Dataset Information

Association of internal smoking dose with blood DNA methylation in three racial/ethnic populations.

ABSTRACT: BACKGROUND:Lung cancer is the leading cause of cancer-related death. While cigarette smoking is the primary cause of this malignancy, risk differs across racial/ethnic groups. For the same number of cigarettes smoked, Native Hawaiians compared to whites are at greater risk and Japanese Americans are at lower risk of developing lung cancer. DNA methylation of specific CpG sites (e.g., in AHRR and F2RL3) is the most common blood epigenetic modification associated with smoking status. However, the influence of internal smoking dose, measured by urinary nicotine equivalents (NE), on DNA methylation in current smokers has not been investigated, nor has a study evaluated whether for the same smoking dose, circulating leukocyte DNA methylation patterns differ by race. METHODS:We conducted an epigenome-wide association study (EWAS) of NE in 612 smokers from three racial/ethnic groups: whites (n = 204), Native Hawaiians (n = 205), and Japanese Americans (n = 203). Genome-wide DNA methylation profiling of blood leukocyte DNA was measured using the Illumina 450K BeadChip array. Average ? value, the ratio of signal from a methylated probe relative to the sum of the methylated and unmethylated probes at that CpG, was the dependent variables in linear regression models adjusting for age, sex, race (for pan-ethnic analysis), and estimated cell-type distribution. RESULTS:We found that NE was significantly associated with six differentially methylated CpG sites (Bonferroni corrected p < 1.48 × 10-7): four in or near the FOXK2, PBX1, FNDC7, and FUBP3 genes and two in non-annotated genetic regions. Higher levels of NE were associated with increasing methylation beta-valuesin all six sites. For all six CpG sites, the association was only observed in Native Hawaiians, suggesting that the influence of smoking dose on DNA methylation patterns is heterogeneous across race/ethnicity (p interactions < 8.8 × 10-8). We found two additional CpG sites associated with NE in only Native Hawaiians. CONCLUSIONS:In conclusion, internal smoking dose was associated with increased DNA methylation in circulating leukocytes at specific sites in Native Hawaiian smokers but not in white or Japanese American smokers.

SUBMITTER: Park SL

PROVIDER: S-EPMC6108111 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Association of internal smoking dose with blood DNA methylation in three racial/ethnic populations.

Park Sungshim L SL Patel Yesha M YM Loo Lenora W M LWM Mullen Daniel J DJ Offringa Ite A IA Maunakea Alika A Stram Daniel O DO Siegmund Kimberly K Murphy Sharon E SE Tiirikainen Maarit M Le Marchand Loïc L

Clinical epigenetics 20180823 1

<h4>Background</h4>Lung cancer is the leading cause of cancer-related death. While cigarette smoking is the primary cause of this malignancy, risk differs across racial/ethnic groups. For the same number of cigarettes smoked, Native Hawaiians compared to whites are at greater risk and Japanese Americans are at lower risk of developing lung cancer. DNA methylation of specific CpG sites (e.g., in AHRR and F2RL3) is the most common blood epigenetic modification associated with smoking status. Howev ...[more]

PMID: 30139389

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Project description:Racial/ethnic groups appear to differ on quit success and withdrawal is a key factor in cessation failure, yet little is known about racial/ethnic differences in withdrawal symptoms. This study of US adults examined racial/ethnic differences in current smokers' report of withdrawal symptoms and the relationship between withdrawal symptoms and quitting smoking 3 years later.Using data from the National Epidemiologic Survey on Alcohol and Related Conditions (Wave 1, 2001-2001; Wave 2, 2004-2005), analyses were conducted on participants who identified as non-Hispanic White, non-Hispanic Black, or Hispanic; reported current cigarette smoking at Wave 1; and provided smoking status information at Wave 2 (n = 7981). Withdrawal symptoms during past quit attempts were assessed at Wave 1.Among Wave 1 current smoking adults, non-Hispanic White respondents were more likely than non-Hispanic Black and Hispanic respondents to report experiencing at least one withdrawal symptom, seven out of eight withdrawal symptoms, withdrawal-related discomfort, and withdrawal-related distress (ps < .0001). While withdrawal symptoms were associated with a lower odds of quitting smoking for all groups, a stronger relationship between number of symptoms and lower odds of quitting was evident among non-Hispanic White compared to non-Hispanic Black respondents (interaction β = 0.065, p = .0001). For non-Hispanic White participants, each additional withdrawal symptom was associated with a 6% decrease in the odds of quitting.Withdrawal symptoms were more commonly reported by non-Hispanic White adults than non-Hispanic Black and Hispanic adults and appeared to have a greater impact on failure to quit smoking for non-Hispanic White compared to non-Hispanic Black adults.To our knowledge, this is the first study to use prospective, longitudinal data to examine the relationship between race and withdrawal symptoms and the impact of withdrawal symptoms on quitting smoking among adults in the United States. Non-Hispanic White adults were more likely to report withdrawal symptoms and there was a stronger relationship between greater number of withdrawal symptoms and lower odds of quitting for non-Hispanic White adults compared to non-Hispanic Black adults. Developing a better understanding of racial/ethnic differences in withdrawal and cessation can help to tailor efforts to improve outcomes for smokers in various racial/ethnic groups.

Project description:We conducted a genome-wide association study of blood DNA methylation and smoking, attempted replication of previously discovered associations, and assessed the reversibility of smoking-associated methylation changes. DNA methylation was measured in baseline peripheral blood samples for 5,044 participants in the Melbourne Collaborative Cohort Study. For 1,032 participants, these measures were repeated using blood samples collected at follow-up, a median of 11 years later. A cross-sectional analysis of the association between smoking and DNA methylation and a longitudinal analysis of changes in smoking status and changes in DNA methylation were conducted. We used our cross-sectional analysis to replicate previously reported associations for current (N = 3,327) and former (N = 172) smoking. A comprehensive smoking index accounting for the biological half-life of smoking compounds and several aspects of smoking history was constructed to assess the reversibility of smoking-induced methylation changes. This measure of lifetime exposure to smoking allowed us to detect more associations than comparing current with never smokers. We identified 4,496 cross-sectional associations at P < 10-7, including 3,296 annotated to 1,326 genes that were not previously implicated in smoking-associated DNA methylation changes at this significance threshold. We replicated the majority of previously reported associations (P < 10-7) for current and former smokers. In our data, we observed for former smokers a substantial degree of return to the methylation levels of never smokers, compared with current smokers (median: 74%, IQR = 63-86%), corresponding to small values (median: 2.75, IQR = 1.5-5.25) for the half-life parameter of the comprehensive smoking index. Longitudinal analyses identified 368 sites at which methylation changed upon smoking cessation. Our study demonstrates the usefulness of the comprehensive smoking index to detect associations between smoking and DNA methylation at CpGs across the genome, replicates the vast majority of previously reported associations, and quantifies the reversibility of smoking-induced methylation changes.

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Association of internal smoking dose with blood DNA methylation in three racial/ethnic populations.

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Association of internal smoking dose with blood DNA methylation in three racial/ethnic populations.

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