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  1. Article ; Online: A causal inference study: The impact of the combined administration of Donepezil and Memantine on decreasing hospital and emergency department visits of Alzheimer's disease patients.

    Yaghmaei, Ehsan / Pierce, Albert / Lu, Hongxia / Patel, Yesha M / Ehwerhemuepha, Louis / Rezaie, Ahmad / Sajjadi, Seyed Ahmad / Rakovski, Cyril

    PloS one

    2023  Volume 18, Issue 9, Page(s) e0291362

    Abstract: Alzheimer's disease is the most common type of dementia that currently affects over 6.5 million people in the U.S. Currently there is no cure and the existing drug therapies attempt to delay the mental decline and improve cognitive abilities. Two of the ... ...

    Abstract Alzheimer's disease is the most common type of dementia that currently affects over 6.5 million people in the U.S. Currently there is no cure and the existing drug therapies attempt to delay the mental decline and improve cognitive abilities. Two of the most commonly prescribed such drugs are Donepezil and Memantine. We formally tested and confirmed the presence of a beneficial drug-drug interaction of Donepezil and Memantine using a causal inference analysis. We applied doubly robust estimators to one of the largest and high-quality medical databases to estimate the effect of two commonly prescribed Alzheimer's disease (AD) medications, Donepezil and Memantine, on the average number of hospital or emergency department visits per year among patients diagnosed with AD. Our results show that, compared to the absence of medication scenario, the Memantine monotherapy, and the Donepezil monotherapy, the combined use of Donepezil and Memantine treatment significantly reduces the average number of hospital or emergency department visits per year by 0.078 (13.8%), 0.144 (25.5%), and 0.132 days (23.4%), respectively. The assessed decline in the average number of hospital or emergency department visits per year is consequently associated with a substantial reduction in medical costs. As of 2022, according to the Alzheimer's Disease Association, there were over 6.5 million individuals aged 65 and older living with AD in the US alone. If patients who are currently on no drug treatment or using either Donepezil or Memantine alone were switched to the combined used of Donepezil and Memantine therapy, the average number of hospital or emergency department visits could decrease by over 613 thousand visits per year. This, in turn, would lead to a remarkable reduction in medical expenses associated with hospitalization of AD patients in the US, totaling over 940 million dollars per year.
    MeSH term(s) Humans ; Alzheimer Disease/drug therapy ; Donepezil/therapeutic use ; Memantine/therapeutic use ; Hospitals ; Emergency Service, Hospital
    Chemical Substances Donepezil (8SSC91326P) ; Memantine (W8O17SJF3T)
    Language English
    Publishing date 2023-09-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0291362
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Epigenome-wide association study of total nicotine equivalents in multiethnic current smokers from three prospective cohorts.

    Huang, Brian Z / Binder, Alexandra M / Quon, Brandon / Patel, Yesha M / Lum-Jones, Annette / Tiirikainen, Maarit / Murphy, Sharon E / Loo, Lenora / Maunakea, Alika K / Haiman, Christopher A / Wilkens, Lynne R / Koh, Woon-Puay / Cai, Qiuyin / Aldrich, Melinda C / Siegmund, Kimberly D / Hecht, Stephen S / Yuan, Jian-Min / Blot, William J / Stram, Daniel O /
    Le Marchand, Loïc / Park, Sungshim L

    American journal of human genetics

    2024  Volume 111, Issue 3, Page(s) 456–472

    Abstract: The impact of tobacco exposure on health varies by race and ethnicity and is closely tied to internal nicotine dose, a marker of carcinogen uptake. DNA methylation is strongly responsive to smoking status and may mediate health effects, but study of ... ...

    Abstract The impact of tobacco exposure on health varies by race and ethnicity and is closely tied to internal nicotine dose, a marker of carcinogen uptake. DNA methylation is strongly responsive to smoking status and may mediate health effects, but study of associations with internal dose is limited. We performed a blood leukocyte epigenome-wide association study (EWAS) of urinary total nicotine equivalents (TNEs; a measure of nicotine uptake) and DNA methylation measured using the MethylationEPIC v1.0 BeadChip (EPIC) in six racial and ethnic groups across three cohort studies. In the Multiethnic Cohort Study (discovery, n = 1994), TNEs were associated with differential methylation at 408 CpG sites across >250 genomic regions (p < 9 × 10
    MeSH term(s) Humans ; Smokers ; Nicotine ; Epigenesis, Genetic/genetics ; Epigenome ; Cohort Studies ; Prospective Studies ; Genome-Wide Association Study ; DNA Methylation/genetics ; CpG Islands/genetics ; Receptors, Peptide/genetics ; Receptors, G-Protein-Coupled/genetics ; MicroRNAs
    Chemical Substances Nicotine (6M3C89ZY6R) ; GPR15 protein, human ; Receptors, Peptide ; Receptors, G-Protein-Coupled ; MIRN383 microRNA, human ; MicroRNAs
    Language English
    Publishing date 2024-02-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 219384-x
    ISSN 1537-6605 ; 0002-9297
    ISSN (online) 1537-6605
    ISSN 0002-9297
    DOI 10.1016/j.ajhg.2024.01.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Analytical code sharing practices in biomedical research.

    Sharma, Nitesh Kumar / Ayyala, Ram / Deshpande, Dhrithi / Patel, Yesha M / Munteanu, Viorel / Ciorba, Dumitru / Fiscutean, Andrada / Vahed, Mohammad / Sarkar, Aditya / Guo, Ruiwei / Moore, Andrew / Darci-Maher, Nicholas / Nogoy, Nicole A / Abedalthagafi, Malak S / Mangul, Serghei

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Data-driven computational analysis is becoming increasingly important in biomedical research, as the amount of data being generated continues to grow. However, the lack of practices of sharing research outputs, such as data, source code and methods, ... ...

    Abstract Data-driven computational analysis is becoming increasingly important in biomedical research, as the amount of data being generated continues to grow. However, the lack of practices of sharing research outputs, such as data, source code and methods, affects transparency and reproducibility of studies, which are critical to the advancement of science. Many published studies are not reproducible due to insufficient documentation, code, and data being shared. We conducted a comprehensive analysis of 453 manuscripts published between 2016-2021 and found that 50.1% of them fail to share the analytical code. Even among those that did disclose their code, a vast majority failed to offer additional research outputs, such as data. Furthermore, only one in ten papers organized their code in a structured and reproducible manner. We discovered a significant association between the presence of code availability statements and increased code availability (p=2.71×10
    Language English
    Publishing date 2023-08-07
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.31.551384
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Quantitation of DNA Adducts Resulting from Acrolein Exposure and Lipid Peroxidation in Oral Cells of Cigarette Smokers from Three Racial/Ethnic Groups with Differing Risks for Lung Cancer.

    Park, Sungshim L / Le Marchand, Loic / Cheng, Guang / Balbo, Silvia / Chen, Menglan / Carmella, Steven G / Thomson, Nicole M / Lee, Younghan / Patel, Yesha M / Stram, Daniel O / Jensen, Joni / Hatsukami, Dorothy K / Murphy, Sharon E / Hecht, Stephen S

    Chemical research in toxicology

    2022  Volume 35, Issue 10, Page(s) 1914–1922

    Abstract: The Multiethnic Cohort Study has demonstrated that the risk for lung cancer in cigarette smokers among three ethnic groups is highest in Native Hawaiians, intermediate in Whites, and lowest in Japanese Americans. We hypothesized that differences in ... ...

    Abstract The Multiethnic Cohort Study has demonstrated that the risk for lung cancer in cigarette smokers among three ethnic groups is highest in Native Hawaiians, intermediate in Whites, and lowest in Japanese Americans. We hypothesized that differences in levels of DNA adducts in oral cells of cigarette smokers would be related to these differing risks of lung cancer. Therefore, we used liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry to quantify the acrolein-DNA adduct (8
    MeSH term(s) Acrolein/chemistry ; Acrylonitrile ; Cohort Studies ; DNA ; DNA Adducts ; Ethnicity ; Humans ; Lipid Peroxidation ; Lung Neoplasms/urine ; Nicotine/urine ; Purines ; Smokers ; Smoking ; Tobacco Products
    Chemical Substances DNA Adducts ; Purines ; Nicotine (6M3C89ZY6R) ; Acrolein (7864XYD3JJ) ; DNA (9007-49-2) ; Acrylonitrile (MP1U0D42PE)
    Language English
    Publishing date 2022-08-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 639353-6
    ISSN 1520-5010 ; 0893-228X
    ISSN (online) 1520-5010
    ISSN 0893-228X
    DOI 10.1021/acs.chemrestox.2c00171
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Multiethnic Prediction of Nicotine Biomarkers and Association With Nicotine Dependence.

    Bergen, Andrew W / McMahan, Christopher S / McGee, Stephen / Ervin, Carolyn M / Tindle, Hilary A / Le Marchand, Loïc / Murphy, Sharon E / Stram, Daniel O / Patel, Yesha M / Park, Sungshim L / Baurley, James W

    Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco

    2021  Volume 23, Issue 12, Page(s) 2162–2169

    Abstract: Introduction: The nicotine metabolite ratio and nicotine equivalents are measures of metabolism rate and intake. Genome-wide prediction of these nicotine biomarkers in multiethnic samples will enable tobacco-related biomarker, behavioral, and exposure ... ...

    Abstract Introduction: The nicotine metabolite ratio and nicotine equivalents are measures of metabolism rate and intake. Genome-wide prediction of these nicotine biomarkers in multiethnic samples will enable tobacco-related biomarker, behavioral, and exposure research in studies without measured biomarkers.
    Aims and methods: We screened genetic variants genome-wide using marginal scans and applied statistical learning algorithms on top-ranked genetic variants, age, ethnicity and sex, and, in additional modeling, cigarettes per day (CPD), (in additional modeling) to build prediction models for the urinary nicotine metabolite ratio (uNMR) and creatinine-standardized total nicotine equivalents (TNE) in 2239 current cigarette smokers in five ethnic groups. We predicted these nicotine biomarkers using model ensembles and evaluated external validity using dependence measures in 1864 treatment-seeking smokers in two ethnic groups.
    Results: The genomic regions with the most selected and included variants for measured biomarkers were chr19q13.2 (uNMR, without and with CPD) and chr15q25.1 and chr10q25.3 (TNE, without and with CPD). We observed ensemble correlations between measured and predicted biomarker values for the uNMR and TNE without (with CPD) of 0.67 (0.68) and 0.65 (0.72) in the training sample. We observed inconsistency in penalized regression models of TNE (with CPD) with fewer variants at chr15q25.1 selected and included. In treatment-seeking smokers, predicted uNMR (without CPD) was significantly associated with CPD and predicted TNE (without CPD) with CPD, time-to-first-cigarette, and Fagerström total score.
    Conclusions: Nicotine metabolites, genome-wide data, and statistical learning approaches developed novel robust predictive models for urinary nicotine biomarkers in multiple ethnic groups. Predicted biomarker associations helped define genetically influenced components of nicotine dependence.
    Implications: We demonstrate development of robust models and multiethnic prediction of the uNMR and TNE using statistical and machine learning approaches. Variants included in trained models for nicotine biomarkers include top-ranked variants in multiethnic genome-wide studies of smoking behavior, nicotine metabolites, and related disease. Association of the two predicted nicotine biomarkers with Fagerström Test for Nicotine Dependence items supports models of nicotine biomarkers as predictors of physical dependence and nicotine exposure. Predicted nicotine biomarkers may facilitate tobacco-related disease and treatment research in samples with genomic data and limited nicotine metabolite or tobacco exposure data.
    MeSH term(s) Biomarkers ; Humans ; Nicotine ; Smoking/genetics ; Tobacco Products ; Tobacco Use Disorder/genetics
    Chemical Substances Biomarkers ; Nicotine (6M3C89ZY6R)
    Language English
    Publishing date 2021-07-27
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1452315-2
    ISSN 1469-994X ; 1462-2203
    ISSN (online) 1469-994X
    ISSN 1462-2203
    DOI 10.1093/ntr/ntab124
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  6. Article ; Online: Isotope Dilution nanoLC/ESI

    Sangaraju, Dewakar / Boldry, Emily J / Patel, Yesha M / Walker, Vernon / Stepanov, Irina / Stram, Daniel / Hatsukami, Dorothy / Tretyakova, Natalia

    Chemical research in toxicology

    2017  Volume 30, Issue 2, Page(s) 678–688

    Abstract: 1,3-Butadiene (BD) is an important industrial and environmental chemical classified as a known human carcinogen. Occupational exposure to BD in the polymer and monomer industries is associated with an increased incidence of lymphoma. BD is present in ... ...

    Abstract 1,3-Butadiene (BD) is an important industrial and environmental chemical classified as a known human carcinogen. Occupational exposure to BD in the polymer and monomer industries is associated with an increased incidence of lymphoma. BD is present in automobile exhaust, cigarette smoke, and forest fires, raising concern about potential exposure of the general population to this carcinogen. Following inhalation exposure, BD is bioactivated to 3,4-epoxy-1-butene (EB). If not detoxified, EB is capable of modifying guanine and adenine bases of DNA to form nucleobase adducts, which interfere with accurate DNA replication and cause cancer-initiating mutations. We have developed a nanoLC/ESI
    MeSH term(s) Animals ; Biomarkers/urine ; Butadienes/toxicity ; Chromatography, High Pressure Liquid ; Ethnic Groups ; Guanine/urine ; Humans ; Indicator Dilution Techniques ; Mass Spectrometry/methods ; Rats ; Rats, Inbred F344 ; Reproducibility of Results ; Spectrometry, Mass, Electrospray Ionization/methods
    Chemical Substances Biomarkers ; Butadienes ; N-7-(1-hydroxy-3-buten-2-yl)guanine ; Guanine (5Z93L87A1R) ; 1,3-butadiene (JSD5FGP5VD)
    Language English
    Publishing date 2017-02-20
    Publishing country United States
    Document type Journal Article ; Validation Studies
    ZDB-ID 639353-6
    ISSN 1520-5010 ; 0893-228X
    ISSN (online) 1520-5010
    ISSN 0893-228X
    DOI 10.1021/acs.chemrestox.6b00407
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: The Impact of Risk-Based Care on Early Childhood and Youth Populations.

    Watanabe, Marisa K / Hostetler, Josih T / Patel, Yesha M / Vergel de Dios, Jessica M / Bernardo, Marc A / Foley, Mary E

    Journal of the California Dental Association

    2016  Volume 44, Issue 6, Page(s) 367–377

    Abstract: This quality improvement project explored dental caries risk among children residing in El Monte, Calif., a low-income area 16 miles east of Los Angeles. In an attempt to decrease oral health disparities, Western University of Health Sciences, College of ...

    Abstract This quality improvement project explored dental caries risk among children residing in El Monte, Calif., a low-income area 16 miles east of Los Angeles. In an attempt to decrease oral health disparities, Western University of Health Sciences, College of Dental Medicine established school-based oral health centers in El Monte and implemented a modified caries risk assessment protocol. Results showed a statistically significant decrease in caries risk following disease management interventions.
    MeSH term(s) Adolescent ; California ; Cariostatic Agents/therapeutic use ; Child ; Child Health ; Child, Preschool ; Cohort Studies ; Dental Care for Children ; Dental Caries/prevention & control ; Dental Caries Susceptibility ; Electronic Health Records ; Feeding Behavior ; Female ; Fluorides, Topical/therapeutic use ; Health Status Disparities ; Humans ; Infant ; Male ; Motivational Interviewing ; Oral Health ; Oral Hygiene/education ; Poverty ; Quality Improvement ; Retrospective Studies ; Risk Assessment ; School Dentistry ; Vulnerable Populations ; Young Adult
    Chemical Substances Cariostatic Agents ; Fluorides, Topical
    Language English
    Publishing date 2016-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2080445-3
    ISSN 1043-2256 ; 0746-424X
    ISSN 1043-2256 ; 0746-424X
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Genetic determinants of CYP2A6 activity across racial/ethnic groups with different risks of lung cancer and effect on their smoking intensity.

    Park, Sungshim L / Tiirikainen, Maarit I / Patel, Yesha M / Wilkens, Lynne R / Stram, Daniel O / Le Marchand, Loic / Murphy, Sharon E

    Carcinogenesis

    2016  Volume 37, Issue 3, Page(s) 269–279

    Abstract: Genetic variation in cytochrome P450 2A6 (CYP2A6) gene is the primary contributor to the intraindividual and interindividual differences in nicotine metabolism and has been found to influence smoking intensity. However, no study has evaluated the ... ...

    Abstract Genetic variation in cytochrome P450 2A6 (CYP2A6) gene is the primary contributor to the intraindividual and interindividual differences in nicotine metabolism and has been found to influence smoking intensity. However, no study has evaluated the relationship between CYP2A6 genetic variants and the CYP2A6 activity ratio (total 3-hydroxycotinine/cotinine) and their influence on smoking intensity [total nicotine equivalents (TNE)], across five racial/ethnic groups found to have disparate rates of lung cancer. This study genotyped 10 known functional CYP2A6 genetic or copy number variants in 2115 current smokers from the multiethnic cohort study [African Americans (AA) = 350, Native Hawaiians (NH) = 288, Whites = 413, Latinos (LA) = 437 and Japanese Americans (JA) = 627] to conduct such an investigation. Here, we found that LA had the highest CYP2A6 activity followed by Whites, AA, NH and JA, who had the lowest levels. Adjusting for age, sex, race/ethnicity and body mass index, we found that CYP2A6 diplotypes were predictive of TNE levels, particularly in AA and JA (P trend < 0.0001). However, only in JA did the association remain after accounting for cigarettes per day. Also, it is only in this population that the lower activity ratio supports lower TNE levels, carcinogen exposure and thereby lower risk of lung cancer. Despite the association between nicotine metabolism (CYP2A6 activity phenotype and diplotypes) and smoking intensity (TNE), CYP2A6 levels did not correlate with the higher TNE levels found in AA nor the lower TNE levels found in LA, suggesting that other factors may influence smoking dose in these populations. Therefore, further study in these populations is recommended.
    MeSH term(s) Adult ; Aged ; Chromatography, Liquid ; Cohort Studies ; Cytochrome P-450 CYP2A6/genetics ; Ethnic Groups/genetics ; Female ; Genetic Variation ; Genotype ; Humans ; Lung Neoplasms/ethnology ; Lung Neoplasms/etiology ; Lung Neoplasms/genetics ; Male ; Mass Spectrometry ; Middle Aged ; Nicotine/metabolism ; Oligonucleotide Array Sequence Analysis ; Risk Factors ; Smoking/adverse effects ; Smoking/genetics
    Chemical Substances Nicotine (6M3C89ZY6R) ; CYP2A6 protein, human (EC 1.14.14.1) ; Cytochrome P-450 CYP2A6 (EC 1.14.14.1)
    Language English
    Publishing date 2016-03
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 603134-1
    ISSN 1460-2180 ; 0143-3334
    ISSN (online) 1460-2180
    ISSN 0143-3334
    DOI 10.1093/carcin/bgw012
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  9. Article ; Online: Benzene Uptake and Glutathione S-transferase T1 Status as Determinants of S-Phenylmercapturic Acid in Cigarette Smokers in the Multiethnic Cohort.

    Haiman, Christopher A / Patel, Yesha M / Stram, Daniel O / Carmella, Steven G / Chen, Menglan / Wilkens, Lynne R / Le Marchand, Loic / Hecht, Stephen S

    PloS one

    2016  Volume 11, Issue 3, Page(s) e0150641

    Abstract: Research from the Multiethnic Cohort (MEC) demonstrated that, for the same quantity of cigarette smoking, African Americans and Native Hawaiians have a higher lung cancer risk than Whites, while Latinos and Japanese Americans are less susceptible. We ... ...

    Abstract Research from the Multiethnic Cohort (MEC) demonstrated that, for the same quantity of cigarette smoking, African Americans and Native Hawaiians have a higher lung cancer risk than Whites, while Latinos and Japanese Americans are less susceptible. We collected urine samples from 2,239 cigarette smokers from five different ethnic groups in the MEC and analyzed each sample for S-phenylmercapturic acid (SPMA), a specific biomarker of benzene uptake. African Americans had significantly higher (geometric mean [SE] 3.69 [0.2], p<0.005) SPMA/ml urine than Whites (2.67 [0.13]) while Japanese Americans had significantly lower levels than Whites (1.65 [0.07], p<0.005). SPMA levels in Native Hawaiians and Latinos were not significantly different from those of Whites. We also conducted a genome-wide association study in search of genetic risk factors related to benzene exposure. The glutathione S-transferase T1 (GSTT1) deletion explained between 14.2-31.6% (p = 5.4x10-157) and the GSTM1 deletion explained between 0.2%-2.4% of the variance (p = 1.1x10-9) of SPMA levels in these populations. Ethnic differences in levels of SPMA remained strong even after controlling for the effects of these two deletions. These results demonstrate the powerful effect of GSTT1 status on SPMA levels in urine and show that uptake of benzene in African American, White, and Japanese American cigarette smokers is consistent with their lung cancer risk in the MEC. While benzene is not generally considered a cause of lung cancer, its metabolite SPMA could be a biomarker for other volatile lung carcinogens in cigarette smoke.
    MeSH term(s) Acetylcysteine/analogs & derivatives ; Acetylcysteine/metabolism ; Aged ; Benzene/metabolism ; Female ; Genome-Wide Association Study ; Genotype ; Glutathione Transferase/metabolism ; Humans ; Male ; Middle Aged ; Quality Control ; Risk Factors ; Smoking/metabolism
    Chemical Substances S-phenyl-N-acetylcysteine (4775-80-8) ; glutathione S-transferase T1 (EC 2.5.1.-) ; Glutathione Transferase (EC 2.5.1.18) ; Benzene (J64922108F) ; Acetylcysteine (WYQ7N0BPYC)
    Language English
    Publishing date 2016-03-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0150641
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  10. Article ; Online: Association of internal smoking dose with blood DNA methylation in three racial/ethnic populations.

    Park, Sungshim L / Patel, Yesha M / Loo, Lenora W M / Mullen, Daniel J / Offringa, Ite A / Maunakea, Alika / Stram, Daniel O / Siegmund, Kimberly / Murphy, Sharon E / Tiirikainen, Maarit / Le Marchand, Loïc

    Clinical epigenetics

    2018  Volume 10, Issue 1, Page(s) 110

    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 ... ...

    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 β 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.
    MeSH term(s) Adult ; Aged ; Asian/genetics ; CpG Islands ; DNA Methylation ; Epigenesis, Genetic ; Female ; Genome-Wide Association Study/methods ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Middle Aged ; Native Hawaiian or Other Pacific Islander/genetics ; Nicotine/urine ; Sequence Analysis, DNA ; Smoking/ethnology ; Smoking/genetics ; Smoking/urine ; United States/ethnology ; White People/genetics
    Chemical Substances Nicotine (6M3C89ZY6R)
    Language English
    Publishing date 2018-08-23
    Publishing country Germany
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553921-8
    ISSN 1868-7083 ; 1868-7075
    ISSN (online) 1868-7083
    ISSN 1868-7075
    DOI 10.1186/s13148-018-0543-7
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