Exome sequencing identifies ADGRG4 G-protein-coupled receptors gene as a novel cancer biomarker in ovarian cancer patients from North India.

Adhesion G protein-coupled receptor G4 (ADGRG4) is a G protein-coupled receptor (GPCR) that belongs to the adhesion family. Participation of ADGRG4 in cell adhesion and migration, signaling pathway activation, influence on angiogenesis, and modulation of immune responses are some of the possible ways through which it may contribute to oncogenesis. Conducting extensive omics studies poses budgetary challenges to small labs in peripheral areas, primarily due to restricted research funding and resource limitations. Here we propose a low-budget model for biomarker screening. A total of 11 ovarian cancer samples were sent for exome sequencing. Among various genes, ADGRG4 variants were present in all 11 samples and thus were chosen as a potential biomarker in the present population. However, the precise role of ADGRG4 in cancer is not fully understood. The present study aims to look at the association between the ADGRG4 gene variants and their risk of ovarian cancer in the North Indian region of Jammu and Kashmir, India. Overall, 235 individuals (115 cases and 120 healthy controls) were genotyped for the selected biomarker using Sanger sequencing. Logistic regression was used to assess the relationship between the variant and ovarian cancer. A statistically significant association was identified between the ADGRG4 variant rs5930932 polymorphism and the incidence of ovarian cancer among the study population. When corrected for age and BMI, the dominating OR of variant rs5930932 was 1.035 (1.003-1.069) under HWE patients (0.95) and controls (0.18), with a p-value of (0.03). According to the findings of the current investigation, the ADGRG4 gene variant rs5930932 increases the chance of developing ovarian cancer in the studied population.

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.

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.

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.

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 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.

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.