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PURPOSE: Although lung cancer is one of the most common malignancies, the underlying genetics regarding susceptibility remain poorly understood. We characterized the spectrum of pathogenic/likely pathogenic (P/LP) germline variants within DNA damage response (DDR) genes among lung cancer cases and controls in non-Hispanic Whites (NHWs) and African Americans (AAs). MATERIALS AND METHODS: Rare, germline variants in 67 DDR genes with evidence of pathogenicity were identified using the ClinVar database. These P/LP variants were genotyped in a sample of 3,040 lung cancer cases and controls from the Inflammation, Health, Ancestry, and Lung Epidemiology study (NHW: n = 1,915; AA: n = 1,125) and were tested for their association with lung cancer using multivariate logistic regression adjusting for age, sex, pack-years, and race. RESULTS: We identified 49 unique rare P/LP variants in 21 genes among 156 carriers. Approximately 5.9% of lung cancer cases and 4.2% of controls carried at least one P/LP variant. P/LP variants in DDR genes were more common in lung cancer cases, particularly those diagnosed with adenocarcinoma (odds ratio [OR], 1.46 [95% CI, 1.00 to 2.14]). MUTYH variants were associated with lung cancer overall (OR, 1.82 [95% CI, 1.10 to 3.12]), with the strongest associations among never smokers (OR, 3.37 [95% CI, 1.08 to 10.26]), and in individuals who do not meet current USPSTF screening criteria (OR, 2.85 [95% CI, 1.20 to 7.53]). CONCLUSION: Germline variants in DDR genes appear to be associated with lung cancer, particularly when examined by gene subtype and morphologic subtype. MUTYH , a gene historically associated with colorectal and other GI malignancies, emerged as a candidate gene that should be examined in individuals who do not have a significant smoking history. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies of cancer survivors have predominantly focused on non‐Hispanic White, elderly patients, despite the observation that African Americans have higher rates of mortality. Therefore, we characterized cancer survivorship in younger African American survivors using the Detroit Research on Cancer Survivors (ROCS) study to assess health behaviors and quality of life. Methods: Five hundred and seventeen patients diagnosed with any cancer between the ages of 20–49 (mean age: 42 years; SD: 6.7 years) completed a survey to identify important clinical, behavioral, and sociodemographic characteristics, measures of health literacy, and experiences of discrimination. Quality of life outcomes were evaluated in patients using FACT‐G, FACT‐Cog, and PROMIS® Anxiety and Depression scales. Stepwise linear and logistic regression were used to assess the association between quality of life measures and participant characteristics. Results: The mean FACT‐G score was 74.1 (SD: 21.3), while the FACT‐Cog was 55.1 (SD: 17.1) (FACT‐G range 0–108 with higher scores indicating better function; elderly cancer patient mean: 82.2; FACT‐Cog 18‐item range 0–72 points with higher scores indicating better perceived cognitive functioning; scores <54 indicating cognitive impairment). In addition, 27.1% and 21.6% of patients had a score indicative of moderate or severe anxiety and depression, respectively. Perceived discrimination and the number of discriminatory events were significantly associated with reductions in three of the four quality of life measures. Health literacy was positively associated with all four health measures, while total comorbidity count was negatively associated with three of the four measures. Conclusion: Younger adult African American cancer survivors who report experiencing discrimination and suffer from multiple comorbid conditions have poorer mental and overall health. Understanding the unique clinical and socioeconomic stressors that influence this patient population is essential for reducing health disparities and improving long‐term survivorship. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID‐19) has had profound effects on population health to date. African American cancer survivors are particularly vulnerable to developing severe consequences; therefore, understanding the impact of the virus on this patient population is critical. Methods: The Detroit Research on Cancer Survivors cohort is a unique effort to understand the determinants of poor outcomes in African American cancer survivors. To date, more than 4500 cancer survivors and nearly 950 primary caregivers have been enrolled; participation includes a survey and the collection of biospecimens, medical records, and tumor tissue. Beginning in the spring of 2020, a supplemental survey focusing on the impact of COVID‐19 was offered to enrolled participants. The analysis included 890 survivors. Results: Nearly all survivors (>99%) reported changes in their daily activities in an effort to reduce the risk of infection. More than 40% of the survivors reported some disruption in their access to medical care. A substantial proportion of the survivors (>40%) reported feeling anxious, depressed, and/or isolated during the COVID‐19 pandemic. Approximately 40% of the patients reported changes in health behaviors shown to negatively affect survivorship outcomes (physical inactivity, smoking, and alcohol use) as a result of the pandemic. Conclusions: The influence of the COVID‐19 pandemic on African American cancer survivors is substantial: it has affected both their physical and mental health. Coupled with changes in health behaviors, these factors will likely affect outcomes in this high‐risk patient population, and this makes further study and interventions necessary to mitigate the long‐term impact of the pandemic on cancer outcomes. The COVID‐19 pandemic has had a profound impact on the physical and mental health of African American cancer survivors living in Detroit, Michigan. Strategies focusing on health behaviors such as physical activity would improve patient health and quality of life. [ABSTRACT FROM AUTHOR]

Genome‐wide association studies (GWAS) have identified several loci contributing to lung cancer and COPD risk independently; however, inflammation‐related pathways likely harbor additional lung cancer risk‐associated variants in biologically relevant immune genes that differ dependent on COPD. We selected single nucleotide polymorphisms (SNPs) proximal to 2,069 genes within 48 immune pathways. We modeled the contribution of these variants to lung cancer risk in a discovery sample of 1,932 lung cancer cases and controls stratified by COPD status and validation sample of 953 cases and controls also stratified by COPD. There were 43 validated SNPs in those with COPD and 60 SNPs in those without COPD associated with lung cancer risk. Furthermore, 29 of 43 and 28 of 60 SNPs demonstrated a statistically significant interaction with COPD in the pooled sample. These variants demonstrated tissue‐dependent effects on proximal gene expression, enhanced network connectivity and resided together in specific immune pathways. These results reveal that key inflammatory related genes and pathways, not found in prior GWAS, impact lung cancer risk in a COPD‐dependent manner. Genetic variation identified in our study supplements prior lung cancer GWAS and serves as a foundation to further interrogate risk relationships in smoking and COPD populations. What's new? Former smokers may have lingering inflammation as a result of smoking, and this inflammation may be the reason that people with COPD have a 2‐ to 3‐fold increased risk of lung cancer. Here the authors looked at a high‐density, multiethnic SNP array to find variants linked to lung cancer risk which occur in genes involved in immune pathways. They found 43 SNPs associated with lung cancer in people with COPD, and 29 of the 43 showed significant biological interaction with COPD. This is the first study to identify SNPs that contribute to lung cancer risk in a COPD‐dependent fashion. [ABSTRACT FROM AUTHOR]

Background: African Americans have higher incidence and mortality from lung cancer than non-Hispanic Whites, but investigations into differences in immune response have been minimal. Therefore, we compared components of the tumor microenvironment among African Americans and non-Hispanic Whites diagnosed with non-small cell lung cancer based on PDL1 or tertiary lymphoid structure (TLS) status to identify differences of translational relevance., Methods: Using a cohort of 280 patients with non-small cell lung cancer from the Inflammation, Health, Ancestry, and Lung Epidemiology study (non-Hispanic White: n = 155; African American: n = 125), we evaluated PDL1 tumor proportion score (<1% vs. ≥1%) and TLS status (presence/absence), comparing differences within the tumor microenvironment based on immune cell distribution and differential expression of genes., Results: Tumors from African Americans had a higher proportion of plasma cell signatures within the tumor microenvironment than non-Hispanic Whites. In addition, gene expression patterns in African American PDL1-positive samples suggest that these tumors contained greater numbers of γδ T cells and resting dendritic cells, along with fewer CD8+ T cells after adjusting for age, sex, pack-years, stage, and histology. Investigation of differential expression of B cell/plasma cell-related genes between the two patient populations revealed that two immunoglobulin genes (IGKV2-29 and IGLL5) were associated with decreased mortality risk in African Americans., Conclusions: In the first known race-stratified analysis of tumor microenvironment components in lung cancer based on PDL1 expression or TLS status, differences within the immune cell composition and transcriptomic signature were identified that may have therapeutic implications., Impact: Future investigation of racial variation within the tumor microenvironment may help direct the use of immunotherapy., (©2024 American Association for Cancer Research.)