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

2021 ◽  
pp. 096032712110594
Author(s):  
Harleen Kaur Walia ◽  
Navneet Singh ◽  
Siddharth Sharma

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

2017 ◽  
Vol 37 (4) ◽  
pp. 288-292
Author(s):  
Jatu Aviani ◽  
Satria Maulana EH ◽  
Ita Haryatie ◽  
Farih Raharjo ◽  
Yusup Subagio Sutanto ◽  
...  

Background: Lung cancer and pulmonary tuberculosis (TB) are global health problem. Similarity of symptoms of both made misdiagnose of lung cancer as TB and treated with Anti Tuberculosis Treatment (ATT). Evaluation of ATT often inaccurate, causing late diagnosis of lung cancer. This study aimed is to determine the lung cancer percentage with delayed diagnosis due giving of ATT for >1 month. Methods: A prospective descriptive study was performed from January 2014-February 2016 in Dr. Moewardi Hospital, Surakarta taken from the patient's medical record. Results: As much 293 patients with lung cancer consisted of 188 males (64.4%) and 105 females (35.8%) with the average age was 57 years old. The types of the lung cancer were non-small cell lung carcinoma (NSCLC) consisted of adenocarcinoma 195 subjects (66.6%), squamous cell carcinoma 65 subjects (22.2%), large cell carcinoma 23 subjects (7.8%) and neuroendocrine carcinoma 4 subjects (1.4%). The stages of the NSCLC were stage I (0%), II (0%), IIIa (0%), IIIb (11.7%) and IV (88.3%). Among 293 lung cancer patients, 89 subjects (30.4%) were diagnosis as pulmonary TB. Two subjects (2.2%) of 89 subjects were truly pulmonary TB while the rest 87 subjects were not pulmonary TB and had ATT for average 12 weeks with the longest period was 16 weeks. The ATT duration >1 month was 76.4%. Conclusions: Percentage of lung cancer patients with ATT before being referred to dr. Moewardi hospital were 30.4% of 293 lung cancer patients while 68 subjects (76.4%) of whom had received ATT >1 month. (J Respir Indo. 2017; 37(4): 288-92)


2021 ◽  
Author(s):  
Yukti Choudhury ◽  
Min-Han Tan ◽  
Jun Li Shi ◽  
Augustine Tee ◽  
Kao Chin Ngeow ◽  
...  

Background: Tissue biopsy is an integral part of the diagnostic approach to lung cancer. It is however invasive and associated with limitations of tissue heterogeneity. Liquid biopsies may complement tissue testing by providing additional molecular information and may be particularly helpful in patients from whom obtaining sufficient tissue for genomic profiling is challenging. Methods: Patients with suspected lung cancer (n=71) were prospectively recruited. Blood and diagnostic tissue samples were collected within 48 hrs of each other. Plasma cell-free DNA (cfDNA) testing was done using an ultrasensitive amplicon-based next-generation sequencing (NGS) panel (plasma NGS testing). For cases diagnosed as non-small cell lung carcinoma (NSCLC) via histology or cytology, targeted testing for epidermal growth factor receptor (EGFR) mutations was performed using tissue biopsy samples, where available (tissue EGFR testing). Concordance of clinically actionable mutations between methods and sample types were assessed. Results: For confirmed NSCLC cases (n = 54), tissue EGFR test results were available only for 70.3% (38/54) due to sample inadequacies, compared to blood samples for 98.1% (53/54) cases. Tissue EGFR testing identified sensitizing EGFR (L858R or exon 19 deletion) mutation in 31.6% (12/38) of cases. Plasma NGS identified clinically actionable mutations in 37.7% (20/53) of cases, including EGFR mutations in two cases with no tissue EGFR results, and mutations in KRAS, BRAF and MET. Overall sensitivity of EGFR sensitizing mutation detection by plasma NGS was 75% (9/12), and specificity was 100% (25/25) in patients tested in both tissue EGFR and plasma NGS (n=37). In this cohort of patients, tissue EGFR testing alone informed clinical decisions in 22.2% (12/54) of cases. Adding plasma NGS to tissue EGFR testing increased the detection rate of actionable mutations to 42.6% (23/54), representing a near doubling (1.9-fold increase) of clinically relevant findings. The average turnaround time (TAT) of plasma NGS was shorter than standard tissue testing (10 days vs. 29.9 days, p-value <0.05). Conclusions: In the first-line setting, plasma NGS was highly concordant with tissue EGFR testing. Plasma NGS increases the detection of actionable findings with shorter time to results. This study outlines the clinical utility of a complementary plasma mutation profiling in the routine management of lung cancer patients.


2019 ◽  
Vol 166 (4) ◽  
pp. 323-329 ◽  
Author(s):  
Randa H Mohamed ◽  
Heba F Pasha ◽  
Doaa M Gad ◽  
Mostafa M Toam

AbstractRecently, MicroRNAs polymorphisms and their serum expression have been linked to increase risk of various cancers. The aim of this study was to elucidate the association between single nucleotide polymorphisms of miR-146a and miR-196a-2 and their serum expression and lung cancer risk. One hundred and twenty lung cancer patients and 120 health controls were included in this study. Genotyping and expression for miR-146a and miR-196a-2 were performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and quantitative real-time PCR. Individuals carrying miR-146a CG and CC genotypes had significantly increased risk for lung cancer than those carrying miR-146a GG genotype. MiR-146a expression significantly decreased in miR-146a CG and CC genotypes carriers as compared with GG genotype carriers. MiR-196a-2 CT and TT genotypes were significantly associated with increased lung cancer while the highest expression of MiR-196a-2 was detected in miR-196a-2 CC genotype carriers. Serum miR-146a was significantly decreased in lung cancer patients while serum miR-196a-2 expression was significantly increased in lung cancer patients. In conclusion, miR-146a and miR-196a-2 genes polymorphisms and their circulating levels were associated with lung cancer risk in Egyptians and may be helpful in early detection of lung cancer.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dawei Zhu ◽  
Ruoxi Ding ◽  
Yong Ma ◽  
Zhishui Chen ◽  
Xuefeng Shi ◽  
...  

Abstract Background Comorbidity has been established as one of the important predictors of poor prognosis in lung cancer. In this study, we analyzed the prevalence of main comorbidities and its association with hospital readmission and fatality for lung cancer patients in China. Methods The analyses are based on China Urban Employees’ Basic Medical insurance (UEBMI) and Urban Residents’ Basic Medical Insurance (URBMI) claims database and Hospital Information System (HIS) Database in the Beijing University Cancer Hospital in 2013–2016. We use Elixhauser Comorbidity Index to identify main types of comorbidities. Results Among 10,175 lung cancer patients, 32.2% had at least one comorbid condition, and the proportion of patients with one, two, and three or more comorbidities was 21.7, 8.3 and 2.2%, respectively. The most prevalent comorbidities identified were other malignancy (7.5%), hypertension (5.4%), pulmonary disease (3.7%), diabetes mellitus (2.5%), cardiovascular disease (2.4%) and liver disease (2.3%). The predicted probability of having comorbidity and the predicted number of comorbidities was higher for middle elderly age groups, and then decreased among patients older than 85 years. Comorbidity was positively associated with increased risk of 31-days readmission and in-hospital death. Conclusion Our study is the first to provide an overview of comorbidity among lung cancer patients in China, underlines the necessity of incorporating comorbidity in the design of screening, treatment and management of lung cancer patients in China.


2021 ◽  
Author(s):  
Harleen Kaur Walia ◽  
Navneet Singh ◽  
Siddharth Sharma

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.


Sign in / Sign up

Export Citation Format

Share Document