer susceptible variant rs10937405 of TP63 in ovarian and breast cancers in the population of J&K because the TP63 gene act as a tumor suppressor gene and was previously associated with various cancers. Materials and Methods: This case-control association study conducted at the Shri Mata Vaishno Devi University, includes 150 breast, 150 ovarian cancer cases, and 210 healthy controls (age and sex-matched). Variant rs10937405 of the TP63 gene was determined by the TaqMan assay. Hardy-Weinberg equilibrium for the variant was assessed using the Chi-square test. The allele and genotype-specific risks were estimated by odds ratios (ORs) with 95% confidence intervals (CI). Results: In this study, variant rs10937405 of TP63 gene did not show any risk with ovarian and breast cancer with (P-value = 0.70) having OR 0.94, (0.69-1.28 at 95% CI) and (P-value = 0.16) having OR 0.80, (0.59-1.10). Discussion: Our results indicate that the variant rs10937405 of the TP63 gene did not impart any risk of breast and ovarian cancer in the population of J&K. Our results indicate that a larger sample size is needed for further statistical validation. As the study was for a particular variant, it warrants the analysis of other variants of this gene.

Evolution of Pulmonary Valve Management During Repair of Tetralogy of Fallot: A 14-year Experience.

BACKGROUND: The optimal repair strategy for tetralogy of Fallot remains controversial. This report presents a 14-year evolution of management of the pulmonary valve (PV) from transannular patch to valve-sparing repair to neovalve creation using living right atrial appendage tissue. METHODS: A retrospective review of 172 consecutive patients undergoing complete repair for TOF between January 2007 and June 2021 was performed. Clinical and follow-up data were analyzed by repair group. Neopulmonary valve (NPV) creation using right atrial appendage tissue was introduced in 2019. Failure of valve-sparing repair was defined as needing reintervention for recurrent right ventricular outflow tract obstruction (RVOTO). RESULTS: Median age and weight at repair were 4.9 months and 6 kg, respectively. Median preoperative PV size and z-score were 6.4 mm (5.2-8.3 mm) and -3.2 (-4.1 to -2.1), respectively. Patients who underwent valve-sparing repair had larger PV size and z-score compared with patients who underwent transannular patch procedures (8 mm vs 5.6 mm; -2.1 vs -3.2; both P < .001). There were no hospital mortalities. Overall follow-up was 44 months. At last follow-up, 10% of patients who underwent valve-sparing repair had repeat intervention for recurrent RVOTO. Patients who had failed valve-sparing repair had significantly lower PV z-scores (-2.6 vs -1.9; P = .01). An NPV was used in 8 patients with a median PV z-score of -4 (-4.7 to -3.9). At 6 months, 6 patients (75%) had mild or trivial pulmonary insufficiency after NPV placement. CONCLUSIONS: Repair of tetralogy of Fallot is a safe operation with excellent outcomes. Valve-sparing repair avoids right ventricular dilation but may fail for RVOTO at a PV z-score <-2. NPV creation offers an alternative option in patients with a small PV.

Genetic association of ARID5B with the risk of colorectal cancer within Jammu and Kashmir, India.

Colorectal cancer (CRC), which includes the development of cancer from the colon or rectum, is one of the highly prevalent cancers in the populations of Jammu and Kashmir (J&K) in India. However, case-control genetic association studies on CRC are lacking in this population. Various genome-wide association studies have previously shown that single-nucleotide polymorphisms (SNPs) of the AT-rich interaction domain 5B (ARID5B) gene located on chromosome 10q21.2 contribute substantially to the development of colorectal cancer. The association between ARID5B and CRC risk in north Indian population groups is still unknown. To understand the role of ARID5B SNPs in CRC in the population of J&K, we designed a case-control study to investigate the association of the cancer susceptibility variant rs10740055 of ARID5B with CRC in the population of J&K. The study included 180 cases and 390 healthy controls. Genotyping of the rs10740055 variant was performed by RT-PCR using the TaqMan assay technique. Hardy-Weinberg equilibrium of the variant was assessed using the chi-squared test. The allele- and genotype-specific risks were estimated by odds ratios (ORs) with 95% confidence intervals (CIs). The rs10740055 variant showed a higher risk for colorectal cancer with an OR of 3.35 (1.99-5.65 at 95% CI) and P = 0.000005 corrected for age, gender, ethnicity, BMI, alcohol intake and smoking. Our results indicate that the A allele of rs10740055 imparts risk to the population and also that a larger sample size is needed for further statistical validation. The association of other variants in other ARID family genes should also be tested as their role cannot be ruled out.

REV3L single nucleotide variants lead to increased susceptibility towards non-small cell lung cancer in the population of Jammu and Kashmir.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common lung cancer, accounting for 80-85% of all lung cancer cases. Various genetic studies have associated REV3L (Protein reversion less 3-like) gene mutations, which encodes the catalytic subunit of error prone translesion synthesis polymerase zeta with cancer, including lung cancer; however, no such data is available from any North Indian population. In this study we attempted to screen the North Indian population of Jammu and Kashmir (J&K) for the potential role of REV3L gene polymorphisms in NSCLC. METHODS: A total of four REV3L single nucleotide variants were selected for genotyping based on the available literature. The genotyping was carried out by using the TaqMan allele discrimination assay in 500 subjects (200 NSCLC patients and 300 age and sex matched healthy controls). The association of variants with NSCLC was evaluated by logistic regression. RESULTS: Out of the four REV3L variants genotyped; rs1002481, rs462779, and rs465646 were found significantly associated with NSCLC risk under the recessive model, with an Odds Ratio (OR) of 3.52(2.14-5.8 at 95% CI, p-value = 0.00000062), 3.7 (1.8-7.6 at 95% CI, p-value = 0.00031), and 2.2 (1.47-3.37 at 95% CI, p-value = 0.0003), respectively. DISCUSSION: Our data supports a strong association between variants rs1002481, rs462779, rs465646 and NSCLC, indicating a potential role of these REV3L variants in increasing the risk for the development of NSCLC in the studied population. Although a first report from any Indian population, these variants have been previously reported to be associated with lung and colorectal cancers in different world populations. Our data along with the existing data supports the notation that these variants can be used as potential genetic predisposition markers. AVAILABILITY OF DATA AND MATERIALS: Data generated and analysed during study is not available publicly but can be made available from the corresponding author upon reasonable request.

Genetic analysis of colorectal carcinoma using high throughput single nucleotide polymorphism genotyping technique within the population of Jammu and Kashmir.

BACKGROUND: SNP genotyping has become increasingly more common place to understand the genetic basis of complex diseases like cancer. SNP-genotyping through MassARRAY™ is a cost-effective method to quantitatively analyse the variation of gene expression in multiple samples, making it a potential tool to identify the underlying causes of colorectal carcinogenesis. METHODS: In the present study, SNP genotyping was carried out using Agena MassARRAY™, which is a cost-effective, robust, and sensitive method to analyse multiple SNPs simultaneously. We analysed 7 genes in 492 samples (100 cases and 392 controls) associated with CRC within the population of Jammu and Kashmir. These SNPs were selected based on their association with multiple cancers in literature. RESULTS: This is the first study to explore these SNPs with colorectal cancer within the J&K population.7 SNPs with a call rate of 90% were selected for the study. Out of these, five SNPs rs2234593, rs1799966, rs2229080, rs8034191, rs1042522 were found to be significantly associated with the current study under the allelic model with an Odds Ratio OR = 2.981(1.731-5.136 at 95% CI); p value = 4.81E-05 for rs2234593,OR = 1.685(1.073-2.647 at 95% CI);; p value = 0.02292 for rs1799966, OR = 1.5 (1.1-2.3 at 95% CI), p value = 0.02 for rs2229080, OR = 1.699(1.035-2.791 at 95% CI); p value = 0.03521 for rs8034191, OR = 20.07 (11.26-35.75); p value = 1.84E-34 for rs1042522 respectively. CONCLUSION: This is the first study to find the relation of Genetic variants with the colorectal cancer within the studied population using high throughput MassARRAY™ technology. It is further anticipated that the variants should be evaluated in other population groups that may aid in understanding the genetic complexity and bridge the missing heritability.

Genetic evaluation of the variants using MassARRAY in non-small cell lung cancer among North Indians.

Lung cancer is genetically diverse and a major health burden. Non-small cell lung cancer (NSCLC) accounts for 80% of total lung cancer cases and 20% cases are Small cell lung cancer (SCLC). The present case-control association study focused on the cost effective high throughput genotyping using Agena MassARRAY matrix-assisted laser desorption/ionization-time of flight, mass spectrometry (MALDI-TOF) platform to analyze the genetic association of candidate genetic variants. We performed multiplex PCR and genotyped twelve single nucleotide polymorphisms (SNPs) in 723 samples (162 NSCLC cases and 592 healthy controls). These genetic variants were selected from literature for their association with various cancers worldwide and this is the first study from the region to examine these critically important genetic variants. With prospective case-control association study design, twelve variants from ten genes were evaluated. Amongst these six variants, TCF21 (rs12190287), ERCC1 (rs2298881, 11615), ERCC5 (rs751402), ARNTL (rs4757151), BRIP1 (rs4986764) showed significant association with NSCLC risk (p ≤ 0.003) in Jammu and Kashmir population. In-silico findings of these genetic variants showed remarkable functional roles that needs in-vitro validations. It is further anticipated that such case control studies will help us in understanding the missing heritability of non-small cell lung cancer.

Evaluation of 17 genetic variants in association with leukemia in the north Indian population using MassARRAY Sequenom.

Leukemia is a heterogeneous disorder, characterized by elevated proliferation of white blood cells. In this study, we explored the association of 17 genetic variants with leukemia patients in the Jammu and Kashmir region of north India. The variants were genotyped by using a high-throughput Agena MassARRAY platform in 758 individuals (166 cases and 592 controls). Of the 17 single-nucleotide polymorphisms (SNPs) studied, five SNPs were showing significant association with the high risk of leukemia in the north Indian population, which includes rs10069690 of telomere reverse transcriptase (TERT) with OR = 0.34 (95% CI, 0.20-0.58; p = .0008), rs2972392 (​​​PSCA) with OR 1.86 (95% CI, 1.04-3.81; p = .035), rs4986764 (BRIP1) with OR 1.34 (95% CI, 1.00-1.80; p = .04), rs6990097 (TNKS) with OR 1.81 (95% CI, 1.2-2.6; p = .001) and rs12190287 (TCF21) with OR 2.87 (95% CI, 1.72-4.7; p = .0001) by allelic association using Plink and analyzed by SPSS. This is the first study to explore these variants with leukemia in the studied population.

Evaluation of newly identified Ikaros family zinc finger 1 loci in colorectal cancer.

AIM: In this study, we evaluated the association of rs6964823 of the Ikaros Family Zinc Finger 1 (IKZF1) gene with the risk of colorectal cancer (CRC) within the population of Jammu and Kashmir (J and K). MATERIALS AND METHODS: The variant rs6964823 of the IKZF1 gene was genotyped using the TaqMan allele discrimination assay for 578 individuals (182 CRC cases and 396 healthy controls). The association of single-nucleotide polymorphisms with the disease was evaluated using logistic regression. RESULTS: It was observed that the variant rs6964823 (IKZF1) showed a significant association with an adjusted allelic odds ratio (OR) of 1.74 (1.34-2.27) at 95% confidence interval (CI), P ≤ 0.05. The dominant model (AA + AG vs. GG) was also applied, where the adjusted OR was 3.096 (2.011-4.76) at 95% CI, P > 0.05. CONCLUSIONS: It was found that the variant rs6964823 of the IKZF1 gene is associated with a higher risk of CRC within the population of J and K.

Polymorphism in the TP63 gene imparts a potential risk for leukemia in the North Indian population.

BACKGROUND: The role of single nucleotide polymorphism rs10937405 (C>T) of the TP63 gene in cancer including leukemia has previously been studied in different world populations; however, the role of this variant in leukemia in the North Indian population of Jammu and Kashmir is still unknown. OBJECTIVES: In the present study, we investigated the association of genetic variant rs10937405 with leukemic in the Jammu and Kashmir population. METHODS: A total of 588 subjects, (188 cases and 400 controls) were recruited for the study. The rs10937405 variant was genotyped by using the real-time based TaqMan assay. RESULTS: A statistically significant association was observed between the rs10937405 and leukemia [OR of 1.94 (95% CI 1.51-2.48), p=1.2x10-6]. CONCLUSION: The current study concludes that the rs10937405 variant is a risk factor for the development of leukemia in the population of Jammu and Kashmir, North India. However, it would be interesting to explore the contribution of this variant in other cancers as well. Our findings will help in the development of diagnostic markers for leukemia in the studied population and potentially for other North Indian populations.

MassArray analysis of genomic susceptibility variants in ovarian cancer.

Ovarian cancer (OC), a multifaceted and genetically heterogeneous malignancy is one of the most common cancers among women. The aim of the study is to unravel the genetic factors associated with OC and the extent of genetic heterogeneity in the populations of Jammu and Kashmir (J&K).Using the high throughput Agena MassARRAY platform, present case control study was designed which comprises 200 histopathological confirmed OC patients and 400 age and ethnicity matched healthy controls to ascertain the association of previously reported eleven single nucleotide polymorphisms (SNPs) spread over ten genes (DNMT3A, PIK3CA, FGFR2, GSTP1, ERCC5, AKT1, CASC16, CYP19A1, BCL2 and ERCC1) within the OC population of Jammu and Kashmir, India. The association of each variant was estimated using logistic regression analyses. Out of the 11 SNPs the odds ratio observed for three SNPs; rs2699887 was (1.72 at 95% CI: 1.19-2.48, p = 0.004), rs1695 was (1.87 at 95% CI: 1.28-2.71, p = 0.001), and rs2298881 was (0.66 at 95% CI: 0.46-0.96, p = 0.03) were found significantly associated with the OC after correction with confounding factors i.e. age & BMI. Furthermore, the estimation of interactive analyses was performed and odds ratio observed was 2.44 (1.72-3.47), p value < 0. 001 suggests that there was a strong existence of interplay between the selected genetic variants in OC, which demonstrate that interactive analysis highlights the role of gene-gene interaction that provides an insight among multiple little effects of various polymorphisms in OC.

Genetic variant rs2494938 of LRFN2 gene is associated with non-small cell lung cancer risk in North-Indian population.

Various Genome-wide association studies (GWAS) have reported the association of variant rs2494938 with lung cancer. However, genetic association of LRFN2 genetic variation with non-small cell lung cancer (NSCLC) in North Indian population remained unexplored. We conducted a case-control association study using TaqMan-based chemistry in which a total of 619 individuals, 189 NSCLC cases and 430 controls, were genotyped to explore the association of rs2494938 genetic variant of the LRFN2 gene with NSCLC patients from North India. The allele 'G' (risk allele) of the genetic variant rs2494938 was significantly associated with the NSCLC [OR = 1.51 (1.18-1.93 at 95% CI); p value = 0.0009]. Genetic association was also explored by applying different genetic models (Dominant, Additive). These results suggest that rs2494938 polymorphism of the LRFN2 gene is a risk factor in the North Indian populations to develop NSCLC. The LD (Linkage Disequilibrium) plot demonstrates the variant and its LD SNPs (r 2 > 0.8) and the variant has direct regulatory effect, which could affect the overall physiology of the gene. These findings could be used as diagnostic and prognostic markers in clinical studies of lung cancer patients in North Indian population groups. The present study also provides an important evidence on the genetic etiology of NSCLC in North Indian populations and further expounds GWAS findings on the role of LRFN2 in lung cancer risk. This study provides the holistic view about the non-small cell lung cancer in Jammu and Kashmir, North Indian population and it can be a hallmark of cancer if verified on a very large sample size (cohort).

MassARRAY-based single nucleotide polymorphism analysis in breast cancer of north Indian population.

BACKGROUND: Breast Cancer (BC) is associated with inherited gene mutations. High throughput genotyping of BC samples has led to the identification and characterization of biomarkers for the diagnosis of BC. The most common genetic variants studied are SNPs (Single Nucleotide Polymorphisms) that determine susceptibility to an array of diseases thus serving as a potential tool for identifying the underlying causes of breast carcinogenesis. METHODS: SNP genotyping employing the Agena MassARRAY offers a robust, sensitive, cost-effective method to assess multiple SNPs and samples simultaneously. In this present study, we analyzed 15 SNPs of 14 genes in 550 samples (150 cases and 400 controls). We identified four SNPs of genes TCF21, SLC19A1, DCC, and ERCC1 showing significant association with BC in the population under study. RESULTS: The SNPs were rs12190287 (TCF21) having OR 1.713 (1.08-2.716 at 95% CI) p-value 0.022 (dominant), rs1051266 (SLC19A1) having OR 3.461 (2.136-5.609 at 95% CI) p-value 0.000000466 (dominant), rs2229080 (DCC) having OR 0.6867 (0.5123-0.9205 at 95% CI) p-value 0.0116 (allelic) and rs2298881 (ERCC1) having OR 0.669 (0.46-0.973 at 95% CI), p-value 0.035 (additive) respectively. The in-silico analysis was further used to fortify the above findings. CONCLUSION: It is further anticipated that the variants should be evaluated in other population groups that may aid in understanding the genetic complexity and bridge the missing heritability.

MassARRAY analysis of twelve cancer related SNPs in esophageal squamous cell carcinoma in J&K, India.

BACKGROUND: MassARRAY (Agena Bioscience™) combines competitive PCR with MALDI-TOF mass spectrometry (MS) analysis that gives highly accurate, sensitive, and high-throughput methods for the quantitative analysis of variation of gene expression in multiple samples. SNPs (Single Nucleotide Polymorphisms) have a very high potential of discovering disease-gene relationships. SNP-genotyping through MassARRAY is not only a cost-effective genotyping method but also provides a platform to validate variants observed through a high-throughput Next-generation sequencing (NGS). METHODS: In the present study, we have incorporated the use of matrix-assisted laser desorption/ionization-time of flight, mass spectrometry (MALDI-TOF) as a tool for differentiating genotypes based on the mass of variant. We have performed multiplex PCR and genotyped 12 SNPs in 758 samples (166 cases and 592 controls). The 12 studied SNPs were chosen with a rationale for their association with multiple cancers in literature. RESULTS: This is the first study to explore these SNPs with esophageal cancer within the J&K population. Out of 12 SNPs, two SNPs rs12190287 of TCF21 and rs10046 of CYP19A1 were significantly associated with esophageal cancer with Odds Ratio (OR) 1.412 (1.09-1.8 at 95% CI, p = 0.008) and 1.54 (1.21-2.072 at 95% CI, p = 0.0007) within the population of Jammu and Kashmir. CONCLUSION: We explored 12 SNPs that were found to be associated with multiple cancers in literature with esophageal cancer within the population of J&K. This is the first study to find the relation of these SNPs with ESCC within the studied population. This study explores the relation of genetic and environmental factors with the ESCC susceptibility.