Lung cancer early detection and health disparities: the intersection of epigenetics and ethnicity

Abstract

Lung cancer is the most prominent cause of cancer-related mortality. Significant disparities in incidence and outcome characterize the disease's manifestations among ethnically and racially diverse populations. Complete surgical resection is the most effective curative treatment. However, success relies on early tumor detection. The National Lung Cancer Screening trial showed that lung cancer related mortality can be reduced by the use of low-dose CT (LDCT) screening. However, this test is plagued by a high false positive rate of 97% and the device itself is limited to designated cancer centers due to its expense and size. This restriction makes it difficult for underserved groups to access LDCT screening, the current standard of care. Highly sensitive and specific epigenetic DNA methylation-based biomarkers have the potential to work independently or in conjunction with LDCT screening to identify early-stage tumors. These tests could reduce unnecessary invasive confirmatory diagnostic tests and their associated morbidity and mortality.These tests also have the opportunity to bring lung cancer screening to the community thereby reducing unequal accessibility. However, epigenetic alterations are closely linked to the interplay between hereditary and environmental factors such as diet, lifestyle, ethnic ancestry, toxin exposure, residential segregation, and disparate community support structures. Despite this, the overwhelming number of early detection DNA methylation biomarker studies to date have either failed to control for ethnicity or have employed heavily Caucasian-biased patient cohorts. This review seeks to summarize the literature related to the early detection of lung cancer through molecular biomarkers among different ethnicities. Ethnical specific epigenetic biomarkers have the potential to be the first step towards an accessible, available personalized medicine approach to cancer through liquid biopsy.

The Association BetweenVDRandGCPolymorphisms and Lung Cancer Risk: A Systematic Review and Meta-Analysis

“…For example, Fu et al (2014) showed that the VDR Bsm1 polymorphism played a protective role in the lung carcinogenesis, while Zhong et al (2014) found that B allele and bb genotype were associated with lung cancer risk in overall populations. Furthermore, lung cancer rates and trends vary substantially by sex, age, race/ethnicity, socioeconomic status, and geography (de Groot et al, 2018;Lerner et al, 2018). Genetic and environmental factors may also influence the VDR and GC plasma concentrations and functions (Wilson et al, 2015).…”

Lung Cancer Screening and Epigenetics in African Americans: The Role of the Socioecological Framework

“…While it is likely that most pathways may remain consistent between groups, it is possible that exposure and access to different factors, including different biological, environmental, and socioeconomic conditions, may contribute to differential epigenetic changes, leading to racial disparities in lung cancer outcomes among AAs ( 39 – 41 ). And yet, specific mechanisms through which how neighborhood conditions may contribute to epigenomic changes and gene expression have been far less explored ( 42 ).…”

“…Recent research in comparative epigenetics in the U.S. reveals a spectrum of promoter methylation across racial/ethnic groups, the body of studies published in the literature about epigenetics in cancer in minority populations is scarce. Many studies often do not indicate race-specific changes in DNA methylation ( 42 , 46 , 47 ). However, there has been progress.…”

Clinical application of quantitative glycomics

“…To date, imaging is still the major diagnostic technique for lung cancer. Although there are some biomarkers such as CEA or CA125, the lack of specificity and sensitivity inhibits their broad uses, thus demanding the need for better biomarkers [124].…”