scholarly journals Methylation-derived inflammatory measures and lung cancer risk and survival

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Naisi Zhao ◽  
Mengyuan Ruan ◽  
Devin C. Koestler ◽  
Jiayun Lu ◽  
Lucas A. Salas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Cancer Risk ◽  
Lung Cancer Risk ◽  
Smoking Status ◽  
Conditional Logistic Regression ◽  
Cox Proportional Hazards ◽  
Cancer Development ◽  
Cancer Etiology ◽  
Increased Risk

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.

scholarly journals Methylation-derived Inflammatory Measures and Lung Cancer Risk and Survival

2021 ◽  
Author(s):  
Naisi Zhao ◽  
Mengyuan Ruan ◽  
Devin C. Koestler ◽  
Jiayun Lu ◽  
Karl T. Kelsey ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Standard Deviation ◽  
Cancer Risk ◽  
Lung Cancer Risk ◽  
Smoking Status ◽  
Conditional Logistic Regression ◽  
Cancer Development ◽  
Standard Deviation Increase ◽  
Increased Risk

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.

scholarly journals Potentially Functional Polymorphisms inPOU5F1Gene Are Associated with the Risk of Lung Cancer in Han Chinese

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Rui Niu ◽  
Yuzhuo Wang ◽  
Meng Zhu ◽  
Yifan Wen ◽  
Jie Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Chinese Population ◽  
Lung Cancer Risk ◽  
Cancer Susceptibility ◽  
Smoking Status ◽  
Embryonic Stem ◽  
Functional Polymorphisms ◽  
Allele Dosage ◽  
Increased Risk

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.

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 ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Lung Cancer Risk ◽  
Smoking Status ◽  
Functional Polymorphisms ◽  
Increased Risk ◽  
Bangladeshi Population

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.

scholarly journals AHRR methylation in heavy smokers: associations with smoking, lung cancer risk, and lung cancer mortality

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Laurie Grieshober ◽  
Stefan Graw ◽  
Matt J. Barnett ◽  
Mark D. Thornquist ◽  
Gary E. Goodman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Screening ◽  
Cancer Risk ◽  
Lung Cancer Risk ◽  
Conditional Logistic Regression ◽  
Asbestos Exposure ◽  
Lung Cancer Screening ◽  
Cox Proportional Hazards ◽  
Small Cell ◽  
Heavy Smokers

Abstract Background A low level of methylation at cg05575921 in the aryl-hydrocarbon receptor repressor (AHRR) gene is robustly associated with smoking, and some studies have observed associations between cg05575921 methylation and increased lung cancer risk and mortality. To prospectively examine whether decreased methylation at cg05575921 may identify high risk subpopulations for lung cancer screening among heavy smokers, and mortality in cases, we evaluated associations between cg05575921 methylation and lung cancer risk and mortality, by histotype, in heavy smokers. Methods The β-Carotene and Retinol Efficacy Trial (CARET) included enrollees ages 45–69 with ≥ 20 pack-year smoking histories and/or occupational asbestos exposure. A subset of CARET participants had cg05575921 methylation available from HumanMethylationEPIC assays of blood collected on average 4.3 years prior to lung cancer diagnosis in cases. Cg05575921 methylation β-values were treated continuously for a 10% methylation decrease and as quintiles, where quintile 1 (Q1, referent) represents high methylation and Q5, low methylation. We used conditional logistic regression models to examine lung cancer risk overall and by histotype in a nested case-control study including 316 lung cancer cases (diagnosed through 2005) and 316 lung cancer-free controls matched on age (±5 years), sex, race/ethnicity, enrollment year, current/former smoking, asbestos exposure, and follow-up time. Mortality analyses included 372 lung cancer cases diagnosed between 1985 and 2013 with available methylation data. We used Cox proportional hazards models to examine mortality overall and by histotype. Results Decreased cg05575921 methylation was strongly associated with smoking, even in our population of heavy smokers. We did not observe associations between decreased pre-diagnosis cg05575921 methylation and increased lung cancer risk, overall or by histotype. We observed linear increasing trends for lung cancer-specific mortality across decreasing cg05575921 methylation quintiles for adenocarcinoma and small cell carcinoma (P-trends = 0.01 and 0.04, respectively). Conclusions In our study of heavy smokers, decreased cg05575921 methylation was strongly associated with smoking but not increased lung cancer risk. The observed association between cg05575921 methylation and increased mortality in adenocarcinoma and small cell histotypes requires further examination. Our results do not support using decreased cg05575921 methylation as a biomarker for lung cancer screening risk stratification.

miR-146a and miR-196a-2 genes polymorphisms and its circulating levels in lung cancer patients

2019 ◽  
Vol 166 (4) ◽  
pp. 323-329 ◽  
Author(s):  
Randa H Mohamed ◽  
Heba F Pasha ◽  
Doaa M Gad ◽  
Mostafa M Toam
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Cancer Patients ◽  
Lung Cancer Risk ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Lung Cancer Patients ◽  
Increased Risk ◽  
Increase Risk ◽  
Circulating Levels

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.

scholarly journals Analysis of Erythrocyte Glycophorin-A Variants by Flow Cytometry in Lung Disease Patients Detects the Effect of Tobacco Smoke

2000 ◽  
Vol 21 (1) ◽  
pp. 35-40 ◽  
Author(s):  
Monica Neri ◽  
Elio Geido ◽  
Rosangela Filiberti ◽  
Roberto Orecchia ◽  
Angela Di Vinci ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Flow Cytometry ◽  
Cancer Risk ◽  
Tobacco Smoke ◽  
Lung Cancer Risk ◽  
Small Population ◽  
Cancer Risk Assessment ◽  
Lung Cancer Patients ◽  
Increased Risk

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.

Domestic incense use and lung cancer in Asia: a review

2016 ◽  
Vol 31 (1) ◽  
Author(s):  
Wei Jie Seow ◽  
Qing Lan
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Air Pollution ◽  
Cancer Risk ◽  
Lung Cancer Risk ◽  
Smoking Status ◽  
Case Control ◽  
Negative Association ◽  
Future Studies ◽  
Manual Review

AbstractWhile there is strong evidence for the association between household air pollution and lung cancer among non-smoking women, the association between domestic incense use and lung cancer risk has been inconsistent. We conducted a systematic review of PubMed articles authored between 1969 and August 25, 2015 before performing a manual review of each study, and found a total of seven published studies on this topic. Most of the studies are case-control in design and did not further stratify by sex and smoking status. Of the seven studies, three reported positive associations, three reported null associations and one study found a negative association between incense use and lung cancer. Only one study reported estimates for non-smoking women. Future studies should be larger in sample size, stratify by both sex and smoking status in their analyses, and collect more detailed information on incense use in order to facilitate the understanding of the association between domestic incense use and lung cancer risk among non-smoking women in Asia.

Lung cancer risk stratification using methylation profile in the oral epithelium

2018 ◽  
Vol 27 (2) ◽  
pp. 87-92 ◽  
Author(s):  
Hiroaki Harada ◽  
Kazuaki Miyamaoto ◽  
Masami Kimura ◽  
Tetsuro Ishigami ◽  
Kiyomi Taniyama ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Cancer Risk ◽  
Risk Stratification ◽  
Lung Cancer Risk ◽  
Cancer Risk Assessment ◽  
Oral Epithelium ◽  
Specific Gene ◽  
Aberrant Methylation ◽  
Cancer Genes

Background Assuming that the entire airway is affected by the same inhaled carcinogen, similar molecular alterations may occur in the lung and oral cavity. Thus, we hypothesized that DNA methylation profiles in the oral epithelium may be a promising biomarker for lung cancer risk stratification. Methods A methylation-specific polymerase chain reaction was performed on oral epithelium from 16 patients with lung cancer and 32 controls without lung cancer. Genes showing aberrant methylation profiles in the oral epithelium were compared between patients and controls. Results The analysis revealed that HOXD11 and PCDHGB6 were methylated more frequently in patients than in controls ( p = 0.0055 and p = 0.0247, respectively). Combined analyses indicated that 8 of 16 (50%) patients and 3 of 32 (9.4%) controls showed DNA methylation in both genes ( p = 0.0016). Among the population limited to current and former smokers, 6 of 11 (54.5%) patients showed methylation in both genes, compared to 1 of 17 (5.9%) controls ( p = 0.0037). In a subgroup analysis limited to the population above 50-years old, 8 of 16 (50%) patients and 2 of 16 (12.5%) controls showed methylation in both genes ( p = 0.0221). Conclusions The results of this study indicate that specific gene methylation in the oral epithelium might be a promising biomarker for lung cancer risk assessment, especially among smokers. Risk stratification through the analysis of DNA methylation profiles in the oral epithelium may be a useful and less invasive first-step approach in an efficient two-step lung cancer screening strategy.

scholarly journals Association of FOXO3 Blood DNA Methylation with Cancer Risk, Cancer Survival, and Mortality

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3384
Author(s):  
Chenglong Yu ◽  
Allison M. Hodge ◽  
Ee Ming Wong ◽  
Jihoon Eric Joo ◽  
Enes Makalic ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Cancer Risk ◽  
Cancer Survival ◽  
Conditional Logistic Regression ◽  
B Cell Lymphoma ◽  
Case Control ◽  
Case Control Studies ◽  
Cox Models ◽  
Total N

Genetic variants in FOXO3 are associated with longevity. Here, we assessed whether blood DNA methylation at FOXO3 was associated with cancer risk, survival, and mortality. We used data from eight prospective case–control studies of breast (n = 409 cases), colorectal (n = 835), gastric (n = 170), kidney (n = 143), lung (n = 332), prostate (n = 869), and urothelial (n = 428) cancer and B-cell lymphoma (n = 438). Case–control pairs were matched on age, sex, country of birth, and smoking (lung cancer study). Conditional logistic regression was used to assess associations between cancer risk and methylation at 45 CpGs of FOXO3 included on the HumanMethylation450 assay. Mixed-effects Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations with cancer survival (total n = 2286 deaths). Additionally, using data from 1088 older participants, we assessed associations of FOXO3 methylation with overall and cause-specific mortality (n = 354 deaths). Methylation at a CpG in the first exon region of FOXO3 (6:108882981) was associated with gastric cancer survival (HR = 2.39, 95% CI: 1.60–3.56, p = 1.9 × 10−5). Methylation at three CpGs in TSS1500 and gene body was associated with lung cancer survival (p < 6.1 × 10−5). We found no evidence of associations of FOXO3 methylation with cancer risk and mortality. Our findings may contribute to understanding the implication of FOXO3 in longevity.

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