scholarly journals Ethnic differences in allele, genotype distributions and lung cancer risk of polymorphisms of gemcitabine metabolic pathway genes in south Indian population

Author(s):  
Devika Tirumalasetty ◽  
Deepak Gopal Shewade ◽  
Biswajit Dubashi ◽  
Srinivasa Rao Katiboina

Background: Gemcitabine is a widely used cytotoxic drug in the treatment of a number of solid tumors, for instance, lung, pancreatic as well as breast cancer. As a consequence of the progressive genomic instability, the efficiency rates have eventually lowered. Genetic approach targeting one or several genes in drug targeting pathways facilitates substantially more valuable details in explaining the association between variants and also the efficacy of gemcitabine therapy. In addition, several researchers have reported ethnic discrepancies in clinical response to gemcitabine. Thus, the present study was aimed to establish the normative frequencies of genes associated with the metabolic pathway of Gemcitabine (RRM1 -37C>A (rs12806698), RRM1 -524T>C (rs11030918), CDA 79A>C (rs2072671) and CDA 435 C>T (rs1048977) in South Indian healthy population and compared with 1000 genome population. Additionally, the association of these SNPs with the risk of developing lung cancer was also evaluated.Methods: This study was carried out on 184 healthy subjects and 123 lung cancer patients of South Indian origin and genotyping was done using RT-PCR (Real Time Polymerase Chain Reaction). The frequencies of the above polymorphisms were in Hardy-Weinberg equilibrium (p >0 .05).Results: The minor allele frequencies of the SNPs RRM1 -37C>A (rs12806698), RRM1 -524T>C (rs11030918), CDA 79A>C (rs2072671) and CDA -435 C>T (rs1048977) were 31.3, 36.7, 24.5 and 22.0 respectively.Conclusions: There was a significant difference observed between the genotype and allele frequencies of south Indians with the 1000 genome populations. We also found that SNPs of RRM1 were significantly associated with lung cancer risk.

2009 ◽  
Vol 35 (8) ◽  
pp. 767-772 ◽  
Author(s):  
Helen Naemi Honma ◽  
Eduardo Mello De Capitani ◽  
Aristóteles de Souza Barbeiro ◽  
Daniel Botelho Costa ◽  
André Morcillo ◽  
...  

OBJECTIVE: To estimate and compare the frequency of CYP1A1*2A gene polymorphisms in a Brazilian population and determine the possible contribution of these genetic variations to lung cancer risk. METHODS: The study population included 200 patients with lung cancer, and the control group consisted of 264 blood donors. Genomic DNA was obtained from peripheral blood samples. The PCR-RFLP method was used for analysis of the CYP1A1*2A gene. RESULTS: There was no statistically significant difference between the lung cancer patients and the controls in terms of the distribution of CYP1A1*2A polymorphisms (p = 0.49). A multivariate logistic regression model analysis by ethnic group revealed that, within the lung cancer group, the CYP1A1*2A genotype CC plus TC was more common among the African-Brazilian patients than among the White patients (adjusted OR = 3.19; 95% CI: 1.53-6.65). CONCLUSIONS: The CYP1A1*2A gene cannot be linked with lung cancer risk in Brazilian patients at this time. Larger epidemiologic studies are needed in order to establish whether the CC plus TC polymorphism increases the risk of lung cancer in African-Brazilians.


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.


2000 ◽  
Vol 21 (1) ◽  
pp. 35-40 ◽  
Author(s):  
Monica Neri ◽  
Elio Geido ◽  
Rosangela Filiberti ◽  
Roberto Orecchia ◽  
Angela Di Vinci ◽  
...  

The glycophoryn A (GPA) assay evaluates somaticin vivomutations. It is considered a cumulative biodosimeter for genotoxic exposures and is under evaluation in cancer risk assessment.GPA, a polymorphic membrane protein of the erythrocytes, determines the MN blood groups. The N0 and NN variant frequencies (VF) may be detected in MN subjects (about 50% of the population) by flow cytometry using two differently labelled antibodies.We explored if GPA N0 and NN VF might be relevant to the assessment of individual lung cancer risk and susceptibility, in a small population with a high prevalence of heavy tobacco smokers: 8 lung cancer patients and 16 subjects with non‐malignant lung diseases associated with increased risk of lung cancer.There was a wide interindividual variability and complete overlap between non‐neoplastic and neoplastic patients. A significant positive correlation was seen with smoking duration in N0 VF (p=0.04, age‐adjusted). Current smokers (n=12) displayed higher N0 values than never (n=1) or ex‐smokers (n=11), 36.3±18.2 and 21.0±13.2, respectively (p< 0:01). No association was shown with occupational exposure.The present exploratory study suggests that assessment of individual lung cancer risk and susceptibility by the GPA assay does not seem to be feasible. The assay appears to provide a biomarker of longterm exposure to tobacco smoke.


2020 ◽  
Author(s):  
Chan Zhang ◽  
Yujing Cheng ◽  
Wanlu Chen ◽  
Qi Li ◽  
Run Dai ◽  
...  

Abstract Background: Lung cancer is the leading cause of cancer death globally. Recent studies have revealed that the CYP19A1 gene played a crucial role in cancer initiation and development. The aim of this study was to assess the association of CYP19A1 genetic polymorphisms with the risk of lung cancer in the Chinese Han population. Method: This study randomly recruited 507 lung cancer patients and 505 healthy controls. The genotypes of four SNPs of CYP19A1 gene were identified by Agena MassARRY technique. Genetic model analysis was used to assess the association between genetic variation and lung cancer risk. Odds ratio (OR) values and 95% confidence intervals (CIs) were provided for the evaluation of the lung cancer risk effect. Results: Rs28757157 and rs59429575 polymorphisms of CYP19A1 were significantly correlated with the risk of lung cancer. In stratified analysis, rs28757157 was associated with increased cancer risk in smokers and individuals aged ≤ 60 years. Meanwhile, rs59429575 was identified as a risk biomarker in females and lung adenocarcinoma patients (p < 0.05). While rs28757157 exerted a protective role among people with a BMI greater than 24 (p = 0.033). Conclusions: This study identified two new SNPs (rs28757157 and rs59429575) of CYP19A1 associated with lung cancer in Chinese Han population. These findings provide data support for further functional studies of CYP19A1 in lung cancer.


2019 ◽  
Vol 18 (2) ◽  
pp. 35-43
Author(s):  
A. N. Glushkov ◽  
E. G. Polenok ◽  
S. A. Mun ◽  
L. A. Gordeeva ◽  
M. V. Kostyanko ◽  
...  

A personalized lung cancer risk assessment is important for disease prevention.The aim of the studywas to estimate a significance of immunoanalysis of antibodies to benzo[a]pyrene, estradiol and progesterone for lung cancer risk prediction in men with respect to age and smoking.Material and methods. Serum antibodies to benzo[a]pyrene, estradiol and progesterone in the blood serum of 620 healthy men (279 smokers) and 827 lung cancer patients (627 smokers) were studied using semi-quantitative enzyme immunoassay.Results. The high lung cancer risk was observed in smokers aged over 55 years: oR=15.4 (11.5–20.8 95 % ci). the lung cancer risk in this group of patients was significantly lower when their levels of antibodies to benzo[a]pyrene and to estradiol were lower than those to progesterone: oR=3.2 (2.0–5.0). the lung cancer risk was higher when the personal levels of antibodies to benzo[a]pyrene and to estradiol were higher than the levels of antibodies to progesterone: oR=20.0 (10.5–38.1).Conclusion. The immunoassay of the blood serum antibodies specific to benzo[a]pyrene, estradiol and progesterone could be useful for determination of the lung cancer risk in men.


2020 ◽  
Author(s):  
Jiamin Wu ◽  
Yao Sun ◽  
Zichao Xiong ◽  
Fanglin Niu ◽  
Yuanwei Liu ◽  
...  

Abstract Objective: Lung cancer is the leading cause of cancer-related mortality worldwide and CMTM8 is a potential tumor suppressor gene, which is down-regulated in lung cancer. The objective of this research was to assess the association of CMTM8 genetic polymorphisms with lung cancer risk in Chinese Han population.Methods: To evaluate the correlation between CMTM8 polymorphisms and lung cancer risk, Agena MassArray platform was used for genotype determination among 509 lung cancer patients and 506 controls. Multiple genetic models, stratification analysis and haploview analysis was used by calculating odds ratio (OR) and 95% confidence intervals (CIs).Results: Significant associations were detected between CMTM8 rs6771238 and an increased lung cancer risk in codominant (adjusted OR = 1.57, 95%CI: 1.01-2.42, p = 0.044) and dominant (adjusted OR = 1.54, 95%CI: 1.01-2.36, p = 0.047)models. After gender stratification analysis,weobserved that rs6771238 was related to an increased risk of lung squamous cell carcinoma, while rs6771238 was associated with anincreased risk of lung adenocarcinoma. Rs9835916 and rs1077868 were correlated with lung cancer staging.Rs9835916 was linked to increased risk of lymph node metastasis in lung cancer patients. Conclusions: Our study firstly reported that the CMTM8 polymorphisms were a risk factors for lung cancer, which suggested the potential roles of CMTM8 in the development of lung cancerin Chinese Han population.


2021 ◽  
pp. canres.1903.2021
Author(s):  
Wei Hong ◽  
Ang Li ◽  
Yanhong Liu ◽  
Xiangjun Xiao ◽  
David C Christiani ◽  
...  

2020 ◽  
Author(s):  
Chan Zhang ◽  
Yujing Cheng ◽  
Wanlu Chen ◽  
Qi Li ◽  
Run Dai ◽  
...  

Abstract Background: Lung cancer is the leading cause of cancer death globally. Recent studies have revealed that the CYP19A1 gene played a crucial role in cancer initiation and development. The aim of this study was to assess the association of CYP19A1 genetic polymorphisms with the risk of lung cancer in the Chinese Han population.Method: This study randomly recruited 507 lung cancer patients and 505 healthy controls. The genotypes of four SNPs of CYP19A1 gene were identified by Agena MassARRY technique. Genetic model analysis was used to assess the association between genetic variation and lung cancer risk. Odds ratio (OR) values and 95% confidence intervals (CIs) were provided for the evaluation of the lung cancer risk effect.Results: Rs28757157 and rs59429575 polymorphisms of CYP19A1 were significantly correlated with the risk of lung cancer. In stratified analysis, rs28757157 was associated with increased cancer risk in smoker and individuals aged ≤60 years. Meanwhile, rs59429575 was identified as a risk biomarker in female and lung adenocarcinoma patients (p < 0.05). While rs28757157 exerted a protective role among people with a BMI greater than 24 (p = 0.033).Conclusions: This study identified two new SNPs (rs28757157 and rs59429575) of CYP19A1 associated with lung cancer in Chinese Han population. These findings provide data support for further functional studies of CYP19A1 in lung cancer.


2019 ◽  
Vol 184 (3-4) ◽  
pp. 496-499
Author(s):  
N Autsavapromporn ◽  
N Dukaew ◽  
A Wongnoppavich ◽  
B Chewaskulyong ◽  
S Roytrakul ◽  
...  

AbstractRadon is the second most important risk factor for lung cancer after tobacco smoking. In Chiang Mai, Thailand, the values of indoor radon activity concentrations are considerably higher than global average values and it is a highest level among East Asian countries. The aim of our study is to identify novel biomarkers for lung cancer risk in high radon areas using a proteomic approach. In our transitional study, a total of 81 participants of non-smokers were examined, consist of 25 lung cancer patients (LC), 16 healthy controls from low levels of natural radiation areas (LLNRA) and 40 healthy controls from high levels of natural radiation areas (HLNRA). The results showed that a total of 799 differentially expressed proteins were identified. Among these, a total of 25 proteins were observed in both LC and HLNRA, but not in LINRA. Owing to the results obtained from this study, we also point out the research direction regarding the validation of some new candidate protein as a biomarker to screen population with high risk for lung cancer in the area with high levels of radon.


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