Home Medizin Erforschung der epigenetischen Auswirkungen des Rauchens auf verschiedene Rassen und ethnische Gruppen

Erforschung der epigenetischen Auswirkungen des Rauchens auf verschiedene Rassen und ethnische Gruppen

von NFI Redaktion

Smoking alters the way genes are expressed, leading to the development of lung cancer and other smoking-related diseases later in life. The relationship between epigenetics (the study of mechanisms that influence gene expression) and smoking is not fully understood, especially in terms of differences between races and ethnic groups.

„We know that smoking affects people differently depending on race and ethnicity, but identifying epigenetic signatures of smoking would help us better predict the risk of smoking-related diseases.“


Brian Huang, PhD, Assistant Professor, Department of Population and Public Health Sciences, Keck School of Medicine at USC and lead author of the new study

In an initiative funded by the National Institutes of Health, researchers at the Keck School of Medicine examined the relationship between smoking and DNA methylation, a specific type of epigenetic change that can alter a variety of biological processes. The study included data from 2,728 individuals from six different races and ethnic groups. Researchers identified 408 DNA methylation markers (known as „CpG sites“) related to smoking, including two that varied depending on race or ethnicity. The findings were published in the American Journal of Human Genetics.

Most previous research on smoking and epigenetics has focused on one or two racial groups, making this new effort one of the largest multiethnic studies to date. Additionally, researchers quantified smoking by calculating the Total Nicotine Equivalents (TNEs) of the participants, a biological measure of nicotine exposure that assesses nicotine levels and several other cigarette smoke metabolites from a urine sample. This allowed for a more accurate assessment of smoking dose compared to much of the existing research that relies on self-reported measures.

„This study provides us with additional information about the mechanism by which smoking can impact health and how this may vary between different populations,“ said Huang. „Ultimately, this could lead to better prediction, early detection, and treatment of smoking-related diseases.“

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 involving African Americans, European Americans, Japanese Americans, Latinos, and Native Hawaiians. Using biological samples from 1,994 participants, the researchers determined the smoking dose of each person (by measuring TNEs) as well as the degree of DNA methylation at CpG sites across the entire genome (through an epigenome-wide association study or EWAS).

Smoking was associated with DNA methylation at 408 sites throughout the epigenome. This total includes 45 new sites not identified in previous studies relying on self-reported smoking behavior.

„This suggests that TNEs may provide more information than we currently know from self-reported smoking measurements,“ said Huang.

Of the 408 identified sites, two showed significant risk differences depending on race or ethnicity. One site on the CYTH1 gene showed changes only in African Americans who smoked, while another site on MYO1G was more strongly associated with epigenetic changes in smoking Latinos compared to other races and ethnic groups. These genes play roles related to cancer progression and other disease processes.

The new findings could enhance scientists‘ understanding of why some populations are at higher risk for lung cancer than others, Huang said. African Americans who smoke have a higher risk of lung cancer than non-Hispanic Whites who smoke, while individuals of Hispanic descent may have a lower risk.

To further validate their results, Huang and his team collected TNE and DNA methylation data from two other participant groups: 340 individuals in the Singapore Chinese Health Study and 394 individuals in the Southern Community Cohort Study. The researchers identified many of the same CpG sites as in the multiethnic cohort study, including sites most strongly associated with TNEs. This is evidence that the strongest epigenetic markers of smoking are consistent across multiple races and ethnic groups, Huang said.

Improving Disease Risk Prediction

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

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

He and his team are also conducting research to examine epigenetic changes associated with additional smoking biomarkers, including the biological concentration of cadmium, a heavy metal found in cigarette smoke.

About this Research

In addition to Huang, the additional authors of the study are Yesha Patel, Christopher Haiman, Kimberly Siegmund, and Daniel Stram from the Department of Population and Public Health Sciences at the Keck School of Medicine at 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 at the 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 at USC

Journal Reference:

Huang, BZ, 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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