scholarly journals Genetic variants of SULT1A1 and XRCC1 genes and risk of lung cancer in Bangladeshi population

Tumor Biology ◽  
2017 ◽  
Vol 39 (11) ◽  
pp. 101042831772927 ◽  
Author(s):  
Tasnova Tasnim ◽  
Mir Md Abdullah Al-Mamun ◽  
Noor Ahmed Nahid ◽  
Md Reazul Islam ◽  
Mohd Nazmul Hasan Apu ◽  
...  

Lung cancer is one of the most frequently occurring cancers throughout the world as well as in Bangladesh. This study aimed to correlate the prognostic and/or predictive value of functional polymorphisms in SULT1A1 (rs9282861) and XRCC1 (rs25487) genes and lung cancer risk in Bangladeshi population. A case-control study was conducted which comprises 202 lung cancer patients and 242 healthy volunteers taking into account the age, sex, and smoking status. After isolation of genomic DNA, genotyping was done by polymerase chain reaction–restriction fragment length polymorphism method and the lung cancer risk was evaluated as odds ratio that was adjusted for age, sex, and smoking status. A significant association was found between SULT1A1 rs9282861 and XRCC1 rs25487 polymorphisms and lung cancer risk. In case of rs9282861 polymorphism, Arg/His (adjusted odds ratio = 5.06, 95% confidence interval = 3.05–8.41, p < 0.05) and His/His (adjusted odds ratio = 3.88, 95% confidence interval = 2.20–6.82, p < 0.05) genotypes were strongly associated with increased risk of lung cancer in comparison to the Arg/Arg genotype. In case of rs25487 polymorphism, Arg/Gln heterozygote (adjusted odds ratio = 4.57, 95% confidence interval = 2.79–7.46, p < 0.05) and Gln/Gln mutant homozygote (adjusted odds ratio = 4.99, 95% confidence interval = 2.66–9.36, p < 0.05) were also found to be significantly associated with increased risk of lung cancer. This study demonstrates that the presence of His allele and Gln allele in case of SULT1A1 rs9282861 and XRCC1 rs25487, respectively, involve in lung cancer prognosis in Bangladeshi population.

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Rui Niu ◽  
Yuzhuo Wang ◽  
Meng Zhu ◽  
Yifan Wen ◽  
Jie Sun ◽  
...  

POU5F1 is a key regulator of self-renewal and differentiation in embryonic stem cells and may be associated with initiation, promotion, and progression in cancer. We hypothesized that functional polymorphisms inPOU5F1may play an important role in modifying the lung cancer risk. To test this hypothesis, we conducted a case-control study to explore the association between 17 potentially functional SNPs inPOU5F1gene and the lung cancer risk in 1,341 incident lung cancer cases and 1,982 healthy controls in a Chinese population. We found that variant alleles of rs887468 and rs3130457 were significantly associated with increased risk of lung cancer after multiple comparison (OR = 1.29, 95% CI: 1.11–1.51,Pfdr=0.017for rs887468; OR = 1.29, 95% CI: 1.10–1.51,Pfdr=0.034for rs3130457, resp.). In addition, we detected a significant interaction between rs887468 genotypes and smoking status on lung cancer risk (P=0.017). Combined analysis of these 2 SNPs showed a significant allele-dosage association between the number of risk alleles and increased risk of lung cancer (Ptrend<0.001). These findings indicate that potentially functional polymorphisms inPOU5F1gene may contribute to lung cancer susceptibility in a Chinese population.


Tumor Biology ◽  
2019 ◽  
Vol 41 (3) ◽  
pp. 101042831983083 ◽  
Author(s):  
Hasnain Imtiaz ◽  
Sharmin Afroz ◽  
Md Amir Hossain ◽  
Sm Faysal Bellah ◽  
Md Mostafizur Rahman ◽  
...  

The polymorphisms of invasion suppressor gene CDH1 and DNA mismatch repair gene Exo1 have been reported to play critical role in the development, tumorigenesis, and progression of several kinds of cancers including prostate cancer. This study was designed to analyze the contribution of single-nucleotide polymorphisms of the CDH1 (-160C/A) and Exo1 (K589E) to prostate cancer susceptibility in Bangladeshi population. The study included 100 prostate cancer cases and age-matched 100 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to determine the genetic polymorphisms. A significant association was found between CDH1 -160C/A (rs16260) and Exo1 (rs1047840, K589E) polymorphisms and prostate cancer risk. In case of CDH1 -160C/A polymorphism, the frequencies of the three genotypes C/C,C/A, and A/A were 45%, 48%, and 7% in cases and 63%, 32%, and 5% in controls, respectively. The heterozygote C/A genotype and combined C/A + A/A genotypes showed 2.10-fold (odds ratio = 2.1000, 95% confidence interval = 1.2956–4.0905, p = 0.013) and 2.08-fold (odds ratio = 2.0811, 95% confidence interval = 1.1820–3.6641, p = 0.011) increased risk of prostate cancer, respectively, when compared with homozygous C/C genotypes. The variant A allele also was associated with increased risk of prostate cancer (odds ratio = 1.6901, 95% confidence interval = 1.0740–2.6597, p = 0.0233). In case of Exo1 (K589E) polymorphism, G/A heterozygote, A/A homozygote, and combined G/A + A/A genotypes were found to be associated with 2.30-, 4.85-, and 3.04-fold higher risk of prostate cancer, respectively (odds ratio = 2.3021, 95% confidence interval = 2.956–4.0905, p = 0.0031; odds ratio = 4.8462, 95% confidence interval = 1.0198–23.0284, p = 0.0291; OR = 3.0362, 95% confidence interval = 1.7054–5.4053, p = 0.0001, respectively). The “A” allele showed significant association with increased susceptibility (2.29-fold) to prostate cancer (odds ratio = 2.2955, 95% confidence interval = 1.4529–3.6270, p = 0.0004). Our results suggest that CDH1 -160C/A and Exo1 K589E polymorphisms are associated with increased susceptibility to prostate cancer in Bangladeshi population.


2021 ◽  
Author(s):  
Naisi Zhao ◽  
Mengyuan Ruan ◽  
Devin C. Koestler ◽  
Jiayun Lu ◽  
Karl T. Kelsey ◽  
...  

Background Examining inflammation-related DNA methylation alterations in blood could help elucidate the role of inflammation in lung cancer etiology and aid discovery of factors that are key to lung cancer development and progression. In a nested case-control study, we estimated the neutrophil-to-lymphocyte ratio using a validated index, methylation-derived NLR (mdNLR), and quantified DNA methylation levels at loci previously linked with circulating concentrations of C-reactive protein (CRP). We examined associations between these measures and lung cancer risk, and among the cases, lung cancer survival, using pre-diagnostic blood samples of cases (median of 14 years before diagnosis) and controls in the CLUE I/II cohorts. Our analyses controlled for self-reported smoking and methylation-predicted cumulative smoking in order to better focus our examinations on the DNA methylation marks that are informative of the immune response profile. Results Using conditional logistic regression and further adjusting for BMI, batch effects, and a smoking-based methylation score, we observed a 47% increased risk of non-small cell lung cancer (NSCLC) for one standard deviation increase in mdNLR (n = 150 pairs; OR: 1.47 [1.08, 2.02]) and found the estimated CRP Scores to be inversely associated with risk of NSCLC risk after additionally adjusting for methylation-predicted pack-years (n = 150 pairs; Score 1 OR: 0.57 [0.40, 0.81]; Score 2 OR: 0.62 [0.45, 0.84]; Score 3 OR: 0.65 [0.44, 0.95]). Using Cox proportional-hazards models and adjusting age, sex, smoking status, methylation-predicted pack-years, BMI, batch effect, and stage, we observed a 27% increased risk of dying from lung cancer for one standard deviation increase in mdNLR (n = 145 deaths in 205 cases; HR: 1.27 [1.08, 1.50]). A 50% increased risk of dying from lung cancer for one standard deviation increase in mdNLR was observed for NSCLC cases (n = 103 deaths in 149 cases; HR: 1.50 [1.19, 1.89]). Conclusions A better understanding of inflammation-associated methylation-based biomarkers in lung cancer development could provide insight into critical pathways that may help identify new markers of early disease and survival.


Tumor Biology ◽  
2020 ◽  
Vol 42 (9) ◽  
pp. 101042832095895
Author(s):  
Priyanka Florina Karmokar ◽  
Samia Shabnaz ◽  
Md. Abdul Aziz ◽  
Md. Asaduzzaman ◽  
Mohammad Shahriar ◽  
...  

Colorectal cancer is the fourth most common type of malignancy worldwide that may develop due to the accumulation of several genetic variations. Different single nucleotide polymorphisms of SMAD1 gene are assumed to be linked with increased colorectal cancer risk. The current case-control study was conducted to verify the association of genetic polymorphisms of SMAD1 (rs11100883 and rs7661162) with colorectal cancer in the Bangladeshi population. This study was performed on 275 colorectal cancer patients and 300 healthy volunteers using polymerase chain reaction–restriction fragment length polymorphism method. The odds ratios were adjusted for age and sex with logistic regression analysis. In case of SMAD1 rs11100883 polymorphism, GA heterozygous genotype, GA + AA (dominant model), and minor allele “A” were significantly associated with colorectal cancer (adjusted odds ratio = 1.55, 95% confidence interval = 1.09–2.20, p = 0.014; adjusted odds ratio = 1.59, 95% confidence interval = 1.13–2.23, p = 0.008; and odds ratio = 1.35, 95% confidence interval = 1.06–1.73, p = 0.015, respectively) and the significance exists after the Bonferroni correction. Again, single nucleotide polymorphism rs7661162 showed significant association with an elevated colorectal cancer risk for AG heterozygous genotype, AG + GG (dominant model), AG versus AA + GG (overdominant model), and minor allele “G” (adjusted odds ratio = 1.78, 95% confidence interval = 1.24–2.56, p = 0.002; adjusted odds ratio = 1.68, 95% confidence interval = 1.18–2.39, p = 0.004; adjusted odds ratio = 1.76, 95% confidence interval = 1.23–2.53, p = 0.002; and odds ratio = 1.47, 95% confidence interval = 1.08–2.00, p = 0.014, respectively) and significance withstands after the Bonferroni correction. No significant age and gender differences between cases and controls were observed. In silico, gene expression analysis showed that the SMAD1 mRNA level was downregulated in the colon and rectal cancer tissues compared to healthy tissues. In conclusion, our findings indicate that SMAD1 rs11100883 and rs7661162 polymorphisms are responsible for increasing the susceptibility of colorectal cancer development in the Bangladeshi population.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ke Zhu ◽  
Aiqun Xu ◽  
Wanli Xia ◽  
Pulin Li ◽  
Binbin Zhang ◽  
...  

Lung cancer is the leading cause of cancer-related death worldwide and has a high incidence rate. N-Acetyltransferase 2 (NAT2) is a polymorphic xenobiotic enzyme, which can catalyze N-acetylation and O-acetylation of various carcinogens such as aromatic, heterocyclic amines and hydrazines. At present, many studies have explored the effects of NAT2 polymorphism on lung cancer, but we found inconsistent results. We researched 18 published studies, involving 4,016 patients and 5,469 controls, to more accurately assess the effects of NAT2 polymorphism on lung cancer risk and to investigate whether smoking is associated. We used STATA software to analyze the extracted data and used STATA for subgroup analysis, sensitivity analysis, and to perform publication bias tests. To determine the correlation, we used the crude odds ratio (ORs) with 95% confidence interval (CIs). Our study was prospectively registered in PROSPERO (CRD42020159737). The odds ratio was 1.53 (95% CI: 1.21–1.95, I² = 45.2%, P=0.104) for the NAT2 slow + intermediate phenotype versus rapid phenotype. The results suggested that people with NAT2 non-rapid (slow + intermediate) phenotype have a significantly increased risk of lung cancer. In addition, NAT2 rapid phenotype was significantly associated with reduced risk of lung cancer, compared with slow phenotype or intermediate phenotype (slow phenotype vs. rapid phenotype: OR: 1.61, 95% CI: 1.07–2.42, I²= 50%, P= 0.075; intermediate phenotype vs. rapid phenotype: OR: 1.47, 95% CI: 1.15–1.88, I²= 40.3%, P= 0.137).


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Naisi Zhao ◽  
Mengyuan Ruan ◽  
Devin C. Koestler ◽  
Jiayun Lu ◽  
Lucas A. Salas ◽  
...  

Abstract Background Examining immunity-related DNA methylation alterations in blood could help elucidate the role of the immune response in lung cancer etiology and aid in discovering factors that are key to lung cancer development and progression. In a nested, matched case–control study, we estimated methylation-derived NLR (mdNLR) and quantified DNA methylation levels at loci previously linked with circulating concentrations of C-reactive protein (CRP). We examined associations between these measures and lung cancer risk and survival. Results Using conditional logistic regression and further adjusting for BMI, batch effects, and a smoking-based methylation score, we observed a 47% increased risk of non-small cell lung cancer (NSCLC) for one standard deviation (SD) increase in mdNLR (n = 150 pairs; OR: 1.47, 95% CI 1.08, 2.02). Using a similar model, the estimated CRP Scores were inversely associated with risk of NSCLC (e.g., Score 1 OR: 0.57, 95% CI: 0.40, 0.81). Using Cox proportional hazards models adjusting for age, sex, smoking status, methylation-predicted pack-years, BMI, batch effect, and stage, we observed a 28% increased risk of dying from lung cancer (n = 145 deaths in 205 cases; HR: 1.28, 95% CI: 1.09, 1.50) for one SD increase in mdNLR. Conclusions Our study demonstrates that immunity status measured with DNA methylation markers is associated with lung cancer a decade or more prior to cancer diagnosis. A better understanding of immunity-associated methylation-based biomarkers in lung cancer development could provide insight into critical pathways.


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.


2013 ◽  
Vol 416 ◽  
pp. 11-19 ◽  
Author(s):  
Mohammad Safiqul Islam ◽  
Maizbha Uddin Ahmed ◽  
Muhammad Shahdaat Bin Sayeed ◽  
Abdullah Al Maruf ◽  
A.G.M. Mostofa ◽  
...  

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.


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