Association of NAT-2 gene polymorphisms toward lung cancer susceptibility and prognosis in North Indian patients treated with platinum-based chemotherapy

Pharmacogenomics ◽

10.2217/pgs-2021-0080 ◽

2021 ◽

Author(s):

Harleen Kaur Walia ◽

Navneet Singh ◽

Siddharth Sharma

Keyword(s):

Lung Cancer ◽

Prognostic Factor ◽

Cancer Susceptibility ◽

Healthy Controls ◽

Slow Acetylator ◽

Mutant Genotype ◽

Platinum Based Chemotherapy ◽

Increased Risk ◽

Significant Difference ◽

Potential Prognostic Factor

Aim: The present study has been carried out to evaluate the association of the N-acetyl transferase 2 ( NAT2) variants in North Indian lung cancer patients and healthy controls. Furthermore, we have also determined the effect of the polymorphic variants of the NAT2 gene on the clinical outcomes and overall survival among lung cancer (LC) subjects treated with platinum-based doublet chemotherapy. Methods: This case-control study comprised a total of 550 cases and 550 healthy controls. The genotyping was carried out using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and the statistical analysis was carried out using MedCalc. Results: There was a lack of any significant association for both 590G>A and 803A>G polymorphisms toward risk for LC, but 857G>A polymorphism exhibited a risk toward LC (p = 0.005). Whereas, variant alleles for the 481C>T polymorphism had a decreased risk for LC (p = 0.0003). Further, 857G>A polymorphism conferred a positive association between genotype and ADCC (p = 0.001) and 481C>T polymorphism had a decreased risk for SQCC (OR = 0.39, p = 0.0006) and SCLC (p = 0.001) subjects. The smokers carrying mutant genotype for the 481C>T polymorphism had a decreased risk toward LC (p < 0.0001) even in light (p = 0.002) as well as heavy smokers (p = 0.001). In case of females, 2.59-fold and 3.66-fold increased risk of LC development was observed in subjects with intermediate and slow acetylator for the 857G>A polymorphism. Whereas, in case of males this polymorphism depicts a reduced risk for LC. On the other hand, 803A>G depicted a 2.82-fold risk of LC in case of female subjects who were slow acetylators. Our study exhibits a significant difference in the overall haplotype distribution between cases and controls. In our study overall, (857G>A, 481C>T, 803A>G) was found to be best model, but was not significant using MDR. Considering the CART results 481C>T polymorphism came out to be the most significant factor in determining the LC risk. For the 803A>G polymorphism, a threefold odds of lymph node invasion were observed for mutant genotype, the recessive model exhibited an odd of 2.8. 590G>A appears to be a potential prognostic factor for OS of SCLC patients after irinotecan therapy as the survival time for such patients was better. Conclusion: These results suggest that NAT2 variant genotype for 590G>A and 803A>G was not found to modulate risk toward LC, but 857G>A polymorphism exhibited a risk toward LC and 481C>T polymorphism had a decreased risk for LC. NAT2 590G>A appears to be a potential prognostic factor for OS of SCLC patients after irinotecan therapy and 481C>T came out to be significant factor using CART.

Download Full-text

GSTP1 Ile105Val polymorphism among North Indian lung cancer patients treated using monotherapy and poly-pharmacy

Human & Experimental Toxicology ◽

10.1177/09603271211059496 ◽

2021 ◽

pp. 096032712110594

Author(s):

Harleen Kaur Walia ◽

Navneet Singh ◽

Siddharth Sharma

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Small Cell Lung Carcinoma ◽

Predictive Biomarker ◽

Hematological Toxicity ◽

Cell Lung Carcinoma ◽

Mutant Genotype ◽

Lung Cancer Patients ◽

Platinum Based Chemotherapy ◽

Increased Risk

Background Genetic polymorphism within the P1 isoenzyme of the Glutathione-S-Transferase (GST) family is found to modulate and alter the enzyme activity of GSTP1 protein and thus may result in a change of sensitivity to platinum-based chemotherapy. We investigated the relationship between GSTP1 Ile 105 Val polymorphisms and overall survival, treatment response, and for both hematological and non-hematological toxicity of advanced North Indian lung cancer patients undergoing platinum-based double chemotherapy. Methods The polymorphism of GSTP1 Ile 105 Val in North Indian lung cancer patients was assessed by polymerase chain reaction-restriction fragment length polymorphism. A total of 682 lung cancer patients were enrolled in the study, and it was observed that patients who were carrying both the mutant alleles ( Val/Val) for the GSTP1 polymorphism showed a higher trend of median survival time (MST) as compared to the patients bearing the wild type of genotype (Ile/Ile) (MST = 8.30 vs. 7.47, p = 0.56). Based on toxicity profiling, we observed that lung cancer patients with the mutant genotype of GSTP1 (Val/Val) had an increased risk of leukopenia (OR = 2.41; 95% CI = 1.39-4.18, p = 0.001) as compared to subjects carrying both copies of the wild alleles (Ile/Ile). Our data suggested that patients with heterozygous genotype (Ile/Val) had a 2.14-fold increased risk of developing severe anemia (OR = 2.14, 95% CI = 0.97-4.62, p = 0.03). Our data also showed that in small cell lung carcinoma (SCLC) patients' polymorphism of GSTP1 was associated with thrombocytopenia (χ2 test = 7.32, p = 0.02). Conclusions Our results suggest that GSTP1 Ile105Val polymorphism could be a predictive biomarker for hematological toxicity, like leukopenia and anemia, but not thrombocytopenia or neutropenia

Download Full-text

Genetic polymorphisms in the mEH gene in relation to tobacco smoking: role in lung cancer susceptibility and survival in north Indian patients with lung cancer undergoing platinum-based chemotherapy

Future Oncology ◽

10.2217/fon-2021-0412 ◽

2021 ◽

Author(s):

Harleen Kaur Walia ◽

Navneet Singh ◽

Siddharth Sharma

Keyword(s):

Lung Cancer ◽

Epoxide Hydrolase ◽

Cancer Susceptibility ◽

Rank Test ◽

Heterozygous Genotype ◽

Log Rank Test ◽

Platinum Based Chemotherapy ◽

Potential Prognostic Factor ◽

The Relationship ◽

Lung Cancer Susceptibility

Aim: Epoxide hydrolase is involved in oxidative defenses and is responsible for the activation of carcinogens. The relationship between EPHX1 polymorphisms (Tyr113His and His139Arg) and overall survival (OS) and lung cancer (LC) risk was investigated. Methods: The study comprised 550 cases and 550 controls. Genotyping and statistical analysis were applied. Results: The variant genotypes of EPHX1 polymorphisms exhibited no association with LC risk. The Tyr113His polymorphism exhibited twofold increased odds of lymph node invasion (p = 0.04). The Tyr/His genotype is a risk factor for smokers. Subjects carrying the combined genotype for His139Arg showed better median survival time (MST) and the heterozygous genotype revealed better MST in the case of small-cell lung cancer (SCLC; 11.30 vs 6.73 months; log-rank test: p = 0.02). The heterozygous genotype (His139Arg) had longer MST in patients receiving cisplatin/carboplatin and irinotecan (11.30 vs 7.23; log-rank test: p = 0.007) Conclusion: The Tyr113His polymorphism is associated with LC risk in smokers and is a potential prognostic factor for OS in patients with SCLC after irinotecan.

Download Full-text

Evaluation of serum amyloid A, soluble E-selectin and soluble E-cadherin as lung cancer biomarkers

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20171553 ◽

2017 ◽

Vol 4 (3) ◽

pp. 650

Author(s):

Varinder Saini ◽

Chikkahonnaiah Prashanth ◽

Jasbinder Kaur ◽

Ashok Kumar Janmeja ◽

Seema Gupta ◽

...

Keyword(s):

Lung Cancer ◽

Sensitivity And Specificity ◽

Respiratory Diseases ◽

Serum Levels ◽

Screening Methods ◽

Healthy Controls ◽

Amyloid A ◽

Significant Difference ◽

Soluble E Selectin ◽

E Cadherin

Background: Lung cancer screening is a challenge. Sputum cytology, chest X-ray, low dose computed tomography and other screening methods have not proved to be very effective. Serum biomarkers are a new hope in screening of lung cancer. The present study was planned to evaluate sensitivity and specificity of serum levels of amyloid A (SAA), soluble E- selectin (sE-selectin) and soluble E-cadherin (sE-cadherin) as lung cancer biomarkers.Methods: An observational and cross-sectional study comprised of three groups with 20 subjects each of proven lung cancer cases, patients with non-malignant respiratory diseases and healthy controls. Levels of SAA, sE-selectin and sE-cadherin were measured by solid phase sandwich ELISA. Individual and collective sensitivity and specificity of these biomarkers was analysed and cut off values calculated by receiver operating curves.Results: A statistically significant difference was found in the median levels (ng/ml) of SAA in patients of lung cancer, other non-malignant respiratory diseases, and healthy controls, the levels (Mean±SD) being 24980.50±6564.14,9961.10±2000.24 and 580.95±334.94 respectively in the three groups. A sensitivity of 80% and specificity of 55% was found when SAA levels of 1068 ng/ml were taken as cut off for screening of lung cancer. However, no significant difference was found in the serum levels of sE selectin and sE cadherin between the three groups. Moreover, significant association of biomarkers could also not be established with lung cancer when they were used in combination.Conclusions: In this preliminary report from India, SAA has been found to be a promising biomarker in screening for lung cancer.

Download Full-text

Association of the CACNA2D2 gene with schizophrenia in Chinese Han population

PeerJ ◽

10.7717/peerj.8521 ◽

2020 ◽

Vol 8 ◽

pp. e8521

Author(s):

Yingli Fu ◽

Na Zhou ◽

Wei Bai ◽

Yaoyao Sun ◽

Xin Chen ◽

...

Keyword(s):

Calcium Channel ◽

Chinese Women ◽

Han Chinese ◽

Type I ◽

Genotype Distribution ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Increased Risk ◽

Significant Difference

Background Schizophrenia (SCZ) is a severely complex psychiatric disorder in which ~80% can be explained by genetic factors. Single nucleotide polymorphisms (SNPs) in calcium channel genes are potential genetic risk factors for a spectrum of psychiatric disorders including SCZ. This study evaluated the association between SNPs in the voltage-gated calcium channel auxiliary subunit alpha2delta 2 gene (CACNA2D2) and SCZ in the Han Chinese population of Northeast China. Methods A total of 761 SCZ patients and 775 healthy controls were involved in this case-control study. Three SNPs (rs3806706, rs45536634 and rs12496815) of CACNA2D2 were genotyped by the MALDI-TOF-MS technology. Genotype distribution and allele frequency differences between cases and controls were tested by Chi-square (χ2) in males and females respectively using SPSS 24.0 software. Linkage disequilibrium and haplotype analyses were conducted using Haploview4.2. The false discovery rate correction was utilized to control for Type I error by R3.2.3. Results There was a significant difference in allele frequencies (χ2 = 9.545, Padj = 0.006) and genotype distributions (χ2 = 9.275, Padj = 0.006) of rs45536634 between female SCZ patients and female healthy controls after adjusting for multiple comparisons. Minor allele A (OR = 1.871, 95% CI [1.251–2.798]) and genotype GA + AA (OR = 1.931, 95% CI [1.259–2.963]) were associated with an increased risk of SCZ. Subjects with haplotype AG consisting of rs45536634 and rs12496815 alleles had a higher risk of SCZ (OR = 1.91, 95% CI [1.26–2.90]) compared those with other haplotypes. Conclusions This study provides evidence that CACNA2D2 polymorphisms may influence the susceptibility to SCZ in Han Chinese women.

Download Full-text

How to Screen and Prevent Metabolic Syndrome in Patients of PCOS Early: Implications From Metabolomics

10.21203/rs.3.rs-158919/v1 ◽

2021 ◽

Author(s):

Xiaoxuan Zhao ◽

Xiaoling Feng ◽

Xinjie Zhao ◽

Yuepeng Jiang ◽

Xianna Li ◽

...

Keyword(s):

Metabolic Syndrome ◽

Clinical Diagnosis ◽

Polycystic Ovary ◽

Ultra Performance Liquid Chromatography ◽

Healthy Controls ◽

Metabolic Characteristics ◽

Increased Risk ◽

Significant Difference ◽

Pcos Group ◽

Reproductive Endocrine

Abstract Background: Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine disorder，with an increased risk of type 2 diabetes mellitus and cardiovascular disease, of which metabolic syndrome (MS) is an indispensable springboard to communicate PCOS and various comlications. Our aim was to study the potential metabolic characteristics of PCOS-MS, and identify sensitive biomarkers so as to provide targets for clinical screening, diagnosis and treatment.Methods: 44 PCOS patients with MS, 34 PCOS patients without MS and 32 healthy controls were studied. Plasma samples of subjects were tested by ultra performance liquid chromatography (UPLC) system combined with LTQ-orbi-trap mass spectrometry. The changes of metabolic characteristics from PCOS to PCOS-MS were systematically analyzed. Correlations between differential metabolites and clinical characteristics of PCOS-MS were assessed. Differential metabolites with high correlation were further evaluated by the receiver operating characteristic (ROC) curve to identify their sensitivity as screening indicators.Results: There were significant difference in general characteristics, reproductive hormone and metabolic parameters in PCOS-MS group when compared with PCOS group and healthy controls. We found 30 differential metabolites which were involved in 23 pathways when compared with PCOS group. The metabolic network further reflects the metabolic environment, including the interaction between metabolic pathways, modules, enzymes, reactions and metabolites.In the correlation analysis, 17 pairs of correlation coefficient between differential metabolites and clincal parameters were greater than 0.4, involving 11 metabolites that has the potential to be a marker for clinical diagnosis. They were assessed by ROC whose area under curve (AUC) were all greater than 0.7, with a good sensitivity. Furthermore, combinational metabolic biomarkers, such as glutamic acid+leucine+phenylalanine and carnitine C 4: 0+carnitine C18:1+carnitine C5:0 are expected to be sensitive combinational biomarkers in clinical practice.Conclusion: Our study provides a new insight to understand the pathogenesis mechanism, and the discriminating metabolites may help screen high-risk of MS in patients with PCOS and provide sensitive biomarkers for clinical diagnosis.

Download Full-text

Association of GWAS-Identified Lung Cancer Susceptibility Loci with Survival Length in Patients with Small-Cell Lung Cancer Treated with Platinum-Based Chemotherapy

PLoS ONE ◽

10.1371/journal.pone.0113574 ◽

2014 ◽

Vol 9 (11) ◽

pp. e113574 ◽

Cited By ~ 6

Author(s):

Dong Li ◽

Lixuan Wei ◽

Binghe Xu ◽

Dianke Yu ◽

Jiang Chang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cancer Susceptibility ◽

Small Cell ◽

Susceptibility Loci ◽

Small Cell Lung ◽

Platinum Based Chemotherapy ◽

Lung Cancer Susceptibility

Download Full-text

Potential Impact of MicroRNA-423 Gene Variability in Coronary Artery Disease

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530318666181005095724 ◽

2019 ◽

Vol 19 (1) ◽

pp. 67-74 ◽

Cited By ~ 8

Author(s):

Chandan K. Jha ◽

Rashid Mir ◽

Imadeldin Elfaki ◽

Naina Khullar ◽

Suriya Rehman ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Recessive Model ◽

Amplification Refractory Mutation System ◽

Genotype Distribution ◽

Healthy Controls ◽

Increased Risk ◽

Significant Difference ◽

Artery Disease ◽

Gene Variability

Aim: Studies have evaluated the association of miRNA-423 C>A genotyping with the susceptibility to various diseases such cancers, atherosclerosis and inflammatory bowel disease but the results were contradictory. However, no studies have reported the association between miRNA-423 rs6505162 C>A polymorphism and susceptibility of coronary artery disease. MicroRNAs regulate expression of multiple genes involved in atherogenesis. Therefore, we investigated the association of microRNA-423C>T gene variations with susceptibility to coronary artery disease. Methodology: This study was conducted on 100 coronary artery disease patients and 117 matched healthy controls. The genotyping of the microRNA-423 rs6505162C>A was performed by using Amplification refractory mutation system PCR method (ARMS-PCR). Results: A significant difference was observed in the genotype distribution among the coronary artery disease cases and sex-matched healthy controls (P=0.048). The frequencies of all three genotypes CC, CA, AA reported in the patient’s samples were 55%, 41% and 4% and in the healthy controls samples were 55%, 41% and 4% respectively. Our findings showed that the microRNA-423 C>A variant was associated with an increased risk of coronary artery disease in codominant model (OR = 1.96, 95 % CI, 1.12-3.42; RR 1.35(1.05-1.75, p=0.017) of microRNA-423CA genotype and significant association in dominant model (OR 1.97, 95% CI (1.14-3.39), (CA+AA vs CC) and non-significant association for recessive model (OR=1.42, 95%CI=0.42-4.83, P=0.56, AA vs CC+CA).While, the A allele significantly increased the risk of coronary artery disease (OR =1.56, 95 % CI, 1.03-2.37; p=0.035) compared to C allele. Therefore, it was observed that more than 1.96, 1.97 and 1.56 fold increased risk of developing coronary artery disease. Conclusion: Our findings indicated that microRNA-423 CA genotype and A allele are associated with an increased susceptibility to Coronary artery disease.

Download Full-text

Value of immune factors for monitoring risk of lung cancer in patients with interstitial lung disease

Journal of International Medical Research ◽

10.1177/0300060519847403 ◽

2019 ◽

Vol 47 (7) ◽

pp. 3344-3353

Author(s):

Ning Li ◽

Haisheng Hu ◽

Ge Wu ◽

Baoqing Sun

Keyword(s):

Lung Cancer ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Serum Levels ◽

Scaling Analysis ◽

Healthy Controls ◽

Healthy Individuals ◽

Reactive Protein ◽

Increased Risk ◽

Immune Factors

Objective Patients with interstitial lung disease (ILD) are at increased risk of developing lung cancer. We aimed to investigate the clinical significance of serum immune factors in this progression. Methods We retrospectively screened a hospital database from January 2012 to December 2016 for patients with lung cancer and ILD. We measured serum levels of C3, C4, IgA, IgG, IgM, C-reactive protein (CRP), ceruloplasmin (CER), and rheumatoid factor in these patients and in healthy controls. Results We analyzed data for 262 patients with lung cancer, 220 with ILD, and 57 healthy controls. CER levels were significantly higher in patients with lung cancer (0.35 ± 0.10 g/L) compared with both ILD patients (0.31 ± 0.25 g/L) and healthy individuals (0.25 ± 0.04 g/L). C3 and C4 levels were both significantly higher in healthy individuals compared with patients with lung cancer (C3: 1.70 ± 0.29 vs 1.04 ± 0.26 g/L, C4: 0.27 ± 0.24 vs 0.24 ± 0.09 g/L) and ILD (C3: 1.70 ± 0.29 vs 0.97 ± 0.25 g/L, C4: 0.27 ± 0.24 vs 0.21 ± 0.09 g/L). Optimal scaling analysis demonstrated that lung cancer was closely associated with CRP, CER, C3, and C4. Conclusions Increased levels of CRP and CER and decreased levels of C3 and C4 may identify patients with ILD at high risk of developing lung cancer.

Download Full-text