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.

scholarly journals Epigenetic drift association with cancer risk and survival, and modification by sex

2021 ◽  
Author(s):  
Chenglong Yu ◽  
Ee Ming Wong ◽  
Jihoon Eric Joo ◽  
Allison M. Hodge ◽  
Enes Makalic ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cancer Risk ◽  
Conditional Logistic Regression ◽  
B Cell Lymphoma ◽  
Case Control ◽  
Case Control Studies ◽  
Cox Models ◽  
Age Related ◽  
Matched Case ◽  
Age And Sex

AbstractTo investigate age- and sex-specific DNA methylation alterations related to cancer risk and survival, we used matched case-control studies of colorectal (N=835), gastric (N=170), kidney (N=143), lung (N=332), prostate (N=869) and urothelial (N=428) cancers, and mature B-cell lymphoma (N=438). Linear mixed-effects models were conducted to identify age-, sex- and age-by-sex-associated methylation markers using a discovery (controls) - replication (cases) strategy. Replication was further examined using summary statistics from Generation Scotland (GS). Associations between replicated markers and risk of and survival from cancer were assessed using conditional logistic regression and Cox models (hazard ratios [HR]), respectively. We found 32,659, 23,141 and 48 CpGs with replicated associations for age, sex and age-by-sex, respectively. The replication rates (GS summary data) for these CpGs were 94%, 86% and 91%, respectively. Significant signals for cancer risk and survival were identified at some individual age-related CpGs. There was a strong negative trend in the association between epigenetic drift and risk of colorectal cancer. Two CpGs overlapping TMEM49 and ARX genes were associated with survival of overall (HR=0.91, P=7.7×10−4) and colorectal (HR=1.52, P=1.8×10−4) cancer, respectively, with significant age-by-sex interaction. Our results may provide markers for cancer early detection and prognosis prediction.Simple SummaryAgeing is the strongest cancer risk factor, and men and women exhibit disparate risk profiles in terms of incidence and survival. DNA methylation is known to strongly vary by age and sex. Epigenetic drift refers to age-related DNA methylation changes and the tendency for increasing discordance between epigenomes over time, but it remains unknown to what extent the epigenetic drift might contribute to cancer risk and survival. The aims of this study were to identify age-associated, sex-associated and sexually dimorphic age-associated (age-by-sex-associated) DNA methylation markers and investigate whether age- and age-by-sex-associated markers are associated with cancer risk and survival. Our study, which used a total of 3,215 matched case-control pairs with DNA methylation in pre-diagnostic blood, is the first large study to examine the association between sex-specific epigenetic drift and cancer development and progression. The results may be useful for cancer early diagnosis and prediction of prognosis.

scholarly journals Epigenetic Drift Association with Cancer Risk and Survival, and Modification by Sex

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1881
Author(s):  
Chenglong Yu ◽  
Ee Ming Wong ◽  
Jihoon Eric Joo ◽  
Allison M. Hodge ◽  
Enes Makalic ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Conditional Logistic Regression ◽  
B Cell Lymphoma ◽  
Case Control Studies ◽  
Cox Models ◽  
Cancer Early Detection ◽  
Age Related ◽  
Hazard Ratios ◽  
Generation Scotland ◽  
Matched Case

To investigate age- and sex-specific DNA methylation alterations related to cancer risk and survival, we used matched case–control studies of colorectal (n = 835), gastric (n = 170), kidney (n = 143), lung (n = 332), prostate (n = 869) and urothelial (n = 428) cancers, and mature B-cell lymphoma (n = 438). Linear mixed-effects models were conducted to identify age-, sex- and age-by-sex-associated methylation markers using a discovery (controls)-replication (cases) strategy. Replication was further examined using summary statistics from Generation Scotland (GS). Associations between replicated markers and risk of and survival from cancer were assessed using conditional logistic regression and Cox models (hazard ratios (HR)), respectively. We found 32,659, 23,141 and 48 CpGs with replicated associations for age, sex and age-by-sex, respectively. The replication rates for these CpGs using GS summary data were 94%, 86% and 91%, respectively. Significant associations for cancer risk and survival were identified at some individual age-related CpGs. Opposite to previous findings using epigenetic clocks, there was a strong negative trend in the association between epigenetic drift and risk of colorectal cancer. Methylation at two CpGs overlapping TMEM49 and ARX genes was associated with survival of overall (HR = 0.91, p = 7.7 × 10−4) and colorectal (HR = 1.52, p = 1.8 × 10−4) cancer, respectively, with significant age-by-sex interaction. Our results may provide markers for cancer early detection and prognosis prediction.

scholarly journals A systematic assessment of the association between frequently prescribed medicines and the risk of common cancers: a series of nested case-control studies

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
R. D. McDowell ◽  
C. Hughes ◽  
P. Murchie ◽  
C. Cardwell
Keyword(s):  
Cancer Risk ◽  
Conditional Logistic Regression ◽  
Exposure Dose ◽  
Case Control ◽  
Case Control Studies ◽  
Systematic Assessment ◽  
Exposure Response ◽  
Prescribed Medicines ◽  
Nested Case Control ◽  
Novel Associations

Abstract Background Studies systematically screening medications have successfully identified prescription medicines associated with cancer risk. However, adjustment for confounding factors in these studies has been limited. We therefore investigated the association between frequently prescribed medicines and the risk of common cancers adjusting for a range of confounders. Methods A series of nested case-control studies were undertaken using the Primary Care Clinical Informatics Unit Research (PCCIUR) database containing general practice (GP) records from Scotland. Cancer cases at 22 cancer sites, diagnosed between 1999 and 2011, were identified from GP records and matched with up to five controls (based on age, gender, GP practice and date of registration). Odds ratios (OR) and 95% confidence intervals (CI) comparing any versus no prescriptions for each of the most commonly prescribed medicines, identified from prescription records, were calculated using conditional logistic regression, adjusting for comorbidities. Additional analyses adjusted for smoking use. An association was considered a signal based upon the magnitude of its adjusted OR, p-value and evidence of an exposure-response relationship. Supplementary analyses were undertaken comparing 6 or more prescriptions versus less than 6 for each medicine. Results Overall, 62,109 cases and 276,580 controls were included in the analyses and a total of 5622 medication-cancer associations were studied across the 22 cancer sites. After adjusting for comorbidities 2060 medicine-cancer associations for any prescription had adjusted ORs greater than 1.25 (or less than 0.8), 214 had a corresponding p-value less than or equal to 0.01 and 118 had evidence of an exposure-dose relationship hence meeting the criteria for a signal. Seventy-seven signals were identified after additionally adjusting for smoking. Based upon an exposure of 6 or more prescriptions, there were 118 signals after adjusting for comorbidities and 82 after additionally adjusting for smoking. Conclusions In this study a number of novel associations between medicine and cancer were identified which require further clinical and epidemiological investigation. The majority of medicines were not associated with an altered cancer risk and many identified signals reflected known associations between medicine and cancer.

scholarly journals Lung cancer risk among bricklayers in a pooled analysis of case–control studies

2014 ◽  
Vol 136 (2) ◽  
pp. 360-371 ◽  
Author(s):  
Dario Consonni ◽  
Sara De Matteis ◽  
Angela C. Pesatori ◽  
Pier Alberto Bertazzi ◽  
Ann C. Olsson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Lung Cancer Risk ◽  
Pooled Analysis ◽  
Case Control ◽  
Case Control Studies

scholarly journals Dietary patterns and breast or lung cancer risk: A pooled analysis of 2 case-control studies in north-eastern Poland

2017 ◽  
Vol 26 (9) ◽  
pp. 1367-1375 ◽  
Author(s):  
Beata Krusińska ◽  
Iwona Hawrysz ◽  
Małgorzata Słowińska ◽  
Lidia Wądołowska ◽  
Maciej Biernacki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Dietary Patterns ◽  
Lung Cancer Risk ◽  
Pooled Analysis ◽  
Case Control ◽  
Case Control Studies ◽  
North Eastern

scholarly journals The MPO−463G>A Polymorphism and Lung Cancer Risk: A Meta-Analysis Based on 22 Case–Control Studies

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e65778 ◽  
Author(s):  
Jun-Ping Yang ◽  
Wen-Bo Wang ◽  
Xiao-Xi Yang ◽  
Lei Yang ◽  
Li Ren ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Lung Cancer Risk ◽  
Meta Analysis ◽  
Case Control ◽  
Case Control Studies

scholarly journals ERCC2/XPD Lys751Gln and Asp312Asn Gene Polymorphism and Lung Cancer Risk: A Meta-Analysis Involving 22 Case–Control Studies

2010 ◽  
Vol 5 (9) ◽  
pp. 1337-1345 ◽  
Author(s):  
Ping Zhan ◽  
Qin Wang ◽  
Shu-Zhen Wei ◽  
Jing Wang ◽  
Qian Qian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Gene Polymorphism ◽  
Lung Cancer Risk ◽  
Meta Analysis ◽  
Case Control ◽  
Case Control Studies

Mechanistic modelling in large case-control studies of lung cancer risk from smoking

2002 ◽  
Vol 21 (20) ◽  
pp. 3055-3070 ◽  
Author(s):  
W. F. Heidenreich ◽  
J. Wellmann ◽  
P. Jacob ◽  
H. E. Wichmann
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Lung Cancer Risk ◽  
Case Control ◽  
Case Control Studies ◽  
Mechanistic Modelling ◽  
Large Case
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