AHRR methylation predicts smoking status and smoking intensity in both saliva and blood DNA

Philibert, Robert A.; Dogan, Meeshanthini V.; Beach, Steven R. H.; Mills, James A.; Long, Jeffrey D.

doi:10.1002/ajmg.b.32760

Cited by 64 publications

(77 citation statements)

References 41 publications

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“…Still, the actual consumption of cigarettes that these cotinine levels represent may be lower. In our studies of adults who only smoked cigarettes that used this same ELISA assay, the same methylation level corresponded to~2 cigarettes per day [15]. Furthermore, the majority of the 19 W3 subjects, whose data is given in Fig.…”

Section: Discussionmentioning

confidence: 65%

“…Dozens of genome wide studies have suggested that DNA methylation approaches may address some of these limitations [13,14]. Building on these studies, we and others have shown that single assessments of blood or saliva DNA methylation status at cg05575921, a CpG residue in the aryl hydrocarbon repressor receptor (AHRR) locus, is extremely sensitive to regular adult smoking [15,16]. Furthermore, in preliminary work, we have shown that saliva DNA assessment of cg05575921 predicts adolescent smoking status [17].…”

Section: Introductionmentioning

confidence: 83%

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Refinement of cg05575921 demethylation response in nascent smoking

et al. 2020

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The initiation of adolescent smoking is difficult to detect using carbon monoxide or cotinine assays. Previously, we and others have shown that the methylation of cg05575921 is an accurate predictor of adult smoking status. But the dose and time dependency of the demethylation response to smoking initiation in adolescents is not yet well understood. To this end, we conducted three consecutive annual in-person interviews and biological samplings of 448 high school students (wave 1 (W1)-wave 3 (W3)). At W1 (n = 448), 62 subjects reported using tobacco and 72 subjects reported using cannabis at least once in their lifetime with 38 and 20 subjects having a positive cotinine and cannabinoid levels, respectively, at W1 intake. At W3 (n = 383), 67 subjects reported using tobacco and 60 subjects reported using cannabis at least once with 75 and 60 subjects having positive cotinine and cannabinoid levels, respectively, at W3. Subjects with undetectable cotinine levels at all three-time waves had stable levels of cg05575921 methylation throughout the study (88.7% at W1 and 88.8% at W3, n = 149), while subjects with positive cotinine levels at all 3 time points manifested a steady decrease in cg05575921 methylation (81.8% at W1 and 71.3% at the W3, n = 12). In those subjects with an affirmative smoking self-report at W3 (n = 17), the amount of demethylation at cg05575921 was correlated with time and intensity of smoking. We conclude that cg05575921 methylation is a sensitive, dose-dependent indicator of early stages of smoking, and may help to identify smokers in the early stages of smoking.

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Section: Discussionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 83%

Refinement of cg05575921 demethylation response in nascent smoking

et al. 2020

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“…Although DNA methylation loci associated with numerous exposures have been identified, most have not been demonstrated to be able to act as markers. The exceptions, CpG markers for current smoking and current heavy alcohol intake, were identified in cohorts that used questionnaires that assessed detailed current and previous use, including type, quantity, frequency, and duration of use, age when first started using, and age when quitting (if applicable) [37,40,59,60]. Identification of epigenetic markers for additional personal exposures that may be associated with breast cancer risk would also require a robust characterization of the exposure and data analysis for potential associations with the peripheral blood epigenome.…”

Section: Proposed Approaches and Expected Resultsmentioning

confidence: 99%

“…These findings suggest that epigenetic signatures can represent a biological memory of past exposures and that such signatures may be retained in the exposed stem and progenitor cells [29]. More recently, AHRR hypomethylation in saliva was also shown to predict smoking with an AUC of 0.971 [40]. Thus, salivary DNA methylation may also serve as biomarkers of environmental exposures.…”

Section: Dna Methylation As Molecular Markers Of Environmental Exposuresmentioning

confidence: 86%

Epigenetic Biomarkers for Environmental Exposures and Personalized Breast Cancer Prevention

Park

2020

IJERPH

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Environmental and lifestyle factors are believed to account for >80% of breast cancers; however, it is not well understood how and when these factors affect risk and which exposed individuals will actually develop the disease. While alcohol consumption, obesity, and hormone therapy are some known risk factors for breast cancer, other exposures associated with breast cancer risk have not yet been identified or well characterized. In this paper, it is proposed that the identification of blood epigenetic markers for personal, in utero, and ancestral environmental exposures can help researchers better understand known and potential relationships between exposures and breast cancer risk and may enable personalized prevention strategies.

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“…In addition to being a predictor of smoking habits [52], AHRR cg05575921 methylation from whole blood or saliva DNA is a validated predictor of smokingrelated morbidity and mortality [35,49]. For instance, AHRR cg05575921 hypomethylation has been associated with enhanced carcinogenesis especially in the lungs [10,31,35,38].…”

Section: Discussionmentioning

confidence: 99%

AHRR cg05575921 methylation in relation to smoking and PM2.5 exposure among Taiwanese men and women

Tantoh

Chuang

et al. 2020

Clin Epigenet

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Background: Polycyclic aromatic hydrocarbon (PAH)-rich substances like cigarette smoke and PM 2.5 induce aryl hydrocarbon receptor (AHR)-mediated aryl hydrocarbon receptor repressor (AHRR) methylation. AHRR cg05575921 and coagulation factor II (thrombin) receptor-like 3 (F2RL3) cg03636183 methylation patterns are well-established biomarkers for smoking. Even though AHRR cg05575921 methylation has recently been associated with PM 2.5 , the interaction between smoking and PM 2.5 on AHRR methylation is yet to be fully explored. We evaluated AHRR and F2RL3 CpG sites to identify potential significant markers in relation to PM 2.5 and smoking in Taiwanese adults. Methods: DNA methylation and smoking data of 948 participants aged 30-70 years were obtained from the Taiwan Biobank Database (2008-2015), while PM 2.5 data were obtained from the Air Quality Monitoring Database (2006-2011). Results: Smoking and PM 2.5 were independently associated with hypomethylation (lower levels) of AHRR cg05575921, AHRR cg23576855, F2RL3 cg03636183, and F2LR3 cg21911711 after multiple-comparison correction (Bonferroni P < 0.00028409). Cg05575921 was the most hypomethylated AHRR CpG site, while cg03636183 was the most hypomethylated F2RL3 CpG site. Overall, cg05575921 was the most hypomethylated CpG site: β = − 0.03909, P < 0.0001; − 0.17536, P < 0.0001 for former and current smoking, respectively (P-trend smoking < 0.0001) and − 0.00141, P < 0.0001 for PM 2.5. After adjusting for F2RL3 cg03636183, smoking and PM 2.5 remained significantly associated with cg05575921 hypomethylation: β − 0.02221, P < 0.0001; − 0.11578, P < 0.0001 for former and current smoking, respectively (P-trend smoking < 0.0001) and − 0.0070, P = 0.0120 for PM 2.5. After stratification by sex, smoking and PM 2.5 remained associated (P < 0.05) with cg05575921 hypomethylation in both men (β = − 0.04274, − 0.17700, and − 0.00163 for former smoking, current smoking, and PM 2.5 , respectively) and women (β = − 0.01937, − 0.17255, and − 0.00105 for former smoking, current smoking, and PM 2.5 , respectively). After stratification by residential area, former and current smoking remained associated (P < 0.05) with cg05575921 hypomethylation: β = − 0.03918 and − 0.17536,

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AHRR methylation predicts smoking status and smoking intensity in both saliva and blood DNA

Cited by 64 publications

References 41 publications

Refinement of cg05575921 demethylation response in nascent smoking

Refinement of cg05575921 demethylation response in nascent smoking

Epigenetic Biomarkers for Environmental Exposures and Personalized Breast Cancer Prevention

AHRR cg05575921 methylation in relation to smoking and PM2.5 exposure among Taiwanese men and women

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