<i>LINE1</i>methylation levels associated with increased bladder cancer risk in pre-diagnostic blood DNA among US (PLCO) and European (ATBC) cohort study participants

Andreotti, Gabriella; Karami, Sara; Pfeiffer, Ruth M.; Hurwitz, Lauren M.; Liao, Linda M.; Weinstein, Stephanie J.; Albanês, Demetrius; Virtamo, Jarmo; Silverman, Debra T.; Rothman, Nathaniel; Moore, Lee E.

doi:10.4161/epi.27386

Cited by 31 publications

(39 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…7 A similar association was observed in the prospective PLCO cohort, in which smoking was shown to modify the association between high vs. low LINE1 methylation levels and future bladder cancer risk; the association was significant in males, particularly in male smokers. 6 In contrast, in studies that have used post-diagnostic samples cancer risks were higher among never smokers with lower methylation levels. [19][20][21] With regards to our findings, higher cancer risk among smokers could imply that prior to renal cancer development, cells with higher methylation levels may be more resistant to the genotoxic effects of smoking compared to those with lower methylation levels.…”

Section: Discussionmentioning

confidence: 95%

“…7 Most recently, having higher LINE1 %5mC levels were reported to be a strong risk factor for the development of bladder cancer in analyses of pre-diagnostic blood DNAs among participants in the ATBC and PLCO cohorts. 6 Other epidemiological studies that have investigated other cancer types in relation to LINE1 methylation levels in pre-diagnostic blood DNA samples have been less consistent for non-urologic malignancies. [15][16][17][18] The effect of cigarette smoking on methylation levels and RCC risk was not initially apparent in the population as a whole.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, PLCO included both male and female smokers and non-smokers, whereas ATBC included only male smokers that have generally demonstrated higher LINE1 methylation levels compared to females. 2,6 Strengths of our study include its prospective design and use of high quality questionnaire data collected prior to cancer diagnosis thus, reduced the risk of recall bias. The random selection of other cancer cases as controls ensured that our control population was not healthier than all study controls and increased the generalizability of our results.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, long interspersed nucleotide element (LINE1) methylation levels in blood DNA have been examined in relation to risk of several cancers. [2][3][4][5][6] To our knowledge, only one case-control study, conducted in Central and Eastern Europe, has assessed this association in relation to renal cell carcinoma (RCC) risk. 7 In that study, LINE1 methylation of bisulfite-converted genomic DNA isolated from leukocytes observed that higher global DNA LINE1 methylation levels were associated with an increased risk of RCC.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

LINE1 methylation levels in pre-diagnostic leukocyte DNA and future renal cell carcinoma risk

et al. 2015

Self Cite

View full text Add to dashboard Cite

E Moore (2015) LINE1 methylation levels in pre-diagnostic leukocyte DNA and future renal cell carcinoma risk, Epigenetics, 10:4, 282-292, DOI: 10.1080/15592294.2015 Higher levels of LINE1 methylation in blood DNA have been associated with increased kidney cancer risk using postdiagnostically collected samples; however, this association has never been examined using pre-diagnostic samples. We examined the association between LINE1 %5mC and renal cell carcinoma (RCC) risk using pre-diagnostic blood DNA from the United States-based, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (215 cases/436 controls), and the Alpha-tocopherol, Beta-carotene Cancer Prevention Study (ATBC) of Finnish male smokers (191 cases/575 controls). Logistic regression adjusted for age at blood draw, study center, pack-years of smoking, body mass index, hypertension, dietary alcohol intake, family history of cancer, and sex was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) using cohort and sex-specific methylation categories. In PLCO, higher, although non-significant, RCC risk was observed for participants at or above median methylation level (M2) compared to those below the median (M1) (OR: 1.37, 95% CI: 0.96-1.95). The association was stronger in males (M2 vs. M1, OR: 1.54, 95% CI: 1.00-2.39) and statistically significant among male smokers (M2 vs. M1, OR: 2.60, 95% CI: 1.46-4.63). A significant interaction for smoking was also detected (P-interaction: 0.01). No association was found among females or female smokers. Findings for male smokers were replicated in ATBC (M2 vs. M1, OR: 1.31, 95% CI: 1.07-1.60). In a pooled analysis of PLCO and ATBC male smokers (281cases/755controls), the OR among subjects at or above median methylation level (M2) compared to those below the median (M1) was 1.89 (95% CI: 1.34-2.67, P-value: 3 x 10 -4 ); a trend was also observed by methylation quartile (P-trend: 0.002). These findings suggest that higher LINE1 methylation levels measured prior to cancer diagnosis may be a biomarker of future RCC risk among male smokers.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

LINE1 methylation levels in pre-diagnostic leukocyte DNA and future renal cell carcinoma risk

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…In another case-control study, no association was observed between LINE1 methylation levels and bladder cancer risk (Wilhelm et al 2010 ). Findings from two nested case-control studies conducted within the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial (PLCO) and the AlphaTocopherol, Beta-Carotene Cancer Prevention (ATBC) Cohorts reported that higher levels of LINE1 methylation were associated with bladder cancer risk using prediagnostically collected blood DNA (Andreotti et al 2013 ). In the PLCO study (a study that included male/female smokers/nonsmokers), smoking did not modify the association between high compared to low LINE1 methylation levels and future bladder cancer risk, but the magnitude of risk was signifi cant in males, particularly male smokers.…”

Section: Epigenetic Alterations and Environmental Exposuresmentioning

confidence: 99%

Environmental Epigenomics: Applications of Epigenetic Biomarkers to Investigate Epigenetic Alterations from Environmental Exposures

Moore

Karami

Rusiecki

2015

Molecular and Integrative Toxicology

Self Cite

View full text Add to dashboard Cite

Over the past decade, evidence has shown that epigenetic mechanisms play an important role in human disease susceptibility and cancer. Studies of potential human carcinogens have been expanded to include those that do not appear to damage DNA directly but rather alter gene expression patterns through epigenetic mechanisms such as alterations in DNA methylation, histone modifi cations/chromatin alterations, and microRNA. Given that almost 25 % of all human diseases are estimated to be caused by environmental exposures, here we review current studies of xenobiotic exposures for which there is growing mechanistic evidence for indirect DNA alteration through epigenetic mechanisms. Also described are common variations in genes that may modify epigenetic alterations in blood and tumor DNA. Epidemiological methods used to incorporate epigenetic alterations into studies of disease etiology as well as current methods used to apply and critically evaluate study results reporting associations between environmental exposure and disease are described.

show abstract

Smoking is associated with hypermethylation of the APC 1A promoter in colorectal cancer: the ColoCare Study

Barrow

Klett

Tóth

et al. 2017

The Journal of Pathology

View full text Add to dashboard Cite

Smoking tobacco is a known risk factor for the development of colorectal cancer, and for mortality associated with the disease. Smoking has been reported to be associated with changes in DNA methylation in blood and in lung tumour tissues, although there has been scant investigation of how epigenetic factors may be implicated in the increased risk of developing colorectal cancer. To identify epigenetic changes associated with smoking behaviours, we performed epigenome-wide analysis of DNA methylation in colorectal tumours from 36 never smokers, 47 former smokers and 13 active smokers, and adjacent mucosa from 49 never smokers, 64 former smokers and 18 active smokers. Our analyses identified 15 CpG sites within the APC 1A promoter that were significantly hypermethylated and 14 CpG loci within the NFATC1 gene body that were significantly hypomethylated (pLIS<1×10−5) in tumours of active smokers. The APC 1A promoter was hypermethylated in 7 of 36 tumours from never smokers (19%), 12 of 47 tumours from former smokers (26%), and 8 of 13 tumours from active smokers (62%). Promoter hypermethylation was positively associated with duration of smoking (Spearman rank correlation, ρ=0.26, p=0.03) and was confined to tumours, with hypermethylation never being observed in adjacent mucosa. Further analysis of adjacent mucosa revealed significant hypomethylation of four loci associated with the TNXB gene in tissue from active smokers. Our findings provide exploratory evidence for hypermethylation of the key tumour suppressor gene APC being implicated in smoking-associated colorectal carcinogenesis. Further work is required to establish the validity of our observations in independent cohorts.

show abstract

LINE1methylation levels associated with increased bladder cancer risk in pre-diagnostic blood DNA among US (PLCO) and European (ATBC) cohort study participants

Cited by 31 publications

References 27 publications

LINE1 methylation levels in pre-diagnostic leukocyte DNA and future renal cell carcinoma risk

LINE1 methylation levels in pre-diagnostic leukocyte DNA and future renal cell carcinoma risk

Environmental Epigenomics: Applications of Epigenetic Biomarkers to Investigate Epigenetic Alterations from Environmental Exposures

Smoking is associated with hypermethylation of the APC 1A promoter in colorectal cancer: the ColoCare Study

Contact Info

Product

Resources

About