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  • Exploring the epigenetic impact of smoking across racial and ethnic groups

    Exploring the epigenetic impact of smoking across racial and ethnic groups

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    Smoking changes the way genes are expressed, which later contributes to the development of lung cancer and other smoking-related illnesses. But the link between epigenetics (the study of mechanisms that impact gene expression) and smoking is not fully understood, especially in terms of differences across racial and ethnic groups.

    We know that smoking affects people differently based on their race and ethnicity, but identifying epigenetic signatures of smoking would help us better predict risk for smoking-related diseases.”


    Brian Huang, PhD, assistant professor, Department of population and public health sciences, Keck School of Medicine of USC and first author of the new study

    In a National Institutes of Health-funded effort, researchers from the Keck School of Medicine analyzed the link between smoking and DNA methylation, a specific type of epigenetic change that can alter a number of biological processes. The study included data from 2,728 people across six distinct racial and ethnic groups. Researchers found 408 DNA methylation markers (known as “CpG sites”) related to smoking, including two that differed depending on race or ethnicity. The results were published in the American Journal of Human Genetics.

    Most past research on smoking and epigenetics has looked at just one or two racial groups at a time, making the new effort one of the largest multiethnic studies yet. In addition, the researchers quantified smoking by calculating participants’ total nicotine equivalents (TNEs), a biological measure of nicotine uptake that measures levels of nicotine and several other metabolites of cigarette smoke with a urine sample. That enabled a more accurate calculation of smoking dose compared to much of the existing research, which relies on self-reported measures.

    “This study gives us some additional information about the mechanism by which smoking can affect health, and how that could differ across various populations,” Huang said. “Ultimately, that can lead to better prediction, early detection and treatment for smoking-related conditions.”

    Insights from the epigenome

    The research team conducted their primary analysis using data from the Multiethnic Cohort Study, a collaboration between USC and the University of Hawaii that includes African Americans, European Americans, Japanese Americans, Latinos and Native Hawaiians. Using biological samples from 1,994 participants, the researchers determined each person’s smoking dose (by measuring TNEs), as well as the levels of DNA methylation at CpG sites across the genome (through an epigenome-wide association study, or EWAS).

    Across the epigenome, smoking was linked to DNA methylation at 408 sites. That total includes 45 new sites that were not identified in previous studies that relied on self-reports of smoking behavior.

    “This gives us an indication that TNEs can provide more information beyond what we already know from self-reported measures of smoking,” Huang said.

    Of the 408 sites identified, two carried a significant risk difference depending on race or ethnicity. One site on the gene CYTH1 only showed changes in African American people who smoked; another site on MYO1G was more strongly linked with epigenetic changes in Latinos who smoked, compared to other racial and ethnic groups. Those genes perform functions that relate to cancer progression and other disease processes.

    The new insights could improve scientists’ understanding of why some populations face a higher lung cancer risk than others, Huang said. African Americans who smoke face a higher risk of lung cancer than non-Hispanic whites who smoke, while people of Hispanic origin may face a lower risk.

    To further confirm their findings, Huang and his team collected TNE and DNA methylation data from two other groups of participants: 340 people in the Singapore Chinese Health Study and 394 people in the Southern Community Cohort Study. The researchers identified many of the same CpG sites found in the Multiethnic Cohort Study, including the sites most strongly associated with TNEs. That provides evidence that the strongest epigenetic markers of smoking are consistent across multiple racial and ethnic groups, Huang said.

    Better prediction of disease risk

    In their next study, the researchers will conduct an EWAS of DNA methylation and lung cancer risk: How do epigenetic changes increase a person’s risk for lung cancer?

    “By conducting these joint studies, we can understand the mechanism by which DNA methylation acts as a mediator between smoking and lung cancer, which can in turn improve our ability to predict lung cancer risk,” Huang said.

    He and his team also have research underway to study epigenetic changes associated with additional biomarkers of smoking, including biological levels of cadmium, a heavy metal found in cigarette smoke.

    About this research

    In addition to Huang, the study’s other authors are Yesha Patel, Christopher Haiman, Kimberly Siegmund and Daniel Stram from the Department of Population and Public Health Sciences, Keck School of Medicine of USC; Alexandra Binder, Brandon Quon, Annette Lum-Jones, Maarit Tiirikainen, Lenora Loo, Lynne Wilkens, Loïc Le Marchand and Sungshim L. Park from the University of Hawaii Cancer Center; Sharon Murphy and Stephen Hecht from the Masonic Cancer Center, University of Minnesota; Alika Maunakea from the John. A. Burns School of Medicine, University of Hawaii; Woon-Puay Koh from the National University of Singapore; Woon-Puay Koh, William Blot and Melinda Aldrich from the Vanderbilt University Medical Center; and Jian-Min Yuan from the University of Pittsburgh.

    This work was supported by the National Institutes of Health/National Cancer Institute (NIH/NCI) [P01CA138338]. NIH also supported the Multiethnic Cohort Study [U01CA164973], the Singapore Chinese Health Study [R01CA129534, R01CA144034, UM1CA182876] and the Southern Community Cohort Study [U01CA202979, R01CA092447].

    Source:

    Keck School of Medicine of USC

    Journal reference:

    Huang, B. Z., et al. (2024). Epigenome-wide association study of total nicotine equivalents in multiethnic current smokers from three prospective cohorts. The American Journal of Human Genetics. doi.org/10.1016/j.ajhg.2024.01.012.

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  • UCL study highlights misconceptions about vaping risks among English smokers

    UCL study highlights misconceptions about vaping risks among English smokers

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    More than half of smokers in England wrongly believe that vaping is more harmful or as harmful as smoking, according to a new study led by UCL (University College London) researchers.

    The study, published in the journal JAMA Network Open and funded by Cancer Research UK, looked at survey responses from 28,393 smokers in England between 2014 and 2023.

    The research team found that public perceptions of e-cigarettes had worsened considerably over the past decade, with an overall increase in the perceived harm of e-cigarettes since 2021, coinciding with a sharp rise in vaping among young people.

    In June 2023, 57% of respondents said they thought vaping was equally as harmful as smoking or more harmful, while only 27% thought e-cigarettes were less harmful.

    These findings have important implications for public health. The risks of vaping are much lower than the risks of smoking and this isn’t being clearly communicated to people.


    This misperception is a health risk in and of itself, as it may discourage smokers from substantially reducing their harm by switching to e-cigarettes. It may also encourage some young people who use e-cigarettes to take up smoking for the first time, if they believe the harms are comparable.


    Better communication about the health risks is needed so that adults who smoke can make informed choices about the nicotine products they use.”


    Dr Sarah Jackson, Lead Author, UCL Institute of Epidemiology & Health Care

    The researchers used data from the Smoking Toolkit Study, in which a different sample of approximately 1,700 adults in England (who are representative of the population) are interviewed each month.

    In 2014, the study showed, public perceptions of e-cigarettes were more favorable, with 44% of smokers regarding them as less harmful than cigarettes, and only 11% saying e-cigarettes were more harmful (this doubled to 23% by 2023).

    The perception of e-cigarettes’ harm worsened sharply in late 2019 and early 2020, coinciding with an outbreak of acute lung injuries in the United States that was wrongly linked to nicotine e-cigarettes (the EVALI outbreak) but later attributed to illicit cannabis vaping products containing vitamin E acetate.

    Though perceptions had recovered by late 2020, they declined again from 2021 through to 2023 amid growing concern about youth vaping, as large numbers of young people starting to use disposable e-cigarettes.

    By 2023, only 19% of smokers who did not vape said they thought vaping was less harmful than smoking.

    The rise in the proportion who said e-cigarettes were more harmful than cigarettes was most pronounced among those aged under 35, despite use of e-cigarettes being much more common in this age group.

    Senior author Professor Jamie Brown (UCL Institute of Epidemiology & Health Care) said: “E-cigarettes are novel and so have attracted much attention in the media, with news articles often overstating their risks to health compared with smoking. There is relatively little reporting about deaths caused by smoking, even though 75,000 people die as a result of it in England each year.

    “The Government plans to offer one million smokers a free vaping starter kit alongside behavioral support to help them quit. This initiative may be undermined if many smokers are unwilling to try e-cigarettes because they wrongly believe them to be just as harmful as cigarettes or more so.”

    In its online guidance*, the NHS says: “Cigarettes release thousands of different chemicals when they burn. Many are poisonous and up to 70 cause cancer. They also cause other serious illnesses, including lung disease, heart disease and stroke. Most of the harmful chemicals in tobacco smoke, including tar and carbon monoxide, are not contained in vape aerosol.”

    Source:

    University College London

    Journal reference:

    Jackson, S. E., et al. (2024). Trends in Harm Perceptions of E-Cigarettes vs Cigarettes Among Adults Who Smoke in England, 2014-2023. JAMA Network Open. doi.org/10.1001/jamanetworkopen.2024.0582.

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  • Study reveals low omega-3 intake among pregnant women despite health benefits

    Study reveals low omega-3 intake among pregnant women despite health benefits

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    Results from a new nationwide cohort study show that, despite strong recommendations in favor of consuming omega-3 fatty acids for optimal pregnancy outcomes and offspring health, 25% of participants reported rarely, or never eating fish during pregnancy, with fewer taking omega-3 supplements.

    The study, “Demographic and health characteristics associated with fish and n-3 fatty acid supplement intake during pregnancy: results from pregnancy cohorts in the ECHO program” was led by investigators at the Harvard Pilgrim Health Care Institute and published February 27 in Public Health Nutrition. The study is timely, arriving as the World Health Organization and U.S. National Academies both plan to issue reports on the risks and benefits of fish consumption in pregnancy later this year.

    Omega-3 fatty acids are essential nutrients for supporting positive health outcomes. Getting enough of these nutrients during pregnancy is vital for preventing preterm birth and promoting optimal child health and neurodevelopment.”


    Emily Oken, study’s lead author, Harvard Medical School professor and chair of the Department of Population Medicine at the Harvard Pilgrim Health Care Institute

    Prior research looking at the demographic characteristics associated with fish and supplement intake during pregnancy has been limited, involving fewer participants and older data that may not represent current intake. The study team addressed this research gap using information on fish consumption reported by 10,800 pregnant women, and supplement intake information from 12,646 pregnant women from cohorts across the U.S. participating in the Environmental influences on Child Health Outcomes (ECHO) program.

    Study results showed that nearly 25% of participants reported not eating fish or eating it less than once per month, and only 16% took supplements. Contrary to expectations, supplement use was less common among those who consumed less fish, putting that group at even higher risk for insufficient omega-3 fatty acid intake. Similar to supplement use, older participants with a higher income and education consumed more fish. However, unlike supplements, fish consumption was higher in those with racial/ethnic identities other than non-Hispanic White and in those who used tobacco and nicotine products. The highest likelihood of supplement intake was among those who were older, had a higher education and income, and were non-Hispanic White or Asian. Additionally, supplement use was less common among those at higher risk for adverse pregnancy outcomes as a function of using tobacco or nicotine products or having a higher BMI.

    “Current evidence shows that the benefits of maternal consumption of low-mercury fish, or in its place, omega-3 supplements, outweigh any potential risks,” says Dr. Oken. “Our study provides updated information to inform much needed public health advice and resources to support clinical conversations to encourage consumption of low-mercury fish during pregnancy and intake of omega-3 supplements among those who do not consume fish.”

    Source:

    Harvard Pilgrim Health Care Institute

    Journal reference:

    Oken, E., et al. (2024) Demographic and health characteristics associated with fish and n-3 fatty acid supplement intake during pregnancy: results from pregnancy cohorts in the ECHO program. Public Health Nutrition. doi.org/10.1017/S136898002400051X

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  • Vaping increases susceptibility to COVID-19 infection, study finds

    Vaping increases susceptibility to COVID-19 infection, study finds

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    Vapers are susceptible to infection by SARS-CoV-2, the virus that spreads COVID-19 and continues to infect people around the world, a University of California, Riverside, study has found.

    The liquid used in electronic cigarettes, called e-liquid, typically contains nicotine, propylene glycol, vegetable glycerin, and flavor chemicals. The researchers found propylene glycol/vegetable glycerin alone or along with nicotine enhanced COVID-19 infection through different mechanisms.

    Study results appear in the American Journal of Physiology.

    The researchers also found that the addition of benzoic acid to e-liquids prevents the infection caused by propylene glycol, vegetable glycerin, and nicotine. 

    Users who vape aerosols produced from propylene glycol/vegetable glycerin alone or e-liquids with a neutral to basic pH are more likely to be infected by the virus, while users who vape aerosols made from e-liquids with benzoic acid -; an acidic pH -; will have the same viral susceptibility as individuals who do not vape.”


    Rattapol Phandthong, postdoctoral researcher, Department of Molecular, Cell and Systems Biology and research paper’s first author

    The researchers obtained airway stem cells from human donors to produce a 3D tissue model of human bronchial epithelium. They then exposed the tissues to JUUL and BLU electronic cigarette aerosols to study the effect on SARS-CoV-2 infection. They found all tissues showed an increase in the amount of ACE2, a host cell receptor for the SARS-CoV-2 virus. Further, TMPRSS2, an enzyme essential for the virus to infect cells, was found to show increased activity in tissues exposed to aerosols with nicotine.

    Prue Talbot, a professor of the graduate division and Phandthong’s advisor, said e-cigarette users should be cautious about vaping as some products will increase their susceptibility to SARs-CoV-2 infection. 

    “It would probably be best for vapers to quit vaping for the protection of their health and to stop nicotine dependency,” she said. “If they cannot stop vaping, it is better to vape aerosols produced from an e-liquid with acidic pH or with benzoic acid to prevent the enhanced SARS-CoV-2 infection caused by nicotine, propylene glycol, and vegetable glycerin. However, inhalation of benzoic acid has its own risk, and data is still limited on this topic.”

    The researchers acknowledge that the relationship between e-cigarettes and SARS-CoV-2 susceptibility is complex.

    “The complexity is attributed to a wide range of available e-liquids, the chemical composition of each e-liquid, and different models of e-cigarettes,” Phandthong said. “Our study only used Classic Tobacco Flavor JUUL e-cigarette and BLU Classic Tobacco e-cigarette. Even with just these two e-cigarettes, we found the aerosols and individual ingredients produced different effects on SARS-CoV-2 infection.” 

    Phandthong and Talbot hope the Food and Drug Administration will use their findings to implement regulatory laws on e-cigarette products.

    “Our findings could also help improve the design of clinical trials involving the use of tobacco products and SARS-CoV-2 infection,” Phandthong said. “In the meantime, it is worth bearing in mind that the scientific literature has shown that a vaper who contracted SARS-CoV-2 has more complications during the recovery period and is more likely to develop long COVID-19, which can be serious and last many months post-infection. We hope our findings encourage vapers to stop vaping and discourage non-users from starting to vape.”

    Phandthong acknowledged the team only investigated the initial stage of SARS-CoV-2 infection. 

    “There are many later stages involved in infection, such as viral replication,” he said. “It is likely that these additional stages can also be affected by inhalation of e-cigarette aerosols.” 

    Phandthong and Talbot were joined in the study by Man Wong, Ann Song, and Teresa Martinez.

    The research was funded by grants from the Tobacco-Related Disease Research Program, National Institute of Environmental Health Sciences, Center for Tobacco Products of the Food and Drug Administration, and California Institute of Regenerative Medicine.

    Source:

    University of California – Riverside

    Journal reference:

    Phandthong, R., et al. (2023). Does Vaping Increase the Likelihood of SARS-CoV-2 Infection? Paradoxically Yes and No. American Journal of Physiology-Lung Cellular and Molecular Physiology. doi.org/10.1152/ajplung.00300.2022.

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